bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure meets function: actin filaments and myosin motors in the axon
Authors: Arnold Don B. , Gallo Gianluca 
Published: October 2013

AbstractThis review focuses on recent advances in the understanding of the organization and roles of actin filaments, and associated myosin motor proteins, in regulating the structure and function of the axon shaft. ‘Patches’ of actin filaments have emerged as a major type of actin filament organization in axons. In the distal axon, patches function as precursors to the formation of filopodia and branches. At the axon initial segment, patches locally capture membranous organelles and contribute to polarized trafficking. The trapping function of patches at the initial segment can be ascribed to interactions with myosin motors, and likely also applies to patches in the more distal axon. Finally, submembranous rings of actin filaments were recently described in axons, which form an actin‐spectrin cytoskeleton, likely contributing to the maintenance of axon integrity. Continued investigation into the roles of axonal actin filaments and myosins will shed light on fundamental aspects of the development, adult function and the repair of axons in the nervous system.imageThis review focuses on recent advances in the understanding of the organization and roles of actin filaments, and associated myosin motor proteins, in regulating the structure and function of the axon shaft. Actin filament patches at the initial segment capture vesicles incorrectly being transported anterogradely into the axon (see schematic). When the vesicle is released from the patch, it undergoes retrograde transport back to the soma. Along the distal axon, actin patches serve as precursors to the emergence of filopodia, the first step in axon branching.
Magnetic resonance fetal right lung volumetry and its efficacy in predicting postnatal short‐term outcomes of congenital left‐sided diaphragmatic hernia
Authors: Hidaka Nobuhiro , Ishii Keisuke , Furutake Yoko , Yamamoto Ryo , Sasahara Jun , Mitsuda Nobuaki 
Published: October 2013

AbstractAimWe aimed to investigate whether the ratio of magnetic resonance imaging (MRI)‐measured right lung volume (RLV) to ultrasonography‐estimated bodyweight (RLV/BW) and observed‐to‐expected (o/e) RLV are of diagnostic value in predicting postnatal outcomes of left congenital diaphragmatic hernia (CDH).Material and MethodsWe included 32 CDH patients and 34 control subjects. Manually outlined fetal right lung areas on MRI were multiplied by the slice thickness and added to determine the entire volume. The association between RLV and RLV/BW with gestational age in the controls was examined using regression analysis. RLV/BW and o/e RLV were compared between surviving and non‐surviving neonates with CDH.ResultsThe expected fetal RLV was derived using the formula RLV (mm3) = 1.717 × (gestational weeks)2.82. In the controls, RLV/BW was nearly constant during the third trimester. The 27 survivors with CDH had a median RLV/BW of 10.7 and a median o/e RLV of 60.0, whereas the five non‐surviving neonates had a median RLV/BW of 4.3 and a median o/e RLV of 22.6; the differences were statistically significant.ConclusionAssessment of fetal lungs by MRI volumetry is reliable for clinical use. RLV/BW and o/e RLV are potential predictors of postnatal outcomes of left CDH.
Paraneoplastic cerebellar degeneration caused by ovarian clear‐cell carcinoma
Authors: Negishi Y. , Sakai K. , Noguchi Y. , Iwasaki N. , Kawai N. 
Published: October 2013

AbstractParaneoplastic cerebellar degeneration is a paraneoplastic neurological syndrome caused by the remote effect of certain systemic cancers and is characterized by subacute cerebellar symptoms. A 62‐year‐old woman suffering from unidentified cerebellar symptoms was admitted to our hospital. Paraneoplastic cerebellar degeneration was suspected and ovarian cancer was detected after the systemic examination for malignancy. The symptoms of vertigo and dysarthria were improved a little after surgical operation and treatments of γ‐globulin, steroid pulse and tacrolimus hydrate. The cerebellar symptoms of paraneoplastic cerebellar degeneration are often evident prior to detection of malignancy. It is important to perform systemic examination for malignancy in case of unidentified cerebellar symptoms.
Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model ofDown syndrome
Authors: Corrales Andrea , Vidal Rebeca , García Susana , Vidal Verónica , Martínez Paula , García Eva , Flórez Jesús , Sanchez‐Barceló Emilio J. , Martínez‐Cué Carmen , Rueda Noemí 
Published: October 2013

AbstractThe Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of theirCNSdue to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age‐related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration inTSmice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed inTSmice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition inTSmice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampalLTPin trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus ofTSmice. These results indicate that the cognitive‐enhancing effects of melatonin in adultTSmice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression ofDSneuropathology.
Comparative assessment of genetic diversity between wild and cultivated barley using gSSR and EST‐SSR markers
Authors: Nandha Prabhjot S. , Singh Jaswinder 
Published: October 2013

AbstractBarley is an economically important cereal crop especially for feed and malt production, but its value as food is increasing due to various health benefits. Wild barley is the progenitor of modern day barley cultivars possessing a rich source of genetic variation for various biotic and abiotic stresses. Species‐specific molecular markers have great potential for efficient introgression of these important traits from wild to cultivated barley. In the present study, 140 microsatellite markers were screened to assess the genetic variation and species‐specific markers between wild and cultivated germplasm. Of these 140, a polymorphic set of 48 genomic (gSSR) and 16 EST‐SSRs amplified a total of 685 alleles. Cluster analysis discriminated all 47 accessions and classified wild and cultivated genotypes into two distinct groups, according to their geographic origin. Our analysis indicated that gSSRs were more informative than EST‐based SSRs. Results from PCoA analysis for species‐specific alleles clearly suggest that wild barley genotypes contain a higher number of unique alleles.
Garbage‐can Policy‐making Meets Neo‐liberal Ideology: Twenty Five Years of Redundant Reform of theEnglishNationalHealthService
Authors: Paton Calum 
Published: October 2013

AbstractThe garbage‐can theory of decision‐making (Cohenet al. 1972), has been adapted into a perspective on policy‐making, with adaptations of the approach placing notable emphasis upon the health sector (Kingdon 2006;Paton 2006). This article creates an adapted ‘garbage‐can’ framework to help explain each stage of the reform of theEnglishNationalHealthService (NHS) over the last 25 years.The emergence of the key idea and resultant policy at each stage of reform of theEnglishNHShas been arational and indeed sometimes irrational. Policy has reflected advocacy by policy‐salesmen (Kingdon 2002), proffering ‘solutions’ to ill‐defined problems and answers to unasked questions, and politicians' short‐termist responses at each decision‐point.Yet the garbage‐can alone is not enough: if arationality rules in policy‐making day to day, this does not mean that there is not an overall ideological context, trend or bias in reform. The article also posits that ‘market reform’ has derived from the ideological hegemony of a naive anti‐statism (hostility to a misleadingly defined and often mythological ‘centralist state’) in public services and enthusiasm for market competition rather than any evidence‐based application of pro‐market ideas to health policy.A question arises: how are these two approaches (short‐term arationality and longer‐term ideological bias) combined in explanation of how policy over time is biased in a particular direction while seemingly arbitrary and directionless at each messy decision‐point. The article attempts to combine the insights of a garbage‐can approach with wider explanations of ideological hegemony.
Direct isolation of flavonoids from plants using ultra‐small anatase TiO2 nanoparticles
Authors: Kurepa Jasmina , Nakabayashi Ryo , Paunesku Tatjana , Suzuki Makoto , Saito Kazuki , Woloschak Gayle E. , Smalle Jan A. 
Published: October 2013

SummarySurface functionalization of nanoparticles has become an important tool for in vivo delivery of bioactive agents to their target sites. Here we describe the reverse strategy, nanoharvesting, in which nanoparticles are used as a tool to isolate bioactive compounds from living cells. Anatase TiO2 nanoparticles smaller than 20 nm form strong bonds with molecules bearing enediol and especially catechol groups. We show that these nanoparticles enter plant cells, conjugate enediol and catechol group‐rich flavonoids in situ, and exit plant cells as flavonoid‐nanoparticle conjugates. The source plant tissues remain viable after treatment. As predicted by the surface chemistry of anatase TiO2 nanoparticles, quercetin‐based flavonoids were enriched amongst the nanoharvested flavonoid species. Nanoharvesting eliminates the use of organic solvents, allows spectral identification of the isolated compounds, and opens new avenues for use of nanomaterials for coupled isolation and testing of bioactive properties of plant‐synthesized compounds.
Spatio‐temporal analysis of cellulose synthesis during cell plate formation in Arabidopsis
Authors: Miart Fabien , Desprez Thierry , Biot Eric , Morin Halima , Belcram Katia , Höfte Herman , Gonneau Martine , Vernhettes Samantha 
Published: October 2013

SummaryDuring cytokinesis a new crosswall is rapidly laid down. This process involves the formation at the cell equator of a tubulo‐vesicular membrane network (TVN). This TVN evolves into a tubular network (TN) and a planar fenestrated sheet, which extends at its periphery before fusing to the mother cell wall. The role of cell wall polymers in cell plate assembly is poorly understood. We used specific stains and GFP‐labelled cellulose synthases (CESAs) to show that cellulose, as well as three distinct CESAs, accumulated in the cell plate already at the TVN stage. This early presence suggests that cellulose is extruded into the tubular membrane structures of the TVN. Co‐localisation studies using GFP–CESAs suggest the delivery of cellulose synthase complexes (CSCs) to the cell plate via phragmoplast‐associated vesicles. In the more mature TN part of the cell plate, we observed delivery of GFP–CESA from doughnut‐shaped organelles, presumably Golgi bodies. During the conversion of the TN into a planar fenestrated sheet, the GFP–CESA density diminished, whereas GFP–CESA levels remained high in the TVN zone at the periphery of the expanding cell plate. We observed retrieval of GFP–CESA in clathrin‐containing structures from the central zone of the cell plate and from the plasma membrane of the mother cell, which may contribute to the recycling of CESAs to the peripheral growth zone of the cell plate. These observations, together with mutant phenotypes of cellulose‐deficient mutants and pharmacological experiments, suggest a key role for cellulose synthesis already at early stages of cell plate assembly.
A BrachyPhantom for verification of dose calculation of HDR brachytherapy planning system
Authors: Austerlitz C. , Campos C. A. T. 
Published: October 2013

Purpose:To develop a calibration phantom for192Ir high dose rate (HDR) brachytherapy units that renders possible the direct measurement of absorbed dose to water and verification of treatment planning system.Methods:A phantom, herein designated BrachyPhantom, consists of a Solid Water™ 8‐cm high cylinder with a diameter of 14 cm cavity in its axis that allows the positioning of an A1SL ionization chamber with its reference measuring point at the midheight of the cylinderˈs axis. Inside the BrachyPhantom, at a 3‐cm radial distance from the chamberˈs reference measuring point, there is a circular channel connected to a cylindrical‐guide cavity that allows the insertion of a 6‐French flexible plastic catheter from the BrachyPhantom surface. The PENELOPE Monte Carlo code was used to calculate a factor,, to correct the reading of the ionization chamber to a full scatter condition in liquid water. The verification of dose calculation of a HDR brachytherapy treatment planning system was performed by inserting a catheter with a dummy source in the phantom channel and scanning it with a CT. The CT scan was then transferred to the HDR computer program in which a multiple treatment plan was programmed to deliver a total dose of 150 cGy to the ionization chamber. The instrument reading was then converted to absorbed dose to water using the Ngas formalism and the factor. Likewise, the absorbed dose to water was calculated using the source strength, Sk, values provided by 15 institutions visited in this work.Results:A value of 1.020 (0.09%,k = 2) was found for . The expanded uncertainty in the absorbed dose assessed with the BrachyPhantom was found to be 2.12% (k = 1). To an associated Sk of 27.8 cGy m2 h−1, the total irradiation time to deliver 150 cGy to the ionization chamber point of reference was 161.0 s. The deviation between the absorbed doses to water assessed with the BrachyPhantom and those calculated by the treatment plans and using the Sk values did not exceed ±3% and ±1.6%, respectively.Conclusions:The BrachyPhantom may be conveniently used for quality assurance and/or verification of HDR planning system witha priori threshold level to spot problems of 2% and ±3%, respectively, and in the long run save time for the medical physicist.
Therapeutic Efficacy of SQ641-NE against Mycobacterium tuberculosis
Authors: Nikonenko Boris , Reddy Venkata M. , Bogatcheva Elena , Protopopova Marina , Einck Leo , Nacy Carol A. 
Published: October 2013

ABSTRACT

A phospholipid-based nanoemulsion formulation of SQ641 (SQ641-NE) was active against intracellular
Mycobacterium tuberculosis
in J774A.1 mouse macrophages, although SQ641 by itself was not. Intravenous (i.v.) SQ641-NE was cleared from circulation and reached peak concentrations in lung and spleen in 1 h. In a murine tuberculosis (TB) model, 8 i.v. doses of SQ641-NE at 100 mg/kg of body weight over 4 weeks caused a 1.73 log
10
CFU reduction of
M. tuberculosis
in spleen and were generally bacteriostatic in lungs.
A Novel Dengue Virus Inhibitor, BP13944, Discovered by High-Throughput Screening with Dengue Virus Replicon Cells Selects for Resistance in the Viral NS2B/NS3 Protease
Authors: Yang Chi-Chen , Hu Han-Shu , Wu Ren-Huang , Wu Szu-Huei , Lee Shiow-Ju , Jiaang Weir-Torn , Chern Jyh-Haur , Huang Zhi-Shun , Wu Huey-Nan , Chang Chung-Ming , Yueh Andrew 
Published: October 2013

ABSTRACT

Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using a stable cell line harboring an efficient luciferase replicon of DENV serotype 2 (DENV-2). BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC
50
) of 1.03 ± 0.09 μM. Without detectable cytotoxicity, the compound inhibited replication or viral RNA synthesis in all four serotypes of DENV but not in Japanese encephalitis virus (JEV). Sequencing analyses of several individual clones derived from BP13944-resistant RNAs purified from cells harboring the DENV-2 replicon revealed a consensus amino acid substitution (E66G) in the region of the NS3 protease domain. Introduction of E66G into the DENV replicon, an infectious DENV cDNA clone, and recombinant NS2B/NS3 protease constructs conferred 15.2-, 17.2-, and 3.1-fold resistance to BP13944, respectively. Our results identify an effective small-molecule inhibitor, BP13944, which likely targets the DENV NS3 protease. BP13944 could be considered part of a more effective treatment regime for inhibiting DENV in the future.
Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum Antiviral Lectin Griffithsin in Two Laboratory Rodent Models
Authors: Barton Christopher , Kouokam J. Calvin , Lasnik Amanda B. , Foreman Oded , Cambon Alexander , Brock Guy , Montefiori David C. , Vojdani Fakhrieh , McCormick Alison A. , O'Keefe Barry R. , Palmer Kenneth E. 
Published: October 2013

ABSTRACT
Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.
Amidate Prodrugs of 9-[2-(Phosphonomethoxy)Ethyl]Adenine as Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis
Authors: Šmídková Markéta , Dvořáková Alexandra , Tloušt'ová Eva , Česnek Michal , Janeba Zlatko , Mertlíková-Kaiserová Helena 
Published: October 2013

ABSTRACT

Adenylate cyclase toxin (ACT) is the key virulence factor of
Bordetella pertussis
that facilitates its invasion into the mammalian body. 9-[2-(Phosphonomethoxy)ethyl]adenine diphosphate (PMEApp), the active metabolite of the antiviral drug bis(POM)PMEA (adefovir dipivoxil), has been shown to inhibit ACT. The objective of this study was to evaluate six novel amidate prodrugs of PMEA, both phenyloxy phosphonamidates and phosphonodiamidates, for their ability to inhibit ACT activity in the J774A.1 macrophage cell line. The two phenyloxy phosphonamidate prodrugs exhibited greater inhibitory activity (50% inhibitory concentration [IC
50
] = 22 and 46 nM) than the phosphonodiamidates (IC
50
= 84 to 3,960 nM). The inhibitory activity of the prodrugs correlated with their lipophilicity and the degree of their hydrolysis into free PMEA in J774A.1 cells. Although the prodrugs did not inhibit ACT as effectively as bis(POM)PMEA (IC
50
= 6 nM), they were significantly less cytotoxic. Moreover, they all reduced apoptotic effects of ACT and prevented an ACT-induced elevation of intracellular [Ca
2+
]i. The amidate prodrugs were less susceptible to degradation in Caco-2 cells compared to bis(POM)PMEA, while they exerted good transepithelial permeability in this assay. As a consequence, a large amount of intact amidate prodrug is expected to be available to target macrophages
in vivo
. This feature makes nontoxic amidate prodrugs attractive candidates for further investigation as novel antimicrobial agents.
The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumoniae
Authors: Ferrándiz María-José , de la Campa Adela G. 
Published: October 2013

ABSTRACT

We studied the transcriptomic response of
Streptococcus pneumoniae
to levofloxacin (LVX) under conditions inhibiting topoisomerase IV but not gyrase. Although a complex transcriptomic response was observed, the most outstanding result was the upregulation of the genes of the
fatDCEB
operon, involved in iron (Fe
2+
and Fe
3+
) uptake, which were the only genes varying under every condition tested. Although the inhibition of topoisomerase IV by levofloxacin did not have a detectable effect in the level of global supercoiling, increases in general supercoiling and
fatD
transcription were observed after topoisomerase I inhibition, while the opposite was observed after gyrase inhibition with novobiocin. Since
fatDCEB
is located in a topological chromosomal domain downregulated by DNA relaxation, we studied the transcription of a copy of the 422-bp (including the P

fat

promoter) region located upstream of
fatDCEB
fused to the
cat
reporter inserted into the chromosome 106 kb away from its native position: P

fat

fatD
was upregulated in the presence of LVX in its native location, whereas no change was observed in the P

fat

cat
construction. Results suggest that topological changes are indeed involved in P

fat

fatDCE
transcription. Upregulation of
fatDCEB
would lead to an increase of intracellular iron and, in turn, to the activation of the Fenton reaction and the increase of reactive oxygen species. In accordance, we observed an attenuation of levofloxacin lethality in iron-deficient media and in a strain lacking the gene coding for SpxB, the main source of hydrogen peroxide. In addition, we observed an increase of reactive oxygen species that contributed to levofloxacin lethality.