bluuebunny/crossref_metadata_2025 huggingface dataset:
A dramatic, objective antiandrogen withdrawal response: case report and review of the literature
Authors: Lau Yiu-Keung , Chadha Manpreet K , Litwin Alan , Trump Donald L
Published: November 2008

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.
Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer
Authors: Zhang Shiwu , Qi Lisha , Li Man , Zhang Danfang , Xu Shaoyan , Wang Ning , Sun Baocun
Published: November 2008

Objective

To identify the roles of CXCL12 and CXCR4 and the associated mechanism involved in perineural invasion of prostate cancer.

Methods

The distribution and expression of CXCL12, CXCR4, MMP-2 and MMP-9 in human prostate cancer and in tumor cells invading nerve tissue were studied with immunohistochemical staining. The effects of exogenous CXCL12 and CXCR4 antagonist AMD3100 on PC3 prostate cancer cells invasiveness were assessed in vitro and in vivo.

Results

The expression of CXCL12, CXCR4, MMP-2, and MMP-9 in human prostate cancer were higher than those in hyperplastic prostate tissues (P< 0.05). In vitro CXCL12 could stimulate the PC3 cells invasiveness (P< 0.05) while AMD3100 could inhibit invasiveness. In vivo, the number of nerves around the tumor tissue in the group treated with CXCL12 was significantly higher than that found in the control group (P< 0.05). Both the control group and the CXCL12-treated group had more nerves number near the tumor tissue than it found in the AMD3100-treated group. The positive cell number of CXCL12, CXCR4, MMP-2, MMP-9, and NGF expression ranked from highest to lowest, were the CXCL12-treated, the control, and the AMD3100-treated group(P< 0.05).

Conclusion

CXCL12 and its receptor CXCR4 along with MMP-2 and MMP-9 are related with prostate cancer perineural invasion.
Antitumor efficacy of combination of interferon-gamma-inducible protein 10 gene with gemcitabine, a study in murine model
Authors: Mei Kai , Wang Lian , Tian Ling , Yu Jingrui , Zhang Zhixuan , Wei Yuquan
Published: November 2008

Background

Interferon-γ-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects.

Methods

To elucidate the mechanisms of IP-10 gene combined with a chemotherapy agent, we intramuscularly injected pBLAST-IP-10 expression plasmid combined with gemcitabine into tumor-bearing mice.

Results

The proliferation of endothelial cells was effectively inhibited by IP-10 combined with gemcitabinein vitro. Treatment with pBLAST-IP-10 twice a week for 4 weeks combined with gemcitabine 10 mg/kg (once a week) resulted in sustained high level of IP-10 protein in serum, inhibition of tumor growth and prolongation of the survival of tumor-bearing mice. Compared with administration of IP-10 plasmid or gemcitabine alone, the angiogenesis in tumors were apparently inhibited, and the numbers of apoptotic cells and lymphocytes in tumor increased in the combination therapy group.

Conclusion

Our data indicate that the gene therapy of antiangiogenesis by intramuscular delivery of plasmid DNA encoding IP-10 combined with gemcitabine has synergistic effects on tomor by inhibiting the proliferation of endothelail cells, inducing the apoptosis of tumor cells, and recruiting lymphocytes to tumor in murine models. The present findings provided evidence of antitumor effects of genetherapy combined with chemotherapy.
Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study
Authors: Engvall Inga-Lill , Svensson Björn , Tengstrand Birgitta , Brismar Kerstin , Hafström Ingiäld ,   the BARFOT study group
Published: November 2008

Introduction

Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density.

Methods

One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months.

Results

Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group.

Conclusions

Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.
A simple, fast, and accurate method of phylogenomic inference
Authors: Wu Martin , Eisen Jonathan A
Published: November 2008

The explosive growth of genomic data provides an opportunity to make increased use of protein markers for phylogenetic inference. We have developed an automated pipeline for phylogenomic analysis (AMPHORA) that overcomes the existing bottlenecks limiting large-scale protein phylogenetic inference. We demonstrated its high throughput capabilities and high quality results by constructing a genome tree of 578 bacterial species and by assigning phylotypes to 18,607 protein markers identified in metagenomic data collected from the Sargasso Sea.
Robust processing of magnetotelluric data in the AMT dead band using the continuous wavelet transform
Authors: Garcia Xavier , Jones Alan G.
Published: November 2008

The energy sources for magnetotellurics (MT) at frequencies above [Formula: see text] are electromagnetic waves generated by distant lightning storms propagating globally within the earth-ionosphere waveguide. The nature of the sources and properties of this waveguide display diurnal and seasonal variations that can cause significant signal amplitude attenuation, especially at [Formula: see text] frequencies — the so-called audiomagnetotelluric (AMT) dead band. This lack of energy results in unreliable MT response estimates; and, given that in crystalline environments ore bodies located at some [Formula: see text] depth are sensed initially by AMT data within the dead band, this leads to poor inherent geometric resolution of target structures. We propose a new time-series processing technique that uses localization properties of the wavelet transform to select the most energetic events. Subsequently, two coherence thresholds and a series of robust weights are implemented to obtain the most reliable MT response estimates. Finally, errors are estimated using a nonparametric jackknife algorithm. We applied this algorithm to AMT data collected in northern Canada. These data were processed previously using traditional robust algorithms and using a telluric-telluric magnetotelluric (TTMT) technique. The results show a significant improvement in estimates for the AMT dead band and permit their quantitative interpretation.
Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease
Authors: Baker A. R. , Harte A. L. , Howell N. , Pritlove D. C. , Ranasinghe A. M. , da Silva N. F. , Youssef E. M. , Khunti K. , Davies M. J. , Bonser R. S. , Kumar S. , Pagano D. , McTernan P. G.
Published: November 2008

Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated.

Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-κB (NFκB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects.

Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies.

Results: Western blotting showed epicardial AT had significantly higher NFκB, inhibitory-κB kinase (IKK)-γ, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-α. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P<0.05].

Conclusion: Epicardial AT from patients with CAD shows increased NFκB, IKKβ, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFκB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.
Central Control of Body Weight and Appetite
Authors: Woods Stephen C. , D'Alessio David A.
Published: November 2008

Context

Energy balance is critical for survival and health, and control of food intake is an integral part of this process. This report reviews hormonal signals that influence food intake and their clinical applications.

Evidence Acquisition

A relatively novel insight is that satiation signals that control meal size and adiposity signals that signify the amount of body fat are distinct and interact in the hypothalamus and elsewhere to control energy homeostasis. This review focuses upon recent literature addressing the integration of satiation and adiposity signals and therapeutic implications for treatment of obesity.

Evidence Synthesis

During meals, signals such as cholecystokinin arise primarily from the GI tract to cause satiation and meal termination; signals secreted in proportion to body fat such as insulin and leptin interact with satiation signals and provide effective regulation by dictating meal size to amounts that are appropriate for body fatness, or stored energy. Although satiation and adiposity signals are myriad and redundant and reduce food intake, there are few known orexigenic signals; thus, initiation of meals is not subject to the degree of homeostatic regulation that cessation of eating is. There are now drugs available that act through receptors for satiation factors and which cause weight loss, demonstrating that this system is amenable to manipulation for therapeutic goals.

Conclusions

Although progress on effective medical therapies for obesity has been relatively slow in coming, advances in understanding the central regulation of food intake may ultimately be turned into useful treatment options.
Growth-speed-correlated localization of exocyst and polarisome components in growth zones of Ashbya gossypii hyphal tips
Authors: Köhli Michael , Galati Virginie , Boudier Kamila , Roberson Robert W. , Philippsen Peter
Published: November 2008

We use the fungus Ashbya gossypii to investigate how its polar growth machinery is organized to achieve sustained hyphal growth. In slowly elongating hyphae exocyst, cell polarity and polarisome proteins permanently localize as cortical cap at hyphal tips, thus defining the zone of secretory vesicle fusion. In tenfold faster growing hyphae, this zone is only slightly enlarged demonstrating a capacity of hyphal growth zones to increase rates of vesicle processing to reach higher speeds. Concomitant with this increase, vesicles accumulate as spheroid associated with the tip cortex, indicating that a Spitzenkörper forms in fast hyphae. We also found spheroid-like accumulations for the exocyst components AgSec3, AgSec5, AgExo70 and the polarisome components AgSpa2, AgBni1 and AgPea2 (but not AgBud6 or cell polarity factors such as AgCdc42 or AgBem1). The localization of AgSpa2, AgPea2 and AgBni1 depend on each other but only marginally on AgBud6, as concluded from a set of deletions. Our data define three conditions to achieve fast growth at hyphal tips: permanent presence of the polarity machinery in a confined cortical area, organized accumulation of vesicles and a subset of polarity components close to this area, and spatial separation of the zones of exocytosis (tip front) and endocytosis (tip rim).
Thiiranation of 2′-Adamantylidene-9-benzonorbornenylidene and cis- and trans-Cyclooctenes with 4,4′-Dithiodimorpholine in Acetic Anhydride
Authors: Sugihara Yoshiaki , Koyama Hiroki , Yasukawa Yuri , Nakayama Juzo
Published: November 2008

Thiiranation of 2′-adamantylidene-9-benzonorbornenylidene (1) with 4,4′-dithiodimorpholine (5) in Ac2O at −15 °C gave thiiranes 2 and 3 without the decomposition of the thermodynamically less stable 3. cis- and trans-Cyclooctenes underwent thiiranation with retention of their stereochemistry.
Direct Preparation of Primary Amides by Reaction of Carboxylic Acids and Ammonia in Alcohols Using DMT-MM
Authors: Mizuhara Tsukasa , Hioki Kazuhito , Yamada Megumi , Sasaki Hideaki , Morisaki Daiki , Kunishima Munetaka
Published: November 2008

A simple and mild method for the direct conversion of carboxylic acids to primary amides has been developed by using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). The reaction proceeds by adding DMT-MM to a mixture of carboxylic acids and an ammonia source in methanol, 2-propanol, or THF without any additives. The present method is quite practical in that aqueous ammonia or ammonium chloride/triethylamine can be used as an ammonia source. Methanol or 2-propanol is an ideal polar solvent because it is inexpensive, can be removed by rotary evaporator, and solubilizes many kinds of polar or nonpolar compounds.
Pickering Emulsions and Microcapsules Stabilized by Solid Particles and Biological Lipids
Authors: Nonomura Yoshimune , Suzuki Mustumi
Published: November 2008

We succeeded in preparing emulsions and microcapsules stabilized by solid particles and biological lipids. The biological lipids prevent the collapse of the microcapsules.
Fluoride-ion-mediated Hydrolysis of Phosphoric Acid Esters, Amides, and Phosphorous Acid Esters Leading to Phosphorofluoridic, Phosphoramide Fluoridic, and Phosphonic Acid Monoester Salts
Authors: Murai Toshiaki , Takenaka Tohru , Inaji Shinsuke , Tonomura Yusuke
Published: November 2008

Fluoride-ion-promoted hydrolysis of phosphoric acid esters and amides to give phosphorofluoridic and phosphoramide fluoridic acid monoester salts takes place upon treatment with a THF solution of TBAF, whereas a similar treatment of phosphorous acid esters generates phosphonic acid monoester salts selectively without introduction of fluorine.
Dynamic Behavior of a Fluorescent Probe, a Swallow-tailed Perylene Derivative for Detecting Hydroperoxides
Authors: Ito Fuyuki , Ariyoshi Tomoyuki , Soh Nobuaki , Kakiuchi Toshifumi , Inoue Tatsuaki , Imato Toshihiko , Nagamura Toshihiko
Published: November 2008

Dynamic behavior of a fluorescent probe, a swallow-tailed perylene derivative (Spy-Hp) for detecting hydroperoxides was studied by fluorescence lifetime and transient absorption measurements. The MO calculations suggest the intramolecular charge transfer for Spy-Hp. The excited state lifetime of Spy-Hp is shorter than that of the oxidized form, which was caused by intramolecular fluorescence quenching. These results elucidate the mechanism of Spy-Hp for detecting hydroperoxides in biosamples.
Michael Addition of Active Methylene Compounds to α,β-Unsaturated Carbonyl Compounds under the Influence of Molecular Sieves in Dimethyl Sulfoxide
Authors: Kakinuma Tomoko , Chiba Ryoichi , Oriyama Takeshi
Published: November 2008

The Michael addition of active methylene compounds to α,β-unsaturated carbonyl compounds in the presence of MS 4A in dimethyl sulfoxide proceeds smoothly to afford the corresponding 1,4-addition products in good to high yields.
Morphological Modulation of Self-assembled Peptide by Aggregation-induced α-Helix/β-Sheet Transition
Authors: Tanaka Masayoshi , Ogura Kempei , Abiko Souhei , Koshikawa Naokiyo , Kinoshita Takatoshi
Published: November 2008

Poly(ethylene glycol) (PEG)-appended peptide with a binary sequence of hydrophobic and hydrophilic amino acids with 16 residues gave grain-like aggregate in aqueous solution. The peptide segment in the aggregate adopted β-sheet structure, while the peptide itself originally adopted α-helix structure. In the hydrophobic domain constructed by peptide segment, hydrogen bonding rearranged to give secondary structural transition. The α-helix/β-sheet transition simultaneously gave morphological transition from a grain-like state to a fibrous object.
Low-temperature Hydrogen-selective Catalytic Reduction of NOx on Pt/Sulfated-ZrO2 Catalysts under Excess Oxygen Conditions
Authors: Saito Makoto , Itoh Masahiro , Iwamoto Jun , Machida Ken-ichi
Published: November 2008

Platinum catalysts supported on sulfated zirconia powders highly promote the hydrogen-selective catalytic reduction (H2-SCR) of NOx at 100 °C with formation of ammonia intermediate species derived from protons of the sulfonate groups fixed as superacid sites on the surface, which are detected by in situ DRIFTs measurements.
Density Functional Theoretical Study on the pKa Values of Bipyridines
Authors: Joo Sang Woo , Jang Yun Hee , Hwang Sungu
Published: November 2008

The pKa values of bipyridines in aqueous solution were calculated using a density functional theoretical method in combination with the Poisson–Boltzmann continuum solvation model. Calculated pKa values correlates well with experimental results.
A Highly Stereoselective Knoevenagel Reaction of N-Tosylimines with Active Methylene Compounds in DMSO
Authors: Chiba Ryoichi , Oriyama Takeshi
Published: November 2008

In the presence of molecular sieves (MS) 4A in dimethyl sulfoxide (DMSO), a highly stereoselective Knoevenagel reaction of various N-tosylimines with active methylene compounds proceeded smoothly, producing the corresponding Knoevenagel products in high to excellent yields.
Cyclopropanation Reactions for the Synthesis of 2-Azabicyclo[4.1.0]heptane Derivatives with Nitric Oxide Synthase Inhibitory Activity
Authors: Suárez del Villar Irene , Gradillas Ana , Gómez-Ovalles Angel , Martínez-Murillo Ricardo , Martínez Alfredo , Pérez-Castells Javier
Published: November 2008

Synthesis of new bicyclic structures containing cyclopropanes, related to selective iNOS inhibitor ONO-1714, is described. We have evaluated the effect of the compounds obtained on the production of nitric oxide in lipopolysaccharide and interferon-gamma stimulated mouse peritoneal macrophages and on in vitro iNOS activity assays.
Sulfur-bridged Oligo(benzoic acid)s as a Novel Family of Metal Extractants
Authors: Morohashi Naoya , Nagata Kazutoshi , Tanaka Shinya , Ohba Yoshihiro , Hattori Tetsutaro
Published: November 2008

Sulfur-bridged phenol dimer and tetramer were converted into corresponding oligo(benzoic acid)s, which have high complexation ability toward lanthanide ions as revealed by solvent extraction study.
Anti-ferroelectric Banana Phase in a Bent-shaped Molecule with a Low Bend Angle of 60°
Authors: Lee Seng Kue , Shi Lu , Ishige Ryohei , Kang Sungmin , Tokita Masatoshi , Watanabe Junji
Published: November 2008

This paper presents the first example of an antiferroelectric banana phase in a bent molecule with a low bend angle of about 60°.
John Hunter's post-mortem examination of George Grenville (1712–1770)
Authors: Spigelman M , Berger L , Pinhasi R , Donoghue HD , Chaplin S
Published: November 2008

The Hunterian Museum at The Royal College of Surgeons of England contains approximately 3,500 specimens of human and comparative anatomy and pathology collected by the surgeon, John Hunter (1728–1793). A significant part of the collection comprises pathological specimens. These include specimens removed during surgery or as incidental findings from anonymous bodies being dissected during anatomical teaching. However, the majority comes from the bodies of patients on which Hunter performed post-mortem examinations. These include patients at St George's Hospital, where Hunter worked as a surgeon from 1768 until his death. A surprising number also come from the bodies of private patients. These were presumably removed with consent, at autopsies that would have taken place in the patient's own home and often with the patient's family or friends present.
Is there an alternative to the polyclinic?
Authors: Milford Christopher , Edwards Simon
Published: November 2008

The organisation of primary care could become more like barristers' chambers if recent proposals by the Royal College of General Practitioners (RCGP) become a reality. Published to coincide with the release of Lord Darzi's Next Stage Review report, it is seen by many as an alternative to the polyclinic model.
Bringing surgery closer to home
Authors: Towell Elaine
Published: November 2008

GPs with specialist intersts (GPSIs) have come in for a fair bit of criticism recently. Labelled as a new breed of GPs who would bridge the gap between primary and secondary care, they slotted nicely into the government's plans to bring care closer to home.
Energy potential of anaerobic digestion of wastes produced in Russia via biogas and microbial fuel cell technologies
Authors: Kalyuzhnyi Sergey
Published: November 2008

The well-known use of the microbiological process of anaerobic digestion (AD) to generate biogas (mixture of methane and CO2) is now widely implemented for the production of renewable energy worldwide. In Russia, however, this is not the case despite huge amounts of organic wastes (OW) suitable for AD. This paper firstly inventories major flows of OW from various sectors of the national economy (agriculture, industry, households, etc.) and estimates their biogas potential. Special attention is paid to existing bottlenecks and barriers to implementation of biogas technology given the Russian socioeconomic conditions. The second part of the paper is devoted to a new emerging technology based on AD-microbial fuel cells (MFCs). The current status of research in this field in Russia is reviewed in comparison with worldwide developments. The possible niches for implementation of MFC technology in Russia (e.g., wastewater treatment) are pointed out, including its complements to conventional biogas processes.
Glossary of terms related to kinetics, thermodynamics, and mechanisms of polymerization (IUPAC Recommendations 2008)
Authors: Penczek Stanisław , Moad Graeme
Published: November 2008

This document presents recommended definitions of basic terms related to polymerization processes. Recent developments relating to the kinetics, thermodynamics, and mechanisms of polymerization have necessitated the introduction of new terms and some revision or augmentation of terms previously defined in the Compendium of Chemical Terminology (the "Gold Book") or the IUPAC "Glossary of Basic Terms in Polymer Science".
Protocols on safety, efficacy, standardization, and documentation of herbal medicine (IUPAC Technical Report)
Authors: Mosihuzzaman M. , Choudhary M. Iqbal
Published: November 2008

This Technical Report compiles and analyzes the current scientific knowledge on herbal medicine and highlights the practical ways for ensuring the safety of herbal preparations and evaluating their claimed efficacy. Emphasis has been given to the methods for standardization of herbal medicine and the ways and means for moving forward to achieve the difficult goal of preparing herbal medicines of consistent quality and effects. Pragmatic approaches have been recommended to overcome the difficulties in (i) protecting intellectual property rights (IPR); (ii) producing safe, potent, standardized, and affordable herbal medicine; and (iii) documenting the knowledge base on herbal medicine in an easily accessible format.
Differential Excitability and Modulation of Striatal Medium Spiny Neuron Dendrites
Authors: Day Michelle , Wokosin David , Plotkin Joshua L. , Tian Xinyoung , Surmeier D. James
Published: November 2008

The loss of striatal dopamine (DA) in Parkinson's disease (PD) models triggers a cell-type-specific reduction in the density of dendritic spines in D2receptor-expressing striatopallidal medium spiny neurons (D2MSNs). How the intrinsic properties of MSN dendrites, where the vast majority of DA receptors are found, contribute to this adaptation is not clear. To address this question, two-photon laser scanning microscopy (2PLSM) was performed in patch-clamped mouse MSNs identified in striatal slices by expression of green fluorescent protein (eGFP) controlled by DA receptor promoters. These studies revealed that single backpropagating action potentials (bAPs) produced more reliable elevations in cytosolic Ca2+concentration at distal dendritic locations in D2MSNs than at similar locations in D1receptor-expressing striatonigral MSNs (D1MSNs). In both cell types, the dendritic Ca2+entry elicited by bAPs was enhanced by pharmacological blockade of Kv4, but not Kv1 K+channels. Local application of DA depressed dendritic bAP-evoked Ca2+transients, whereas application of ACh increased these Ca2+transients in D2MSNs, but not in D1MSNs. After DA depletion, bAP-evoked Ca2+transients were enhanced in distal dendrites and spines in D2MSNs. Together, these results suggest that normally D2MSN dendrites are more excitable than those of D1MSNs and that DA depletion exaggerates this asymmetry, potentially contributing to adaptations in PD models.
Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes
Authors: Lau Pierre , Verrier Jonathan D. , Nielsen Joseph A. , Johnson Kory R. , Notterpek Lucia , Hudson Lynn D.
Published: November 2008

MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile (“microRNAome”) contains 43 miRNAs whose expression dynamically changes during the transition from A2B5+oligodendrocyte progenitor cells to premyelinating GalC+cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3′ untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
From Fear to Safety and Back: Reversal of Fear in the Human Brain
Authors: Schiller Daniela , Levy Ifat , Niv Yael , LeDoux Joseph E. , Phelps Elizabeth A.
Published: November 2008

Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a “naive” safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.
Cholecystokinin Regulates Expression of Y2 Receptors in Vagal Afferent Neurons Serving the Stomach
Authors: Burdyga Galina , de Lartigue Guillaume , Raybould Helen E. , Morris Richard , Dimaline Rod , Varro Andrea , Thompson David G. , Dockray Graham J.
Published: November 2008

The intestinal hormones CCK and PYY3–36 inhibit gastric emptying and food intake via vagal afferent neurons. Here we report that CCK regulates the expression of Y2R, at which PYY3–36 acts. In nodose ganglia from rats fasted up to 48 h, there was a fivefold decrease of Y2R mRNA compared with rats fedad libitum; Y2R mRNA in fasted rats was increased by administration of CCK, and by refeeding through a mechanism sensitive to the CCK1R antagonist lorglumide. Antibodies to Y2R revealed expression in both neurons and satellite cells; most of the former (89 ± 4%) also expressed CCK1R. With fasting there was loss of Y2R immunoreactivity in CCK1R-expressing neurons many of which projected to the stomach, but not in satellite cells or neurons projecting to the ileum or proximal colon. Expression of a Y2R promoter-luciferase reporter (Y2R-luc) in cultured vagal afferent neurons was increased in response to CCK by 12.3 ± 0.1-fold and by phorbol ester (16.2 ± 0.4-fold); the response to both was abolished by the protein kinase C inhibitor Ro-32,0432. PYY3–36 stimulated CREB phosphorylation in rat nodose neurons after priming with CCK; in wild-type mice PYY3–36 increased Fos labeling in brainstem neurons but in mice null for CCK1R this response was abolished. Thus Y2R is expressed by functionally distinct subsets of nodose ganglion neurons projecting to the stomach and ileum/colon; in the former expression is dependent on stimulation by CCK, and there is evidence that PYY3–36 effects on vagal afferent neurons are CCK dependent.
Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans
Authors: Lee Michael C. , Zambreanu Laura , Menon David K. , Tracey Irene
Published: November 2008

Central sensitization (CS) refers to an increase in the excitability of spinal dorsal horn neurons that results from, and far outlasts the initiating nociceptive input. Here, functional magnetic resonance imaging was used to examine whether supraspinal activity might contribute to the maintenance of CS in humans. A crossover parametric design was used to distinguish and control for brain activity that is related to the consequence of increased pain experienced during CS. When the intensity of pain during CS and normal states were matched, only activity within the brainstem, including the mesencephalic pontine reticular formation, and the anterior thalami remained increased during CS. Further analyses revealed that activity in the isolated brainstem area correlated positively with the force of noxious stimulation only during CS, whereas activity in the isolated thalamic area was not modulated parametrically in either CS or normal states. Additionally, the mean activity in the isolated brainstem area was increased only during CS, whereas the mean activity in the isolated thalamic area was increased in both states, albeit less so in the normal state. Together, these findings suggest a specific role of the brainstem for the maintenance of CS in humans. Regarding brain areas related to the consequence of increased pain perception during CS, we found that only cortical activity, mainly in the primary somatosensory area, was significantly correlated with intensity of pain that was attributable to both the force of noxious stimulation used and state in which noxious stimulation was applied.
Constitutive Activity at the Cannabinoid CB1Receptor Is Required for Behavioral Response to Noxious Chemical Stimulation of TRPV1: Antinociceptive Actions of CB1 Inverse Agonists
Authors: Fioravanti Beatriz , De Felice Milena , Stucky Cheryl L. , Medler Karen A. , Luo Miaw-Chyi , Gardell Luis R. , Ibrahim Mohab , Malan T. Phil , Yamamura Henry I. , Ossipov Michael H. , King Tamara , Lai Josephine , Porreca Frank , Vanderah Todd W.
Published: November 2008

The potential modulation of TRPV1 nociceptive activity by the CB1receptor was investigated here using CB1wild-type (WT) and knock-out (KO) mice as well as selective CB1inverse agonists. No significant differences were detected in baseline thermal thresholds of ICR, CB1WT or CB1KO mice. Intraplantar capsaicin produced dose- and time-related paw flinch responses in ICR and CB1WT mice and induced plasma extravasation yet minimal responses were seen in CB1KO animals with no apparent differences in TRPV1 channel expression. Capsaicin-evoked CGRP release from spinal cord tissue and capsaicin-evoked action potentials on isolated skin-nerve preparation were significantly decreased in CB1KO mice. Pretreatment with intraplantar galanin and bradykinin, compounds known to sensitize TRPV1 receptors, restored capsaicin-induced flinching in CB1KO mice. The possibility that constitutive activity at the CB1receptor is required to maintain the TRPV1 receptor in a “sensitized” state was tested using CB1inverse agonists. The CB1inverse agonists elicited concentration-related inhibition of capsaicin-induced calcium influx in F-11 cells and produced dose-related inhibition of capsaicin-induced flinching in ICR mice. These data suggest that constitutive activity at the CB1receptor maintains the TRPV1 channel in a sensitized state responsive to noxious chemical stimuli. Treatment with CB1inverse agonists may promote desensitization of the channel resulting in antinociceptive actions against chemical stimulus modalities. These studies propose possible therapeutic exploitation of a novel mechanism providing pain relief by CB1inverse agonists.
Midbrain Dopaminergic Neurons and Striatal Cholinergic Interneurons Encode the Difference between Reward and Aversive Events at Different Epochs of Probabilistic Classical Conditioning Trials
Authors: Joshua Mati , Adler Avital , Mitelman Rea , Vaadia Eilon , Bergman Hagai
Published: November 2008

Midbrain dopaminergic neurons (DANs) typically increase their discharge rate in response to appetitive predictive cues and outcomes, whereas striatal cholinergic tonically active interneurons (TANs) decrease their rate. This may indicate that the activity of TANs and DANs is negatively correlated and that TANs can broaden the basal ganglia reinforcement teaching signal, for instance by encoding worse than predicted events. We studied the activity of 106 DANs and 180 TANs of two monkeys recorded during the performance of a classical conditioning task with cues predicting the probability of food, neutral, and air puff outcomes. DANs responded to all cues with elevations of discharge rate, whereas TANs depressed their discharge rate. Nevertheless, although dopaminergic responses to appetitive cues were larger than their responses to neutral or aversive cues, the TAN responses were more similar. Both TANs and DANs responded faster to an air puff than to a food outcome; however, DANs responded with a discharge elevation, whereas the TAN responses included major negative and positive deflections. Finally, food versus air puff omission was better encoded by TANs. In terms of the activity of single neurons with distinct responses to the different behavioral events, both DANs and TANs were more strongly modulated by reward than by aversive related events and better reflected the probability of reward than aversive outcome. Thus, TANs and DANs encode the task episodes differentially. The DANs encode mainly the cue and outcome delivery, whereas the TANs mainly encode outcome delivery and omission at termination of the behavioral trial episode.
Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate
Authors: Verrotti Alberto , Laus Melissa , Scardapane Alessandra , Franzoni Emilio , Chiarelli Francesco
Published: November 2008

Objective

This study evaluates the effects of long-term carbamazepine (CBZ) and valproate acid (VPA) therapy on thyroid function in epileptic children.

Design

A prospective study performed in 32 newly diagnosed pediatric patients, subdivided into two groups: 18 patients treated with CBZ and 14 patients treated with VPA. Thirty-two sex- and age- matched subjects served as controls.

Methods

Serum TSH, thyroxine (T4), triiodothyronine (T3), free thyroxine (fT4), free triiodothyronine (fT3), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Ab) were evaluated at baseline and at the 3rd, 6th, and 12th month in all patients and in the control group. A TRH stimulation test was performed in all epileptic patients at baseline and at the 3rd, 6th, and 12th month evaluations while in controls only baseline assessment was carried out.

Results

At baseline evaluation, thyroid function was normal in all epileptic children. After 3 months, CBZ-treated patients showed serum T4 and fT4 levels significantly lower than baseline evaluation and control subjects. Serum T4 and fT4 concentrations were unaffected by VPA monotherapy. Serum T3 and fT3 were normal in both CBZ-treated and VPA-treated patients. TRH test was normal in all patients. At 6th and 12th month evaluations, the same alterations were present in CBZ-treated patients while thyroid function remained normal in VPA-treated patients. TRH test responses were normal in all epileptic patients. TPO-Ab and TG-Ab were always absent in all patients.

Conclusions

Our data suggest that VPA monotherapy does not alter thyroid hormones. On the contrary, alterations of thyroid hormones occur in CBZ-treated children. However, the patients are euthyroid and thyroid hormone alterations are not associated with clinical or subclinical hypothyroidism.
Population Genetic Inference From Resequencing Data
Authors: Jiang Rong , Tavaré Simon , Marjoram Paul
Published: November 2008

This article is concerned with statistical modeling of shotgun resequencing data and the use of such data for population genetic inference. We model data produced by sequencing-by-synthesis technologies such as the Solexa, 454, and polymerase colony (polony) systems, whose use is becoming increasingly widespread. We show how such data can be used to estimate evolutionary parameters (mutation and recombination rates), despite the fact that the data do not necessarily provide complete or aligned sequence information. We also present two refinements of our methods: one that is more robust to sequencing errors and another that can be used when no reference genome is available.
Qualidade pós-colheita de pêssegos de cultivares e seleções produzidos na microrregião de Jaboticabal-SP
Authors: Mayer Newton Alex , Mattiuz Ben-Hur , Pereira Fernando Mendes
Published: November 2008

O objetivo deste trabalho foi avaliar a qualidade pós-colheita de pêssegos das cultivares 'Aurora-1' e 'Régis' e das seleções 'Jab 484' e 'Jab 694', produzidos na microrregião de Jaboticabal-SP. As plantas foram enxertadas no porta-enxerto 'Okinawa', propagado por sementes, mantidas em condições de campo em Argissolo Vermelho-Amarelo eutrófico de textura arenosa média e conduzidas no espaçamento 6 x 4m. No segundo e terceiro anos após o transplantio das mudas (2005 e 2006), procedeu-se à colheita dos frutos no estádio maduro, conforme a época de maturação e a coloração de cada genótipo. No laboratório, foram realizadas análises de coloração (luminosidade, ângulo de cor e cromaticidade) do epicarpo e mesocarpo, firmeza, teor de sólidos solúveis e acidez titulável, além do índice de maturação. Adotou-se o delineamento experimental inteiramente casualizado, com quatro tratamentos e seis repetições de quatro frutos. Nas condições experimentais adotadas, conclui-se que os frutos da cultivar Aurora-1 apresentam epicarpo avermelhado (menor ângulo de cor), menor acidez e maior índice de maturação (gosto); dentre os genótipos de dupla finalidade, as seleções 'Jab 484' e 'Jab 694' apresentam frutos com maiores teores de sólidos solúveis e acidez titulável, conferindo-lhes melhor característica para a industrialização.
Intensidade de poda verde em pessegueiro para controle da ferrugem Tranzschelia discolor (Fuckel) Tranzschel e Litvinov
Authors: Rodrigues Alessandro , Scarpare Filho João Alexio , Araújo João Paulo Campos de , Girardi Eduardo Augusto , Scarpare Fábio Vale
Published: November 2008

Com o objetivo de se avaliar o controle da ferrugem [Tranzschelia discolor (Fuckel) Tranzschel e Litvinov] em pessegueiro 'Flordaprince' [Prunus persica (L.) Batsch], duas intensidades de poda verde foram realizadas aos 45 dias após a colheita: poda leve e poda de renovação. O experimento foi realizado em condições de campo, no Departamento de Produção Vegetal da ESALQ-USP, em Piracicaba-SP, entre novembro de 2004 e janeiro de 2005. O delineamento experimental adotado foi inteiramente ao acaso, com dois tratamentos e doze réplicas. A parcela experimental correspondeu a duas plantas em espaçamento 3,0 x 1,2 m e conduzidas sob sistema de líder central. A avaliação de incidência e severidade de ferrugem foi realizada em folhas de quatro brotações por parcela, sendo duas por planta. As avaliações foram conduzidas de 33 a 81 dias após a poda verde, em intervalos de sete dias, utilizando-se de escala diagramática adaptada para a ferrugem. Os dados referentes à incidência e severidade de ferrugem foram submetidos, respectivamente, ao teste exato de Fisher e ao teste de Wilcoxon. A incidência e a severidade de ferrugem aumentaram com a idade das folhas, independentemente do tipo de poda verde empregada, atingindo, respectivamente, 81,95% das folhas e 1,43% de área foliar lesionada, aos 81 dias após a poda verde. A poda de renovação não reduziu os níveis de ferrugem em pessegueiro 'Flordaprince' em relação à poda leve, a partir dos 40 dias após a poda verde.
Reação de genótipos de maracujazeiro-amarelo ao Colletotrichum gloeosporioides
Authors: Martins Irene , Peixoto José Ricardo , Junqueira Nilton Vilela Tadeu , Mello Sueli Corrêa Marques de
Published: November 2008

O presente trabalho foi desenvolvido em casa de vegetação, na Estação Biológica da Universidade de Brasília, com objetivo de avaliar genótipos de maracujazeiro-amarelo frente ao fungo C. gloeosporioides, agente causal da antracnose. Para inoculação dos genótipos, utilizou-se uma suspensão contendo 5x10(6) esporos/mL do patógeno, depositados sobre ferimentos preestabelecidos com auxílio de escova de aço de cerdas finas. A primeira avaliação foi realizada 20 dias após a inoculação, e as demais, a intervalos de 7 dias, encerrando-se na sétima avaliação, aos 62 dias. Determinaram-se a incidência e a severidade da antracnose, com auxílio de uma escala graduada de notas, onde 1 = ausência de sintomas e 7 = desfolha. Consideraram-se as plantas como: Resistentes (R), com notas médias < 2; Moderadamente Resistentes (MR), com notas médias > 2 e < 3; Suscetíveis (S), com notas médias > 3 e < 4; e Altamente Suscetíveis (AS), com notas médias > 4. No geral, dois genótipos foram classificadas como Moderadamente Resistentes; oito, como Suscetíveis e 62, como Altamente Suscetíveis.
Avaliação agronômica de cultivares de videiras apirenas na região de Jaíba, Minas Gerais
Authors: Feldberg Nelson Pires , Dias Mário Sérgio Carvalho , Regina Murillo de Albuquerque
Published: November 2008

Atualmente, há interesse crescente no cultivo de cultivares de uvas apirenas no Brasil, devido ao aumento na demanda e ao alto valor recebido pelos seus frutos, além da possibilidade de produção em épocas de pouca oferta no mercado mundial. Este trabalho teve o objetivo de introduzir e avaliar o desempenho agronômico das cultivares Catalunha, Sultanina, Crimson Seedless e Superior Seedless enxertadas sobre 'IAC 572 Jales'. O experimento foi realizado na Fazenda Experimental da EPAMIG, em Mocambinho, distrito de Jaíba-MG, em delineamento inteiramente casualizado, com sete repetições. Foram analisados a fertilidade de gemas, o número e a massa de cachos, e o número e a massa de ramos. O ciclo, da poda à colheita dos cachos, foi de 97 dias para 'Superior Seedless', 104 dias para 'Sultanina', 106 dias para 'Catalunha' e 125 dias para 'Crimson Seedless'. As melhores produtividades foram obtidas nas safras com podas realizadas no primeiro semestre de cada ano, para todas as cultivares. 'Catalunha' apresentou os melhores resultados quanto ao número de cachos por planta e fertilidade de gemas, atingindo produtividade média de 19,0t/ha/ano. A cultivar Catalunha pode ser indicada para o cultivo em Jaíba-MG, sendo, entretanto, necessários novos estudos de manejo para o aumento da fertilidade de gemas de 'Crimson Seedless', 'Sultanina' e 'Superior Seedless'.