bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints
Authors: Jahn Stephan C. , Corsino Patrick E. , Davis Bradley J. , Law Mary E. , Nørgaard Peter , Law Brian K.
Published: January 2013

The cell has many mechanisms for protecting the integrity of its genome. These mechanisms are often weakened or absent in many cancers, leading to high rates of chromosomal instability in tumors. Control of the cell cycle is crucial for the function of these checkpoints, and is frequently lost in cancers as well. Overexpression of Cyclin D1 in a large number of breast cancers causes overactivation of the cyclin-dependent kinases, including Cdk2. Constitutive Cdk2 activation through Cyclin D1 generates tumors in mice that are aneuploid and have many characteristics indicative of chromosomal instability. Expression of these complexes in the MCF10A cell line leads to retinoblastoma protein (Rb) hyperphosphorylation, a subsequent increase in proliferation rate, and increased expression of the spindle assembly checkpoint protein Mad2. This results in a strengthening of the spindle assembly checkpoint and renders cells more sensitive to the spindle poison paclitaxel. Constitutive Rb phosphorylation also causes a weakening of the p53-dependent tetraploidy checkpoint. Cells with overactive Cdk2 fail to arrest after mitotic slippage in the presence of paclitaxel or cytokinesis failure during treatment with cytochalasin-B, generating 8N populations. This additional increase in DNA content appears to further intensify the tetraploidy checkpoint in a step-wise manner. These polyploid cells are not viable long-term, either failing to undergo division or creating daughter cells that are unable to undergo subsequent division. This study raises intriguing questions about the treatment of tumors with overactive Cdk2.
The dynamin-binding domains of Dap160/Intersectin affect bulk membrane retrieval in synapses
Authors: Winther Åsa M. E. , Jiao Wei , Vorontsova Olga , Rees Kathryn A. , Koh Tong-Wey , Sopova Elena , Schulze Karen L. , Bellen Hugo J. , Shupliakov Oleg
Published: January 2013

Dap160/Intersectin interacts with several synaptic proteins and affects endocytosis and synapse development. The functional role of the different protein interaction domains is not well understood. Here we show that Dap160 lacking the dynamin-binding SH3 domains does not affect the development of the neuromuscular junction but plays a key role in synaptic vesicle recycling. dap160 mutants lacking dynamin-interacting domains no longer accumulate dynamin properly at the periactive zone, and it becomes dispersed in the bouton during stimulation. This is accompanied by a reduction in FM1–43 uptake, and an accumulation of large vesicles and membrane invaginations. However, we do not observe an increase in the number of clathrin-coated intermediates. We also note a depression in evoked EJPs during high-rate stimulation, accompanied by aberrantly large minis. The data reveal the important role of Dap160 in the targeting of dynamin to the periactive zone, where it is required to suppress bulk synaptic vesicle membrane retrieval during high frequency activity.
Spatial accuracy of a rapid defense behavior in caterpillars
Authors: van Griethuijsen Linnea I. , Banks Kelly M. , Trimmer Barry A.
Published: January 2013

Aimed movements require that an animal accurately locates the target and correctly reaches that location. One such behavior is the defensive strike seen in Manduca sexta larva. These caterpillars respond to noxious mechanical stimuli applied to their abdomen with a strike of the mandibles towards the location of the stimulus. The accuracy with which the first strike movement reaches the stimulus site depends on the location of the stimulus. Reponses to dorsal stimuli are less accurate than those to ventral stimuli and the mandibles generally land ventral to the stimulus site. Responses to stimuli applied to anterior abdominal segments are less accurate than responses to stimuli applied to more posterior segments and the mandibles generally land posterior to the stimulus site. A trade-off between duration of the strike and radial accuracy is only seen in the anterior stimulus location (body segment A4). The lower accuracy of the responses to anterior and dorsal stimuli can be explained by the morphology of the animal; to reach these areas the caterpillar needs to move its body into a tight curve. Nevertheless, the accuracy is not exact in locations that the animal has shown it can reach, which suggests that consistently aiming more ventral and posterior of the stimulation site might be a defense strategy.
Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution
Authors: Kolb E. M. , Rezende E. L. , Holness L. , Radtke A. , Lee S. K. , Obenaus A. , Garland T.
Published: January 2013

Increased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P<0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.
Reconsideration of the Optically Investigated Competitive Reaction between Cytochrome c Reduction due to Superoxide and Superoxide Dismutation in the Presence of Xanthine Oxidase
Authors: Mitsuta Keiichi
Published: January 2013

Though reported in 1973 by Sawada and Yamazaki, the experimental data obtained from kinetic competition between cytochrome c reduction due to superoxide and spontaneous dismutation of superoxide have long been disregarded because of disagreement with the experimental values obtained from pulse radiolysis. Assuming that the cause of this disagreement could be explained as being an acceleration of the dismutation rate due to the superoxide dismutase (SOD)-like activity possessed by xanthine oxidase (XOD), the value of the rate constant, kXOD, for the reaction between XOD and superoxide that was considered necessary to explain their experimental findings was calculated. As a result, the values of kXOD have been found to be 3.0 × 106 (pH 5), 4.4 × 106 (pH 5.5), 5.5 × 106 (pH 7), 3.6 × 106 (pH 7.8), and 9.2 × 105 (pH 8.5) in M−1 s−1. These values are good matches for two previous experimental values, 2.1 × 106 (pH 7.8) and 8.0 × 105 (pH 12) in M−1 s−1, obtained from the present author’s ESR spin-trapping experiments, and are considered to show the overall image of the SOD-like function acquired by XOD in the long course of its molecular evolution.
Application of Adsorption Microcalorimetry in the Study of Cu(II) Removal Using Magnetic Nanoparticles
Authors: Giraldo Liliana , Moreno-Piraján Juan Carlos
Published: January 2013

The objective of this study was to explain the synthesis of magnetic polymer adsorbent (FePA) nanoparticles coupled with metal-chelating ligands of N-(2-acetamido)iminodiacetic acid (ADA) and their application for the removal of Cu(II) ions. Nanoparticles of magnetite–polyvinyl acetate (denoted as Fe–PVAC) were synthesized by coating Fe3O4 (magnetite) with PVAC and vinyl acetate (VAC). Several sequential procedures were performed, and the coupling property of ADA was subsequently used to introduce functional groups on the surface of the Fe–PVAC nanoparticles. These sequential procedures yielded the following: magnetite–polyvinyl alcohol, nanoparticles of magnetite–polyvinyl propenepoxide and nanoparticles of magnetite–PVAC–ADA (Fe–PVAC–ADA). An example of the application of Fe–PVAC–ADA was explained by adsorbing Cu(II) ions, which can be chelated by the metal-chelating ligands of ADA in aqueous solution. Batch experiments were performed to determine the kinetics and mechanism of Cu(II) adsorption by the Fe–PVAC–ADA nanoparticles. The adsorption of Cu(II) on Fe–PVAC–ADA was monitored by adsorption microcalorimetry.
Applying Combined Langmuir–Freundlich Model to the Multi-Component Adsorption of BTEX and Phenol on Smectite Clay
Authors: Carvalho Marilda N. , de Abreu Cesar A.M. , Benachour Mohand , Sales Deivson C. S. , Baraúna Osmar S. , da Motta Sobrinho Mauricio A.
Published: January 2013

Adsorption using clay is increasingly being applied in the secondary treatment of effluents contaminated with organic compounds discharged from oil industries. This study was aimed at applying a combined Langmuir–Freundlich model to describe the multi-component adsorption of organic compounds such as benzene, toluene, ethylbenzene, xylenes and phenol using smectite clay. The results of the study well fitted with the model developed. In addition, the model parameters suggest that maximum adsorption capacities (qm) can be achieved between 2.45 (toluene) and 22.40 mg g−1 (phenol). The equilibrium points for the compounds were achieved in approximately 20–30 minutes.
Cavity Design via Entrapment of Tetrapyrrole Macrocycles in Sol–Gel Matrices for Catalytic, Optical or Sensoring Functions
Authors: García-Sánchez M.A. , Quiroz-Segoviano R.I.Y. , Rojas F. , Menchaca-Campos E.C. , Tello–Solís S.R. , Munguía-Cortéz L. , Díaz-Alejo L.A. , Salas-Bañales E.
Published: January 2013

The physicochemical and luminescent properties of tetrapyrrole macrocycles, such as the porphyrins (H2P) and phthalocyanines (H2Pc), were preserved by trapping or bonding these species in silica matrices. The method involved used hydroxy-aluminium tetrasulphophthalocyanine OH(Al)TSPc as a probe to find optimal conditions for the entrapment of tetrapyrrole molecules. This methodology made possible the trapping or fixing of macrocyclic species or their respective complexes in the interior of pores existing in monolithic, translucent, normal, or organo-modified silica xerogels. The average pore sizes ranged from 2.0 to 3.6 nm in these systems and depended on the structure, the nature of the cation in the complex and on the identity and position of the substituents at the periphery of the macrocyclic species. Under appropriate conditions, the tetrapyrrolic species can be trapped or bonded to the pore network in stable and monomeric form; however, the interactions with Si–OH groups on the pore walls inhibit the efficient displaying of its properties. To avoid this deleterious effect, some strategies are used, such as to place the macrocycle far from the pore walls through long bridges or by substituting Si–OH groups with alkyl or aryl species. Average pore diameters vary from 3.5 to 9.4 nm when long unions are established between the macrocycle and the pore walls or when more of one macrocyclic species are trapped inside each pore. The spectroscopic properties of the macrocycles trapped in these systems are similar to those displayed by the same species in solution. When phthalocyanines or porphyrins are trapped or bonded to the pore walls of organo-modified silica, the spectroscopic properties are better preserved and their intensities are a function of the chain length of the alkyl group present in the silica matrix. This last result suggests the possibility of tuning the pore size and polarity inside them by choosing the tetrapyrrole species that can be trapped or bonded; in this way, it is possible to create more efficient systems for catalytic, optical, sensoring and medical applications.
Chromatographic Separation of Isomaltooligosaccharides on Ion-Exchange Resins: Effect of the Cationic Form
Authors: Rabelo M.C. , Pereira C.S.M. , Rodrigues S. , Rodrigues A.E. , Azevedo D.C.S.
Published: January 2013

Prebiotic isomaltooligosaccharides (IMOs) are composed of α-d-glucose units linked by glucosidic α (1Ø6) bonds and they remain intact until reaching the large bowels, where they are metabolized by bifidobacteria and lactobacillus. These saccharides can also be synthesized enzymatically, wherein the reaction media is composed of monosaccharides (glucose and fructose), disaccharides (sucrose and maltose), IMOs (the product of interest) and dextrans. Dextrans are readily separated by solvent precipitation; however, continuous chromatographic separation (simulated moving bed or SMB) should be an interesting option for the enrichment and purification of IMOs from mono- and disaccharides. The objective of the present work was to measure fundamental adsorption data of IMOs, mono- and disaccharides in preparative columns packed with ion-exchange resin of different cationic forms (K+, Ca+, H+ and Na+), so as to verify the influence of the cation on the selectivity and capacity. Ion exchange in H+ form showed the best performance in terms of selectivity between maltose and maltotriose, but the resin in the K+ form had superior adsorption capacities. Additionally, on the basis of equilibrium theory, optimal SMB operating conditions for resin H+ will yield the highest productivity as compared with the other cationic forms.
Effect of Ion-Exchange Modification on Hydrogen and Carbon Dioxide Adsorption Behaviour of RhoZMOF Material
Authors: Calleja Guillermo , Botas Juan A. , Martos Carmen , Orcajo Gisela , Villajos José. A.
Published: January 2013

Zeolite-like metal-organic frameworks (ZMOFs) can adsorb hydrogen and carbon dioxide because of their negatively charged structures, being able to be ion exchanged with metal cations to further increase the electrostatic field inside the framework cavities. Ion exchange of RhoZMOF with alkaline and alkaline-earth metal cations was performed up to stoichiometric levels with one single ion-exchange step. Screen effect caused by water-coordinated molecules around the exchanged cations hindered the hydrogen uptake, although slightly higher heats of hydrogen adsorption were observed for Na+, Li+, Mg2+ and Ca2+ exchanged samples. Conversely, the same exchange treatment produced a very interesting enhancement in CO2 adsorption of RhoZMOF at 303 K. Moreover, because there are no water molecules surrounding the metallic cations, RhoZMOF material was exchanged with an Li+–crown–ether complex in the nitrobenzene/acetonitrile mixture, free of water. Nitrogen and hydrogen adsorption isotherms at 77 K showed higher specific surface area and hydrogen adsorption capacity than the material with hydrated cations.
First Molecular Cytogenetic High Resolution Characterization of the NIH 3T3 Cell Line by Murine Multicolor Banding
Authors: Leibiger Christine , Kosyakova Nadezda , Mkrtchyan Hasmik , Glei Michael , Trifonov Vladimir , Liehr Thomas
Published: January 2013

Since being established in 1963, the murine fibroblast cell line NIH 3T3 has been used in thousands of studies. NIH 3T3 immortalized spontaneously and became tetraploid shortly after its establishment. Here we report the first molecular cytogenetic characterization of NIH 3T3 using fluorescence in situ hybridization based multicolor banding (mcb). Overall, a complex rearranged karyotype presenting 16 breakpoints was characterized. Also it was possible to deduce the resulting gains and losses of copy numbers in NIH 3T3. Overall, only 1.8% of the NIH 3T3 genome is disome, 26.2% tri-, 60% tetra-, 10.8% quinta-, and 1.2% hexasome. Strikingly, the cell line gained only 4 derivative chromosomes since its first cytogenetic description in 1989. An attempt to align the observed imbalances of the studied cell line with their homologous regions in humans gave the following surprising result: NIH 3T3 shows imbalances as typically seen in human solid cancers of ectodermal origin.
A Neuronal Signaling Pathway of CaMKII and Gqα Regulates Experience-Dependent Transcription oftph-1
Authors: Qin Yuqi , Zhang Xiaodong , Zhang Yun
Published: January 2013

Dynamic serotonin biosynthesis is important for serotonin function; however, the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme tryptophan hydroxylase (TPH) are poorly understood. Here, we characterize the molecular and cellular mechanisms that regulate increased transcription ofCaenorhabditis elegans tph-1in a pair of serotonergic neurons ADF during an aversive experience with pathogenic bacteria, a common environmental peril for worms. Training with pathogenic bacteria induces a learned aversion to the smell of the pathogen, a behavioral plasticity that depends on the serotonin signal from ADF neurons. We demonstrate that pathogen training increases ADF neuronal activity. While activating ADF increasestph-1transcription, inhibiting ADF activity abolishes the training effect ontph-1, demonstrating the dependence oftph-1transcriptional regulation on ADF neural activity. At the molecular level, theC. eleganshomolog of CaMKII, UNC-43, functions cell-autonomously in ADF neurons to generate training-dependent enhancement in neuronal activity andtph-1transcription, and this cell-autonomous function of UNC-43 is required for learning. Furthermore, selective expression of an activated form of UNC-43 in ADF neurons is sufficient to increase ADF activity andtph-1transcription, mimicking the training effect. Upstream of ADF, the Gqα protein EGL-30 facilitates training-dependent induction oftph-1by functional regulation of olfactory sensory neurons, which underscores the importance of sensory experience. Together, our work elucidates the molecular and cellular mechanisms whereby experience modulatestph-1transcription.
Functional Organization of Information Flow in the Corticospinal Pathway
Authors: Zinger Nofya , Harel Ran , Gabler Stephan , Israel Zvi , Prut Yifat
Published: January 2013

Transmission of information in the corticospinal (CS) route constitutes the fundamental infrastructure for voluntary actions. The anatomy of this pathway has been studied extensively, but there is little direct evidence regarding its functional organization. Here we explored the areal specificity of CS connections by studying two related questions: the functional significance of the parallel, motor, and premotor CS pathways; and the way in which finger-related motor commands are handled by this pathway. We addressed these questions by recording from primary motor (M1) and premotor cortical sites in primates (Maccaca fascicularis) performing a motor task, while measuring the evoked intraspinal unit response to single pulse cortical stimulation. Stimulation in M1 evoked spinal neuronal responses more frequently than stimulation in premotor cortex. The number of muscles excited by M1 stimulation was higher than the number excited by premotor stimulation. Within subregions of M1 finger-related sites were sparsely connected with intermediate zone interneurons and tended to affect the ventrally located motoneurons directly. These results suggest that, despite the parallel anatomical organization, the flow of motor commands is predominantly relayed via M1 to downstream elements. The functional impact of premotor cortex is weak, possibly due to inhibitory systems that can shape the flow of information in the CS pathway. Finally, the difference in spinal processing of finger versus wrist-related motor commands points to a different motor control strategy of finger versus wrist movements.
A Corticotropin Releasing Factor Pathway for Ethanol Regulation of the Ventral Tegmental Area in the Bed Nucleus of the Stria Terminalis
Authors: Silberman Yuval , Matthews Robert T. , Winder Danny G.
Published: January 2013

A growing literature suggests that catecholamines and corticotropin-releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggest that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together, these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model to determine: (1) whether catecholamines modify CRF neuron activity in the BNST; (2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons; and (3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was used to identify BNST CRF neurons for whole-cell patch-clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere-based identification strategy we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naive mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake.
Functional Specialization of Parallel Motion Detection Circuits in the Fly
Authors: Joesch Maximilian , Weber Franz , Eichner Hubert , Borst Alexander
Published: January 2013

In the flyDrosophila melanogaster, photoreceptor input to motion vision is split into two parallel pathways as represented by first-order interneurons L1 and L2 (Rister et al., 2007; Joesch et al., 2010). However, how these pathways are functionally specialized remains controversial. One study (Eichner et al., 2011) proposed that the L1-pathway evaluates only sequences of brightness increments (ON-ON), while the L2-pathway processes exclusively brightness decrements (OFF-OFF). Another study (Clark et al., 2011) proposed that each of the two pathways evaluates both ON-ON and OFF-OFF sequences. To decide between these alternatives, we recorded from motion-sensitive neurons in flies in which the output from either L1 or L2 was genetically blocked. We found that blocking L1 abolishes ON-ON responses but leaves OFF-OFF responses intact. The opposite was true, when the output from L2 was blocked. We conclude that the L1 and L2 pathways are functionally specialized to detect ON-ON and OFF-OFF sequences, respectively.
Allosteric Modulation of an Excitatory Amino Acid Transporter: The Subtype-Selective Inhibitor UCPH-101 Exerts Sustained Inhibition of EAAT1 through an Intramonomeric Site in the Trimerization Domain
Authors: Abrahamsen Bjarke , Schneider Nicole , Erichsen Mette N. , Huynh Tri H. V. , Fahlke Christoph , Bunch Lennart , Jensen Anders A.
Published: January 2013

In the present study, the mechanism of action and molecular basis for the activity of the first class of selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rodent ortholog GLAST are elucidated. The previously reported specificity of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to the EAAT4 and EAAT5 subtypes as well. Interestingly, brief exposure to UCPH-101 induces a long-lasting inactive state of EAAT1, whereas the inhibition exerted by closely related analogs is substantially more reversible in nature. In agreement with this, the kinetic properties of UCPH-101 unblocking of the transporter are considerably slower than those of UCPH-102. UCPH-101 exhibits noncompetitive inhibition of EAAT1, and its binding site in GLAST has been delineated in an elaborate mutagenesis study. Substitutions of several residues in TM3, TM4c, and TM7a of GLAST have detrimental effects on the inhibitory potency and/or efficacy of UCPH-101 while not affecting the pharmacological properties of (S)-glutamate or the competitive EAAT inhibitor TBOA significantly. Hence, UCPH-101 is proposed to target a predominantly hydrophobic crevice in the “trimerization domain” of the GLAST monomer, and the inhibitor is demonstrated to inhibit the uptake through the monomer that it binds to exclusively and not to affect substrate translocation through the other monomers in the GLAST trimer. The allosteric mode of UCPH-101 inhibition underlines the functional importance of the trimerization domain of the EAAT and demonstrates the feasibility of modulating transporter function through ligand binding to regions distant from its “transport domain.”
Convergence of Vestibular and Neck Proprioceptive Sensory Signals in the Cerebellar Interpositus
Authors: Luan Hongge , Gdowski Martha Johnson , Newlands Shawn D. , Gdowski Greg T.
Published: January 2013

The cerebellar interpositus nucleus (IN) contributes to controlling voluntary limb movements. We hypothesized that the vestibular signals within the IN might be transformed into coordinates describing the body's movement, appropriate for controlling limb movement. We tested this hypothesis by recording from IN neurons in alert squirrel monkeys during vestibular and proprioceptive stimulation produced during (1) yaw head-on-trunk rotation about the C1–C2 axis while in an orthograde posture and (2) lateral side-to-side flexion about the C6–T3 axis while in a pronograde posture. Neurons (44/67) were sensitive to vestibular stimulation (23/44 to rotation and translation, 14/44 to rotation only, 7/44 to translation only). Most neurons responded during contralateral movement. Neurons (29/44) had proprioceptive responses; the majority (21/29) were activated during neck rotation and lateral flexion. In all 29 neurons with convergent vestibular and neck proprioceptive input those inputs functionally canceled each other during all combined sensory stimulation, whether in the orthograde or pronograde posture. These results suggest that two distinct populations of IN neurons exist, each of which has vestibular sensitivity. One population carries vestibular signals that describe the head's movement in space as is traditional for vestibular signals without proprioceptive signals. A second population of neurons demonstrated precise matching of vestibular and proprioceptive signals, even for complicated stimuli, which activated the semicircular canals and otolith organs and involved both rotation and flexion in the spine. Such neurons code body (not head) motion in space, which may be the appropriate platform for controlling limb movements.
Runx1 Controls Terminal Morphology and Mechanosensitivity of VGLUT3-expressing C-Mechanoreceptors
Authors: Lou Shan , Duan Bo , Vong Linh , Lowell Bradford B. , Ma Qiufu
Published: January 2013

VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs) are proposed to mediate pleasant touch and/or pain, but the molecular programs controlling C-LTMR development are unknown. Here, we performed genetic fate mapping, showing that VGLUT3 lineage sensory neurons are divided into two groups, based on transient or persistent VGLUT3 expression. VGLUT3-transient neurons are large- or medium-diameter myelinated mechanoreceptors that form the Merkel cell-neurite complex. VGLUT3-persistent neurons are small-diameter unmyelinated neurons that are further divided into two subtypes: (1) tyrosine hydroxylase (TH)-positive C-LTMRs that form the longitudinal lanceolate endings around hairs, and (2) TH-negative neurons that form epidermal-free nerve endings. We then found that VGLUT3-persistent neurons express the runt domain transcription factor Runx1. Analyses of mice with a conditional knock-out of Runx1 in VGLUT3 lineage neurons demonstrate that Runx1 is pivotal to the development of VGLUT3-persistent neurons, such as the expression of VGLUT3 and TH and the formation of the longitudinal lanceolate endings. Furthermore, Runx1 is required to establish mechanosensitivity in C-LTMRs, by controlling the expression of the mechanically gated ion channel Piezo2. Surprisingly, both acute and chronic mechanical pain was largely unaffected in theseRunx1mutants. These findings appear to argue against the recently proposed role of VGLUT3 in C-LTMRs in mediating mechanical hypersensitivity induced by nerve injury or inflammation. Thus, our studies provide new insight into the genetic program controlling C-LTMR development and call for a revisit for the physiological functions of C-LTMRs.
Peri-Saccadic Natural Vision
Authors: Dorr Michael , Bex Peter J.
Published: January 2013

The fundamental role of the visual system is to guide behavior in natural environments. To optimize information transmission, many animals have evolved a non-homogeneous retina and serially sample visual scenes by saccadic eye movements. Such eye movements, however, introduce high-speed retinal motion and decouple external and internal reference frames. Until now, these processes have only been studied with unnatural stimuli, eye movement behavior, and tasks. These experiments confound retinotopic and geotopic coordinate systems and may probe a non-representative functional range. Here we develop a real-time, gaze-contingent display with precise spatiotemporal control over high-definition natural movies. In an active condition, human observers freely watched nature documentaries and indicated the location of periodic narrow-band contrast increments relative to their gaze position. In a passive condition under central fixation, the same retinal input was replayed to each observer by updating the video's screen position. Comparison of visual sensitivity between conditions revealed three mechanisms that the visual system has adapted to compensate for peri-saccadic vision changes. Under natural conditions we show that reduced visual sensitivity during eye movements can be explained simply by the high retinal speed during a saccade without recourse to an extra-retinal mechanism of active suppression; we give evidence for enhanced sensitivity immediately after an eye movement indicative of visual receptive fields remapping in anticipation of forthcoming spatial structure; and we demonstrate that perceptual decisions can be made in world rather than retinal coordinates.
Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications
Authors: Paz-Filho Gilberto , Mastronardi Claudio , Franco Carina Bertoldi , Wang Kevin Boyang , Wong Ma-Li , Licinio Julio
Published: January 2013

Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607
Cardiovascular risk in Japanese-Brazilian subjects
Authors: Gomes Patricia Moreira , Andrade Regina Célia Garcia de , Figueiredo Roberta Carvalho de , Pace Ana Emília , Dal Fabbro Amaury Lelis , Franco Laércio Joel , Foss Milton César , Foss-Freitas Maria Cristina
Published: January 2013

OBJECTIVE: To evaluate the prevalence of risk factors for cardiovascular disease in Japanese-Brazilian subjects. SUBJECTS AND METHODS: One hundred thirty-one residents of the Mombuca community were studied. Statistical analysis was based on the X² test, Fisher's Exact test, Student's t test, and ANOVA, at a 5% significance level. RESULTS: The average age was 56.7 years-old; 76.3% had dyslipidemia, 24.4% pre-diabetes (PDM), 10.7% type 2 diabetes mellitus (T2DM), 46.6% hypertension, 52.7% abdominal obesity, and 35.8% metabolic syndrome (MS). There were significant correlations between HOMA-IR and MS diagnosis and obesity, while HOMA-β levels were decreased in T2DM and PDM. The ankle-brachial index was positive for peripheral artery disease in 22.3% of the individuals. Electrocardiograms did not show increased evidence of myocardial ischemia. CONCLUSION: Subjects of this community are exposed to major cardiovascular risk factors, namely high prevalence of MS diagnoses and increased HOMA-IR. Arq Bras Endocrinol Metab. 2012;56(9):608-13
Densidade energética da dieta e fatores associados: como está a população de São Paulo?
Authors: Marchioni Dirce Maria Lobo , Mendes Aline , Gorgulho Bartira , Stella Roberta Horschutz , Fisberg Regina Mara
Published: January 2013

OBJETIVO: Avaliar a densidade energética da dieta de adultos do município de São Paulo e fatores associados. SUJEITOS E MÉTODOS: Participantes do estudo ISA-Capital, com amostragem probabilística (n = 710 adultos). O consumo alimentar foi avaliado pelo R24h. As correlações foram investigadas pelo coeficiente de correlação de Pearson. As associações com dados demográficos, socioeconômicos e de estilo de vida foram investigadas por modelos de regressão multivariados. RESULTADOS: A densidade energética média foi 1,98 kcal/g (IC95% [1,94; 2,01]) e correlacionou-se positivamente com a ingestão de energia, gordura, carboidrato, colesterol, gordura saturada, sacarose, gordura trans e açúcar adicionado e negativamente com fibras. Apenas idade e hábito de fumar apresentaram associação com a densidade energética. CONCLUSÕES: Os valores elevados da densidade energética da dieta e a relação demonstrada com outros constituintes nutricionais denotam má qualidade da dieta nessa população, o que pode estar contribuindo para crescentes taxas de excesso de peso. Arq Bras Endocrinol Metab. 2012;56(9):638-45
Achalasia and thyroid disease: possible autoimmune connection?
Authors: Quidute Ana Rosa P. , Freitas Eduardo Vasconcelos de , Lima Tadeu Gonçalves de , Feitosa Ana Márcia Lima , Santos Joyce Paiva dos , Correia José Walter
Published: January 2013

Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. Arq Bras Endocrinol Metab. 2012;56(9):677-82
Risk factors for nonalcoholic steatohepatitis in cryptogenic cirrhosis
Authors: Leite Andrea Benevides , Mattos Angelo Alves de , Mattos Angelo Zambam de , Coral Gabriela Perdomo , Evaldt Sandro
Published: January 2013

CONTEXT: In about 10% of patients with chronic liver disease, it is not possible to identify an etiologic factor. These cases are called cryptogenic cirrhosis. Currently, nonalcoholic steatohepatitis (NASH) is being considered as a possible etiologic factor for a significant segment of patients that presents with cryptogenic cirrhosis. OBJECTIVE: To estimate the prevalence of risk factors for NASH in patients with cryptogenic cirrhosis, in order to verify if there is a causal relationship between them. METHOD: Cross-sectional study, with evaluation of the demographic and laboratorial data of patients with cryptogenic cirrhosis. They were compared with data obtained from a group with NASH and a group with alcoholic and/or hepatitis C (HCV) cirrhosis. RESULTS: Forty seven patients with cryptogenic cirrhosis were evaluated, 47 with NASH and 196 with HCV and/or alcoholic cirrhosis. The mean age of patients with cryptogenic cirrhosis was 52 years, while in those with NASH it was 46.4 years (P = 0,041). The group with cryptogenic cirrhosis had 23 female and 24 male patients. Of the patients who presented with NASH, 68.1% were female. Of the patients who presented with alcoholic/HCV cirrhosis, 64.8% were male. There were no statistically significant differences between the groups. In cryptogenic cirrhosis patients, the following prevalences could be observed: impaired fasting glycemia - 68.2%; obesity - 27.5%; total hypercholesterolemia - 27.9%; low HDL levels - 58.1% (women - 81%; men - 36.4%); hypertriglyceridemia - 16.3%. The results seen in cryptogenic cirrhosis patients showed statistical similarity with the results of the NASH group regarding fasting glycemia (62.8%) and male HDL levels (53.8%). The comparison with the alcoholic/HCV cirrhosis group showed statistical differences regarding fasting glycemia (45.2%), hypercholesterolemia (13.3%) and female HDL levels (50.8%). CONCLUSIONS: It is not possible to establish a causal relationship between cryptogenic cirrhosis and NASH. Only data related to fasting glycemia and HDL levels in male patients showed statistical similarities between both groups of patients.
Peristomal infection after percutaneous endoscopic gastrostomy: a 7-year surveillance of 297 patients
Authors: Duarte Helena , Santos Carla , Capelas Manuel Luís , Fonseca Jorge
Published: January 2013

CONTEXT: Healthcare-associated infection represents the most frequent adverse event during care delivery. Medical advances like percutaneous endoscopic gastrostomy have brought improvement on quality of life to patients but an increased risk of healthcare-associated infection. Predictive risk factors for peristomal wound infection are largely unknown but evidence suggests that antibiotic prophylaxis and preventive strategies related to infection control may reduce infection rates. OBJECTIVES: The primary aim was to evaluate the global prevalence rate of peristomal infection. Secondary objectives were to characterise the positive culture results, to evaluate the prophylactic antibiotic protocol and to identify potential risk factors for peristomal infection. METHODS: Retrospective study of 297 patients with percutaneous endoscopic gastrostomy performed at a general hospital between January 2004 and September 2010. Patients received prophylactic cefazolin before the endoscopic gastrostomy procedure. Medical records were reviewed for demographic data, underling disease conditions to percutaneous endoscopic gastrostomy and patient potential intrinsic risk factors. Statistical analysis was made with the statistical program SPSS 17.0. RESULTS: A total of 297 percutaneous endoscopic gastrostomy tubes were inserted. Wound infection occurred in 36 patients (12.1%). Staphylococcus aureus methicillin resistant was the most frequently isolated microorganism (33.3%) followed by Pseudomonas aeruginosa (30.6%). The incidence rate had been rising each year and differ from 4.65% in 2004/2007 to 17.9% in 2008/2010. This finding was consistent with the increasing of prevalence global infection rates of the hospital. Most of the infections (55.6%) were detected in the first 10 days post procedure. There was no significant difference in age, body mass index values, mean survival time and duration of percutaneous endoscopic gastrostomy feeding between patients with and without periostomal infection. Institutional factors, namely global prevalence infection rates and the endemic character of Staphylococcus aureus methicillin resistant, play an important role in peristomal infection rates. Traditional antibiotic prophylaxis with cefazolin is not adequate due to the prevalence of resistant organisms. CONCLUSIONS: Peristomal infection is a frequent problem with clinical impact in percutaneous endoscopic gastrostomy patients and should be considered a healthcare associated infection. The antimicrobial prophylaxis regimens using cephalosporins are not adequate and need to be reviewed due to the high prevalence of Staphylococcus aureus methicillin resistant and other resistant organisms in hospitals and nursing homes.
Acute diarrhea in hospitalized children of the municipality of juiz de fora, MG, Brazil: prevalence and risk factors associated with disease severity
Authors: Rocha Monica Couto Guedes Sejanes da , Carminate Delaine La Gatta , Tibiriçá Sandra Helena Cerrato , Carvalho Iná Pires de , Silva Maria Luzia da Rosa e , Chebli Júlio Maria Fonseca
Published: January 2013

CONTEXT: Acute diarrhea is a common cause of hospitalization among children under 5 years of age. Knowing the prevalence and risk factors associated with the severity of acute diarrhea is essential to control morbidity and mortality. OBJECTIVE: Describe the prevalence of demographic, epidemiologic and clinical features of children under 6 years of age hospitalized for acute diarrhea, and investigate the association between these determinants and the severity of the diarrheic episode. METHOD: Retrospective, cross-sectional study, during the period from January, 2005 through December, 2008, in the municipality of Juiz de Fora, MG, Brazil. Files from 6,201 children from 0 to 6 years of age, hospitalized in two public teaching institutions (which account for 84% of all the hospitalizations in the municipality), were assessed. Acute diarrhea was defined as the presence of at least three evacuations of liquid or loose stools, within 24 hours, for a maximum period of 14 days. The patients with acute diarrhea were divided in two groups, according to disease severity, severe diarrhea being considered whenever hospitalization lasted for at least 4 days. Epidemiologic and clinical data were assessed and compared through the application of the chi-squared test and the binomial logistic regression model. RESULTS: The prevalence rate for admission due to acute diarrhea was 8.4%. The factors significantly associated with the severity of the diarrheic episode were: age under 6 months (P = 0.01, OR = 2.762); disease onset during fall (P = 0.033, OR = 1.742), presence of fever (P = 0.017, OR = 1.715) and antibiotic use during hospitalization (P = 0.000, OR = 3.872). CONCLUSIONS: Diarrhea is the third most common cause of hospitalization among children under 6 years of age in Juiz de Fora. Young age (under or equal to 6 months), fever, antibiotic use during hospitalization and disease onset during fall are risk factors associated with longer hospital stay.
Prognostic factors for survival in patients with colorectal liver metastases: experience of a single brazilian cancer center
Authors: Ribeiro Héber Salvador de Castro , Stevanato-Filho Paulo Roberto , Costa Jr. Wilson Luiz da , Diniz Alessandro Landskron , Herman Paulo , Coimbra Felipe José Fernández
Published: January 2013

CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients showed similar results to those pointed in international series. The occurrence of major postoperative complications appears to be able to compromise overall survival and further investigation in needed in this topic.
Diversity and habitat preferences of Carabidae and Staphylinidae (Coleoptera) in two agroecosystems
Authors: Martins Ivan Carlos Fernandes , Cividanes Francisco Jorge , Ide Sergio , Haddad Gianni Queiroz
Published: January 2013

The present study had as objective determine the diversity and abundance of adults Carabidae and Staphylinidae in two areas, constituted by forest fragment and soybean/corn crops under conventional tillage and no-tillage systems and to analyze the distribution and preference of those beetles for the habitat. The beetles were sampled with 48 pitfall traps. In both experimental areas, two parallel transects of pitfall traps were installed. Each transect had 100 m in the crop and 100 m in the forest fragment. Four traps were close to each other (1 m) in the edge between the crop and the forest fragment, the other traps were installed each 10 m. The obtained data were submitted to the faunistic analysis and the preference of the species by habitat was obtained by cluster analysis. The results demonstrated that the type of crop system (conventional tillage or no-tillage) might have influenced the diversity of species of Carabidae and Staphylinidae. The cluster analysis evidenced that the carabids may prefer a specific habitat. In the present study, the distribution of carabids and staphylinids in the three habitats showed that these beetles have potential to be dispersed at great distances inside the crop.