bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to carbaryl leads to ultrastructural changes and alters activity of antioxidant enzymes in Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Adamski Zbigniew
Published: August 2007

Abstract. The toxic effect of carbamate insecticide carbaryl on Spodoptera exigua (Lepidoptera: Noctuidae) larvae was examined. Insects appeared to be highly sensitive to it; numerous malfunctions and malformations were observed. The first ultrastructural alterations, including biological membrane swelling, nuclear condensation, and disintegration, and abnormalities around the mitochondria were observed even before massive mortality was noted. Scanning electron microscopy revealed changes in cuticle. Carbaryl depleted the wet weight of fat body mass and changed (in most of the cases elevated) the activity of antioxidant enzymes. The majority of these malformations are rather non‐specific and are common among animals exposed to xenobiotics. However, they all suggest serious disruptions in metabolism, in addition to indicating that reactive oxygen species may play an important role in the toxic effect of carbaryl.
Lake Nuga Nuga: a Levee‐dammed Lake in Central Queensland, Australia
Authors: FINLAYSON BRIAN , KENYON CHRISTINE
Published: August 2007

Lake Nuga Nuga is a levee‐dammed lake in the dry sub‐humid tropics of the Fitzroy Basin in Central Queensland, Australia, that has expanded significantly since it was first mapped in 1866. 210Pb dating of a sediment core from the lake indicates that the rate of sedimentation has been constant for the past 67 years at 3 mm yr−1 despite widespread clearing and land use intensification in the catchment during that time. Pollen analysis confirms this and shows that there was little change in vegetation during the early settlement period (1863–1962), but the intensification of land use that started in the early 1960s brought about a dramatic change in the vegetation communities. This study demonstrates that while sediment production may be significantly impacted by land‐use activities, sediment delivery is primarily controlled by topography.
Race, Gender, and Class in the Persistence of the Mariel Stigma Twenty Years after the Exodus from Cuba
Authors: Fernández Gastón A.
Published: August 2007

The study examines the mediating effects of gender, race, and class in the Mariel Cuban immigrant adaptation process. It explores the significance of the Mariel identity by comparing the experiences of pre-1980 arrivals with those of the Mariel cohort (1980–1981) and post-Mariel arrivals (1982–1990, 1990–2000). The central question of the study is the extent to which the Marielitos' experience as a group with stigmatization and being labeled as “different” and pathological has persisted in having a different effect on their adaptation to the U.S. from that of other Cuban arrivals before and after Mariel. This study bases its definition of stigma on sociologically grounded theoretical orientation of the construction of a social identity in which a dominant group(s) attribute an undesired difference from what was anticipated to an out-group such that it leads to varieties of discrimination that reduce one's life chances.
The Reshaping of Mexican Labor Exports under NAFTA: Paradoxes and Challenges
Authors: Delgado-Wise Raúl , Covarrubias Humberto Márquez
Published: August 2007

From the perspective of the political economy of development, this article analyzes the role played by Mexican labor in the U.S. productive restructuring process under the aegis of the North American Free Trade Agreement. By conceptualizing the labor export–led model it dissects three basic mechanisms of regional economic integration: maquiladoras, disguised maquilas, and labor migration. Not only does this analytical framework cast light on the contributions made by Mexican migrants to the economies of the United States and Mexico, it also reveals two paradoxes: the broadening of the socioeconomic asymmetries between the two countries, and increased socioeconomic dependence on remittances in Mexico.
Changes in the Initial Destinations and Redistribution of Canada's Major Immigrant Groups: Reexamining the Role of Group Affinity
Authors: Hou Feng
Published: August 2007

This study examines to what extent Canada's recent immigrants have altered their geographic concentration over time, with a view of determining the role of preexisting immigrant communities in immigrants' locational choices, looking specifically at community size. The results show a large increase in concentration levels at the initial destination among major immigrant groups throughout the 1970s and 1980s, and a much smaller increase in the following decade. However, redistribution after immigration was generally small-scale and had inconsistent effects on changing concentration at initial destinations among immigrant groups and across arrival cohorts within an immigrant group. Finally, this study finds that the size of the preexisting immigrant community is not a significant factor in immigrant locational choice when location fixed effects are accounted for.
Genes and Spleens: Property, Contract, or Privacy Rights in the Human Body?
Authors: Rao Radhika
Published: August 2007

The legal status of the human body is hotly contested, yet the law of the body remains in a state of confusion and chaos. Sometimes the body is treated as an object of property, sometimes it is dealt with under the rubric of contract, and sometimes it is not conceived as property at all, but rather as the subject of privacy rights. Which body of law should become the law of the body? This question is even more pressing in the context of current biomedical research, which permits commodification and commercialization of the body by everyone except the person who provides the “raw materials.” The lack of property protection for tangible parts of the human body is in stark contrast to the extensive protection granted to intellectual property in the body in the form of patents upon human genes and cell lines. Moreover, even courts that reject ownership claims on the part of those who supply body parts appear willing to grant property rights to scientists, universities, and others who use those body parts to conduct research and create products.
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast
Authors: Torres Eduardo M. , Sokolsky Tanya , Tucker Cheryl M. , Chan Leon Y. , Boselli Monica , Dunham Maitreya J. , Amon Angelika
Published: August 2007

Aneuploidy is a condition frequently found in tumor cells, but its effect on cellular physiology is not known. We have characterized one aspect of aneuploidy: the gain of extra chromosomes. We created a collection of haploid yeast strains that each bear an extra copy of one or more of almost all of the yeast chromosomes. Their characterization revealed that aneuploid strains share a number of phenotypes, including defects in cell cycle progression, increased glucose uptake, and increased sensitivity to conditions interfering with protein synthesis and protein folding. These phenotypes were observed only in strains carrying additional yeast genes, which indicates that they reflect the consequences of additional protein production as well as the resulting imbalances in cellular protein composition. We conclude that aneuploidy causes not only a proliferative disadvantage but also a set of phenotypes that is independent of the identity of the individual extra chromosomes.
Coherent Optical Spectroscopy of a Strongly Driven Quantum Dot
Authors: Xu Xiaodong , Sun Bo , Berman Paul R. , Steel Duncan G. , Bracker Allan S. , Gammon Dan , Sham L. J.
Published: August 2007

Quantum dots are typically formed from large groupings of atoms and thus may be expected to have appreciable many-body behavior under intense optical excitation. Nonetheless, they are known to exhibit discrete energy levels due to quantum confinement effects. We show that, like single-atom or single-molecule two- and three-level quantum systems, single semiconductor quantum dots can also exhibit interference phenomena when driven simultaneously by two optical fields. Probe absorption spectra are obtained that exhibit Autler-Townes splitting when the optical fields drive coupled transitions and complex Mollow-related structure, including gain without population inversion, when they drive the same transition. Our results open the way for the demonstration of numerous quantum level–based applications, such as quantum dot lasers, optical modulators, and quantum logic devices.
Structure and Function of an Essential Component of the Outer Membrane Protein Assembly Machine
Authors: Kim Seokhee , Malinverni Juliana C. , Sliz Piotr , Silhavy Thomas J. , Harrison Stephen C. , Kahne Daniel
Published: August 2007

Integral β-barrel proteins are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. The machine that assembles these proteins contains an integral membrane protein, called YaeT in
Escherichia coli
, which has one or more polypeptide transport–associated (POTRA) domains. The crystal structure of a periplasmic fragment of YaeT reveals the POTRA domain fold and suggests a model for how POTRA domains can bind different peptide sequences, as required for a machine that handles numerous β-barrel protein precursors. Analysis of POTRA domain deletions shows which are essential and provides a view of the spatial organization of this assembly machine.
Detection of Near-Atmospheric Concentrations of CO
2
by an Olfactory Subsystem in the Mouse
Authors: Hu Ji , Zhong Chun , Ding Cheng , Chi Qiuyi , Walz Andreas , Mombaerts Peter , Matsunami Hiroaki , Luo Minmin
Published: August 2007

Carbon dioxide (CO
2
) is an important environmental cue for many organisms but is odorless to humans. It remains unclear whether the mammalian olfactory system can detect CO
2
at concentrations around the average atmospheric level (0.038%). We demonstrated the expression of carbonic anhydrase type II (CAII), an enzyme that catabolizes CO
2
, in a subset of mouse olfactory neurons that express guanylyl cyclase D (GC-D
+
neurons) and project axons to necklace glomeruli in the olfactory bulb. Exposure to CO
2
activated these GC-D
+
neurons, and exposure of a mouse to CO
2
activated bulbar neurons associated with necklace glomeruli. Behavioral tests revealed CO
2
detection thresholds of ∼0.066%, and this sensitive CO
2
detection required CAII activity. We conclude that mice detect CO
2
at near-atmospheric concentrations through the olfactory subsystem of GC-D
+
neurons.
Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKMζ
Authors: Shema Reut , Sacktor Todd Charlton , Dudai Yadin
Published: August 2007

Little is known about the neuronal mechanisms that subserve long-term memory persistence in the brain. The components of the remodeled synaptic machinery, and how they sustain the new synaptic or cellwide configuration over time, are yet to be elucidated. In the rat cortex, long-term associative memories vanished rapidly after local application of an inhibitor of the protein kinase C isoform, protein kinase M zeta (PKMζ). The effect was observed for at least several weeks after encoding and may be irreversible. In the neocortex, which is assumed to be the repository of multiple types of long-term memory, persistence of memory is thus dependent on ongoing activity of a protein kinase long after that memory is considered to have consolidated into a long-term stable form.
Development and Validation of an Ovine Progressive Pneumonia Virus Quantitative PCR
Authors: Herrmann-Hoesing Lynn M. , White Stephen N. , Lewis Gregory S. , Mousel Michelle R. , Knowles Donald P.
Published: August 2007

Ovine progressive pneumonia virus (OPPV) infects at least one sheep in 81% of U.S. sheep flocks, as determined by serology, and can cause viral mastitis, arthritis, dyspnea, and cachexia. Diagnostic tests that quantify OPPV proviral load in peripheral blood leukocytes (PBL) provide an additional method for identification of infected sheep and may help to further understanding of the pathogenesis of OPPV-induced disease. In this study, we compared a new OPPV real-time quantitative PCR (qPCR) assay specific for the transmembrane region of the envelope gene (
tm
) with a competitive inhibition enzyme-linked immunosorbent assay (cELISA) using 396 PBL samples and sera from Idaho sheep. The OPPV qPCR had a positive concordance of 96.2% ± 2.3% and a negative concordance of 97.7% ± 2.5% compared to the cELISA, with a kappa value of 0.93, indicating excellent agreement between the two tests. In addition, the presence of
tm
in the three OPPV qPCR-positive and cELISA-negative sheep and in 15 sheep with different OPPV proviral loads was confirmed by cloning and sequencing. These data indicate that the OPPV qPCR may be used as a supplemental diagnostic tool for OPPV infection and for measurement of viral load in PBLs of infected sheep.
Serum Immunoglobulin G Antibodies to the GOR Autoepitope Are Present in Patients with Occult Hepatitis C Virus (HCV) Infection despite Lack of HCV-Specific Antibodies
Authors: Quiroga Juan A. , Castillo Inmaculada , Bartolomé Javier , Carreño Vicente
Published: August 2007

Antibody responses to the GOR autoepitope are frequently detected among anti-hepatitis C virus (anti-HCV)-positive patients with chronic hepatitis. Sera from 110 anti-HCV-negative patients with occult HCV infection, as diagnosed by detection of HCV RNA in hepatic tissue, were investigated for GOR antibody reactivity. A positive test for anti-GOR immunoglobulin G (IgG) was found for 22 (20%) of them. The frequency and titers of anti-GOR IgG were significantly lower than those in chronic hepatitis C patients (70/110, 63.6%;
P
< 0.001). Anti-GOR IgG was not detected in any of the 120 patients with HCV-unrelated liver disease. The anti-GOR IgG assay showed specificity and sensitivity values of 100% and 20%, respectively, among the sera from patients with occult HCV infection; the positive and negative predictive values were 100% and 44.3%, respectively. None of the clinical, laboratory, or histological characteristics of the patients with occult HCV infection were different according to GOR antibody status, except that the percentage of HCV RNA-positive hepatocytes was significantly greater (
P
= 0.042) in patients with occult HCV infection who tested positive for anti-GOR IgG. In conclusion, serum anti-GOR IgG is present in patients with occult HCV infection, despite a lack of detectable HCV-specific antibodies as determined by commercial tests. Testing for anti-GOR IgG in patients in whom HCV RNA is not detected in their sera may help with the identification of a subset of patients with occult HCV infection without the need to perform a liver biopsy.
Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study
Authors: Banus Sander , Bottema Renske W. B. , Siezen Christine L. E. , Vandebriel Rob J. , Reimerink Johan , Mommers Monique , Koppelman Gerard H. , Hoebee Barbara , Thijs Carel , Postma Dirkje S. , Kimman Tjeerd G. , Stelma Foekje F.
Published: August 2007

We examined the association between haplotype tagging single-nucleotide polymorphisms in
TLR4
and the pertussis toxin-specific immunoglobulin G response after whole-cell pertussis (wP) vaccination in 515 1-year-old children from the KOALA study. A lower titer was associated with the minor allele of rs2770150, supporting a role for Toll-like receptor 4 in the antibody response to wP vaccination.
Pulsed-Field Gel Electrophoresis, Pertactin, Pertussis Toxin S1 Subunit Polymorphisms, and Surfaceome Analysis of Vaccine and Clinical
Bordetella pertussis
Strains
Authors: Bottero Daniela , Gaillard María Emilia , Fingermann Matías , Weltman Gabriela , Fernández Julieta , Sisti Federico , Graieb Augusto , Roberts Roy , Rico Osvaldo , Ríos Gustavo , Regueira Mabel , Binsztein Norma , Hozbor Daniela
Published: August 2007

To add new insight to our previous work on the molecular epidemiology of
Bordetella pertussis
in Argentina, the
prn
and
ptxS1
gene sequences and pulsed-field gel electrophoresis (PFGE) profiles of 57 clinical isolates obtained during two periods, 1969 to 1989 and 1997 to 2006, were analyzed. Non-vaccine-type
ptxS1A
was detected in isolates obtained since 1969. From 1989 on, a shift of predominance from the vaccine
prn1
type to the nonvaccine
prn2
type was observed. This was also reflected in a transition of PFGE group IV to group VI. These results show that nonvaccine
B. pertussis
strains are currently circulating. To analyze whether the observed genomic divergences between vaccine strains and clinical isolates have functional implications, protection assays using the intranasal mouse challenge model were performed. For such experiments, the clinical isolate
B. pertussis
106 was selected as representative of circulating bacteria, since it came from the major group of the PFGE dendrogram (PFGE group VI). Groups of mice were immunized either with diphtheria-tetanus-whole-cell pertussis vaccine (
ptxS1B prn1
) or a vaccine prepared by us containing
B. pertussis
106. Immunized mice were then challenged with a
B. pertussis
vaccine strain (Tohama, harboring
ptxS1B
and
prn1
) or the clinical isolate
B. pertussis
106 (
ptxS1A prn2
). An adequate bacterial-elimination rate was observed only when mice were immunized and challenged with the same kind of strain. For further characterization, comparative proteomic profiling of enriched membrane proteins was done using three vaccine strains and the selected
B. pertussis
106 clinical isolate. By matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis, a total of 54 proteins were identified. This methodology allowed us to detect differing proteins among the four strains studied and, in particular, to distinguish the three vaccine strains from each other, as well as the vaccine strains from the clinical isolate. The differing proteins observed have cellular roles associated with amino acid and carbohydrate transport and metabolism. Some of them have been proposed as novel vaccine candidate proteins for other pathogens. Overall, the global strategy described here is presented as a good tool for the development of next-generation acellular vaccines.
Case of Keratitis Caused by
Aspergillus tamarii
Authors: Kredics László , Varga János , Kocsubé Sándor , Dóczi Ilona , Samson Robert A. , Rajaraman Revathi , Narendran Venkatapathy , Bhaskar Madhavan , Vágvölgyi Csaba , Manikandan Palanisamy
Published: August 2007

We report a case of
Aspergillus tamarii
keratitis. Ocular injury was known to be a predisposing factor. Topical natamycin and econazole treatment and subsequent systemic ketoconazole treatment proved effective. The isolate was identified by morphological characteristics and sequence analysis as
A. tamarii
, a member of
Aspergillus
section
Flavi
not hitherto reported from keratomycosis.
Seroepidemiology of Human Bocavirus in Hokkaido Prefecture, Japan
Authors: Endo Rika , Ishiguro Nobuhisa , Kikuta Hideaki , Teramoto Shinobu , Shirkoohi Reza , Ma Xiaoming , Ebihara Takashi , Ishiko Hiroaki , Ariga Tadashi
Published: August 2007

A new human virus, provisionally named human bocavirus (HBoV), was discovered by Swedish researchers in 2005. A new immunofluorescence assay using
Trichoplusia ni
insect cells infected with a recombinant baculovirus expressing the VP1 protein of HBoV was developed, and the levels of immunoglobulin G antibody to the VP1 protein of HBoV in serum samples were measured. The overall seroprevalence rate of antibodies against the VP1 protein of HBoV in a Japanese population aged from 0 months to 41 years was 71.1% (145 of 204). The seropositive rate was lowest in the age group of 6 to 8 months and gradually increased with age. All of the children had been exposed to HBoV by the age of 6 years. A rise in titers of antibody against the VP1 protein of HBoV during the convalescent phase was observed for four patients with lower respiratory tract infections, and HBoV DNA was detected in nasopharyngeal swab and serum samples from all four patients. These results suggest that HBoV is a ubiquitous virus acquired early in life and that HBoV might play a role in the course of lower respiratory tract infections.
Strategic Approach To Produce Low-Cost, Efficient, and Stable Competitive Internal Controls for Detection of RNA Viruses by Use of Reverse Transcription-PCR
Authors: Villanova Gabriela V. , Gardiol Daniela , Taborda Miguel A. , Reggiardo Virginia , Tanno Hugo , Rivadeneira Emilia D. , Perez Germán R. , Giri Adriana A.
Published: August 2007

Molecular diagnostics based on reverse transcription (RT)-PCR are routinely complicated by the lack of stable internal controls, leading to falsely negative results. We describe a strategy to produce a stable competitive internal control (CIC) based on a Qβ phage derivative (recombinant Qβ [rQβ]) bearing primers KY78 and KY80, which are widely used in the detection of hepatitis C virus (HCV). rQβ was RNase resistant and stable at 4°C for 452 days in SM medium (0.1 M NaCl, 8 mM MgSO
4
·7H
2
O, 50 mM Tris HCl [pH 7.5], 2% gelatin) and for 125 days after lyophilization and reconstitution. rQβ performance as a CIC was evaluated. rQβ was added to HCV-positive samples, followed by RNA extraction and a CIC-HCV RT-PCR assay. This method combines RT-PCR, liquid hybridization with nonradioactive probes, and enzyme immunoanalysis. No influence of the CIC on qualitative HCV detection was observed independently of viral load, and results had high concordance with those of commercial kits. In conclusion, we describe a versatile, low-cost alternative strategy to armored RNA technology that can be adapted for detection or real-time applications of any RNA target. Moreover, the CIC reported here is an essential reagent for HCV screening in blood banks in resource-limited settings.
Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication
Authors: Moser Lindsey A. , Carter Michael , Schultz-Cherry Stacey
Published: August 2007

Astrovirus infection in a variety of species results in an age-dependent diarrhea; however, the means by which astroviruses cause diarrhea remain unknown. Studies of astrovirus-infected humans and turkeys have demonstrated few histological changes and little inflammation during infection, suggesting that intestinal damage or an overzealous immune response is not the primary mediator of astrovirus diarrhea. An alternative contributor to diarrhea is increased intestinal barrier permeability. Here, we demonstrate that astrovirus increases barrier permeability in a Caco-2 cell culture model system following apical infection. Increased permeability correlated with disruption of the tight-junction protein occludin and decreased the number of actin stress fibers in the absence of cell death. Additionally, permeability was increased when monolayers were treated with UV-inactivated virus or purified recombinant human astrovirus serotype 1 capsid in the form of virus-like particles. Together, these results demonstrate that astrovirus-induced permeability occurs independently of viral replication and is modulated by the capsid protein, a property apparently unique to astroviruses. Based on these data, we propose that the capsid contributes to diarrhea in vivo.
Early Antibodies Specific for the Neutralizing Epitope on the Receptor Binding Subunit of the Lymphocytic Choriomeningitis Virus Glycoprotein Fail To Neutralize the Virus
Authors: Eschli Bruno , Zellweger Raphaël M. , Wepf Alexander , Lang Karl S. , Quirin Katharina , Weber Jacqueline , Zinkernagel Rolf M. , Hengartner Hans
Published: August 2007

Lymphocytic choriomeningitis virus (LCMV) is a murine arenavirus whose glycoprotein consists of a transmembrane subunit (GP-2) and a receptor-binding subunit (GP-1). LCMV-neutralizing antibodies (nAbs) are directed against a single site on GP-1 and occur 1 month after the infection of cytotoxic-T-lymphocyte (CTL) deficient mice. In wild-type mice, however, CTLs control early infection, and weak nAb titers emerge very late (after 70 to 150 days) if at all. Production of recombinant GP-1 in native conformation enabled us to study the emergence of GP-1-binding antibodies directed against the neutralizing epitope. By combining binding and neutralization assays, we correlated the development of binding antibodies versus nAbs in wild-type and CTL-deficient mice after infection with different LCMV doses. We found that wild-type mice developed GP-1-specific antibodies already by day 8 after exposure to high but not low doses, demonstrating that naive GP-1-specific B cells were infrequent. Furthermore, the induced antibodies bound to the neutralizing GP-1 epitope but failed to neutralize the virus and therefore were of low affinity. In CTL-deficient mice, where massive viremia quickly levels initial differences in viral load, low and high doses induced low-affinity non-neutralizing GP-1-binding antibodies with kinetics similar to high-dose-infected wild-type mice. Only in CTL-deficient mice, however, the GP-1-specific antibodies developed into nAbs within 1 month. We conclude that LCMV uses a dual strategy to evade nAb responses in wild-type mice. First, LCMV exploits a “hole” in the murine B-cell repertoire, which provides only a small and narrow initial pool of low-affinity GP-1-specific B cells. Second, affinity maturation of the available low-affinity non-neutralizing antibodies is impaired.
Mechanisms of Late Restriction Induced by an Endogenous Retrovirus
Authors: Arnaud Frederick , Murcia Pablo R. , Palmarini Massimo
Published: August 2007

The host has developed during evolution a variety of “restriction factors” to fight retroviral infections. We investigated the mechanisms of a unique viral block acting at late stages of the retrovirus replication cycle. The sheep genome is colonized by several copies of endogenous retroviruses, known as enJSRVs, which are highly related to the oncogenic jaagsiekte sheep retrovirus (JSRV). enJS56A1, one of the enJSRV proviruses, can act as a restriction factor by blocking viral particles release of the exogenous JSRV. We show that in the absence of enJS56A1 expression, the JSRV Gag (the retroviral internal structural polyprotein) targets initially the pericentriolar region, in a dynein and microtubule-dependent fashion, and then colocalizes with the recycling endosomes. Indeed, by inhibiting the endocytosis and trafficking of recycling endosomes we hampered JSRV exit from the cell. Using a variety of approaches, we show that enJS56A1 and JSRV Gag interact soon after synthesis and before pericentriolar/recycling endosome targeting of the latter. The transdominant enJS56A1 induces intracellular Gag accumulation in microaggregates that colocalize with the aggresome marker GFP-250 but develop into bona fide aggresomes only when the proteasomal machinery is inhibited. The data argue that dominant-negative proteins can modify the overall structure of Gag multimers/viral particles hampering the interaction of the latter with the cellular trafficking machinery.
Cyclodextrins Inhibit Replication of Scrapie Prion Protein in Cell Culture
Authors: Prior Marguerite , Lehmann Sylvain , Sy Man-Sun , Molloy Brendan , McMahon Hilary E. M.
Published: August 2007

Prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal host-encoded protein, PrPC, to an abnormal, disease-causing form, PrPSc. This paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein PrPScto undetectable levels in scrapie-infected neuroblastoma cells. Beta-cyclodextrin removed PrPScfrom the cells at a concentration of 500 μM following 2 weeks of treatment. Structure activity studies revealed that antiprion activity was dependent on the size of the cyclodextrin. The half-maximal inhibitory concentration (IC50) for beta-cyclodextrin was 75 μM, whereas α-cyclodextrin, which possessed less antiprion activity, had an IC50of 750 μM. This report presents cyclodextrins as a new class of antiprion compound. For decades, the pharmaceutical industry has successfully used cyclodextrins for their complex-forming ability; this ability is due to the structural orientation of the glucopyranose units, which generate a hydrophobic cavity that can facilitate the encapsulation of hydrophobic moieties. Consequently, cyclodextrins could be ideal candidates for the treatment of prion diseases.
Point, Counterpoint: The Evolution of Pathogenic Viruses and their Human Hosts
Authors: Worobey Michael , Bjork Adam , Wertheim Joel O.
Published: August 2007

Viral pathogens play a prominent role in human health owing to their ability to rapidly evolve creative new ways to exploit their hosts. As elegant and deceptive as many viral adaptations are, humans and their ancestors have repeatedly answered their call with equally impressive adaptations. Here we argue that the coevolutionary arms race between humans and their viral pathogens is one of the most important forces in human molecular evolution, past and present. With a focus on HIV-1 and other RNA viruses, we highlight recent developments in our understanding of the human innate and adaptive immune systems and how the selective pressures exerted by viruses have shaped the human genome. We also discuss how the antiviral function of cellular machinery like RNAi and APOBEC3G blur the lines between innate and adaptive immunity. The remarkable power of natural selection is revealed in each host-pathogen arms race examined.
A novel method using fluorescence microscopy for real-time assessment of ATP release from individual cells
Authors: Corriden Ross , Insel Paul A. , Junger Wolfgang G.
Published: August 2007

Many cell types release ATP in response to mechanical or biochemical stimulation. The mechanisms responsible for this release, however, are not well understood and may differ among different cell types. In addition, there are numerous difficulties associated with studying the dynamics of ATP release immediately outside the cell membrane. Here, we report a new method that allows the visualization and quantification of ATP release by fluorescence microscopy. Our method utilizes a two-enzyme system that generates NADPH when ATP is present. NADPH is a fluorescent molecule that can be visualized by fluorescence microscopy using an excitation wavelength of 340 nm and an emission wavelength of 450 nm. The method is capable of detecting ATP concentrations <1 μM and has a dynamic range of up to 100 μM. Using this method, we visualized and quantified ATP release from human polymorphonuclear leukocytes and Jurkat T cells. We show that upon cell stimulation, the concentrations of ATP can reach levels of up to 80 μM immediately outside of the cell membrane. This new method should prove useful for the study of the mechanisms of release and functional role of ATP in various cell systems, including individual cells.
Mast cell-mediated long-lasting increases in excitability of vagal C fibers in guinea pig esophagus
Authors: Yu Shaoyong , Kollarik Marian , Ouyang Ann , Myers Allen C. , Undem Bradley J.
Published: August 2007

Several esophageal pathologies are associated with an increased number of mast cells in the esophageal wall. We addressed the hypothesis that activation of esophageal mast cells leads to an increase in the excitability of local sensory C fibers. Guinea pigs were actively sensitized to ovalbumin. The mast cells in the esophagus were selectively activated ex vivo by superfusion with ovalbumin. Action potential discharge in guinea pig vagal nodose esophageal C-fiber nerve endings was monitored in the isolated (ex vivo) vagally innervated esophagus by extracellular recordings. Ovalbumin activated esophageal mast cells, leading to the rapid release of ∼20% of the tissue histamine stores. This was associated with a consistent and significant increase in excitability of the nodose C fibers as reflected in a two- to threefold increase in action potential discharge frequency evoked by mechanical (increases in intraluminal pressure) stimulation. The increase in excitability persisted unchanged for at least 90 min (longest time period tested) after ovalbumin was washed from the tissue. This effect could be prevented by the histamine H1 receptor antagonist pyrilamine, but once the increase in excitability occurred, it persisted in the nominal absence of histamine and could not be reversed even with large concentrations of the histamine receptor antagonist. In conclusion, activation of esophageal mast cells leads to a pronounced and long-lived increase in nociceptive C-fiber excitability such that any sensation or reflex evoked via the vagal nociceptors will likely be enhanced. The effect is initiated by histamine acting via H1 receptor activation and maintained in the absence of the initiating stimulus.
Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus
Authors: Ducsay Charles A. , Hyatt Kim , Mlynarczyk Malgorzata , Root Brandon K. , Kaushal Kanchan M. , Myers Dean A.
Published: August 2007

We previously communicated that long-term hypoxia (LTH) resulted in a selective reduction in plasma epinephrine following acute stress in fetal sheep. The present study tested the hypothesis that LTH selectively reduces adrenomedullary expression of phenylethanolamine-N-methyltransferase (PNMT), the rate-limiting enzyme for epinephrine synthesis. We also examined the effect of LTH on adrenomedullary nicotinic, muscarinic, and glucocorticoid receptor (GR) expression. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dGA); adrenomedullary tissue was collected from LTH and age-matched, normoxic control fetuses at 139–141 dGA. Contrary to our hypothesis, in addition to PNMT, adrenomedullary expression (mRNA, protein) of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were reduced in the LTH fetus. Immunocytochemistry indicated that TH and DBH expression was lower throughout the medulla, while PNMT appeared to reflect a reduction in PNMT-expressing cells. Nicotinic receptor alpha 1, 2, 3, 5, 6, 7, beta 1, 2, and 4 subunits were expressed in the medulla of LTH and control fetuses. Messenger RNA for alpha 1 and 7 and beta 1 and 2 subunits was lower in LTH fetuses. Muscarinic receptors M1, M2, and M3 as well as the GR were also expressed, and no differences were noted between groups. In summary, LTH in fetal sheep has a profound effect on expression of key enzymes mediating adrenomedullary catecholamine synthesis. Further, LTH impacts nicotinic receptor subunit expression potentially altering cholinergic neurotransmission within the medulla. These findings have important implications regarding fetal cardiovascular and metabolic responses to stress in the LTH fetus.
Proinflammatory and proliferative responses of human proximal tubule cells to PAR-2 activation
Authors: Vesey David A. , Kruger Wade A. , Poronnik Philip , Gobé Glenda C. , Johnson David W.
Published: August 2007

Despite the abundant expression of protease-activated receptor (PAR)-2 in the kidney, its relevance to renal physiology is not well understood. A role for this receptor in inflammation and cell proliferation has recently been suggested in nonrenal tissues. The aims of this study were to demonstrate that human proximal tubule cells (PTC) express functional PAR-2 and to investigate whether its activation can mediate proinflammatory and proliferative responses in these cells. Primary human PTC were cultured under serum-free conditions with or without the PAR-2-activating peptide SLIGKV-NH2(up to 800 μM), a control peptide, VKGILS-NH2(200 μM), or trypsin (0.01–100 nM). PAR-2 expression (RT-PCR), intracellular Ca2+mobilization (fura-2 fluorimetry), DNA synthesis (thymidine incorporation), fibronectin production (ELISA, Western blotting), and monocyte chemotactic protein (MCP)-1 secretion (ELISA) were measured. Trypsinogen expression in kidney and PTC cultures was determined by immunohistochemistry and Western blotting. In the kidney PTC were the predominant cell type expressing PAR-2. SLIGKV-NH2, but not VKGILS-NH2, stimulated a rapid concentration-dependent mobilization of intracellular Ca2+and ERK1/2 phosphorylation and, by 24 h, increases in DNA synthesis, fibronectin secretion, and MCP-1 secretion. These delayed responses appeared to be independent of ERK1/2. Trypsin produced similar rapid but not delayed responses. Trypsinogen was weakly expressed by PTC in the kidney and in culture. In summary, PTC are the main site of PAR-2 expression in the human kidney. In PTC cultures SLIGKV-NH2initiates proinflammatory and proliferative responses. Trypsinogen expressed within the kidney has the potential to contribute to PAR-2 activation in certain circumstances.
Control of Sensorimotor Variability by Consequences
Authors: Madelain Laurent , Champrenaut Lucie , Chauvin Alan
Published: August 2007

Studies of reaction-time distributions provide a useful quantitative approach to understand decision processes at the neural level and at the behavioral level. A strong relationship between the spread of latencies and the median is generally accepted even though there has been no attempt to disentangle experimentally these two parameters. Here we test the ability to independently control the median and the variability in reaction times. Reaction times were measured in human subjects instructed to make a discrimination between a target and a distractor in a 2AFC task. In a first experiment, saccadic latencies were measured. In a second experiment, we used manual response reaction times. Subjects were trained to produce four different reaction-time distributions. A reinforcing feedback was given depending on both the variability and the median of the latency distributions. When low variability was reinforced, the standard deviation (SD) of reaction-time distributions were reduced by a factor of two and when high variability was reinforced, the SD returned to baseline level. Our procedure independently affected the spread and the median of the distribution patterns. By fitting the latency distributions using the Reddi and Carpenter LATER model, we found that these effects could be simulated by changing the distribution of the noise affecting the decision process. Our results demonstrate that learned contingencies can affect reaction time variability and support the view that the so-called noise level in decision processes can undergo long-term changes.
Simultaneous Detection of Climate Change and Observing Biases in a Network with Incomplete Sampling
Authors: Sherwood Steven C.
Published: August 2007

All instrumental climate records are affected by instrumentation changes and variations in sampling over time. While much attention has been paid to the problem of detecting “change points” in time series, little has been paid to the statistical properties of climate signals that result after adjusting (“homogenizing”) the data—or to the effects of the irregular sampling and serial correlation exhibited by real climate records. These issues were examined here by simulating multistation datasets. Simple homogenization methods, which remove apparent artifacts and then calculate trends, tended to remove some of the real signal. That problem became severe when change-point times were not known a priori, leading to significant underestimation of real and/or artificial trends. A key cause is false detection of change points, even with nominally strict significance testing, due to serial correlation in the data. One conclusion is that trends in previously homogenized radiosonde datasets should be viewed with caution.

Two-phase regression reduced but did not resolve this problem. A new approach is proposed in which trends, change points, and natural variability are estimated simultaneously. This is accomplished here for the case of incomplete data from a fixed station network by an adaptation of the “iterative universal Kriging” method, which converges to maximum-likelihood parameters by iterative imputation of missing values. With careful implementation this method’s trend estimates had low random errors and were nearly unbiased in these tests. It is argued that error-free detection of change points is neither realistic nor necessary, and that success should be measured instead by the integrity of climate signals.
Midsummer Gap Winds and Low-Level Circulation over the Eastern Tropical Pacific
Authors: Romero-Centeno Rosario , Zavala-Hidalgo Jorge , Raga G. B.
Published: August 2007

The low-level seasonal and intraseasonal wind variability over the northeastern tropical Pacific (NETP), its relationship with other variables, and the connection with large- and middle-scale atmospheric patterns are analyzed using a suite of datasets. Quick Scatterometer (QuikSCAT) wind data show that the low-level circulation over the NETP is mainly affected by the northerly trades, the southerly trades, and the wind jets crossing through the Tehuantepec, Papagayo, and Panama mountain gaps. The seasonal and intraseasonal evolution of these wind systems determines the circulation patterns over the NETP, showing predominant easterly winds in winter and early spring and wind direction reversals in summer over the central region of the NETP. During summer, when southerly trades are the strongest and reach their maximum northward penetration, weak westerlies are observed in June, easterlies in July–August, despite that strong southerlies tend to turn eastward, and again westerlies in September–October. This circulation pattern appears to be related to the Tehuantepec and Papagayo jets, which slightly strengthen during midsummer favored by the westward elongation and intensification of the Azores–Bermuda high (ABH). This ABH evolution induces an across-gap pressure gradient over the Isthmus of Tehuantepec favoring the generation of the jet and a meridional sea level pressure (SLP) gradient in the western Caribbean that favors the funneling of the trade winds through the Papagayo gap. The SLP pattern causing the gap winds in winter is different than in midsummer, being the southeastward intrusion of high pressure systems coming from the northwest, the main cause of the large meridional SLP gradients in Tehuantepec and the western Caribbean.

The westward low-level circulation observed over the central-eastern region of the NETP during midsummer induces westward moisture fluxes in the lower layers of the atmosphere, displaces convergence areas away from the coasts, and confines the relatively strong convergence in the easternmost NETP to the south of the area of influence of the wind jets and associated easterlies, contributing to the development of the midsummer drought observed in southern Mexico and Central America.
Climate and Vegetation in the Middle East: Interannual Variability and Drought Feedbacks
Authors: Zaitchik Benjamin F. , Evans Jason P. , Geerken Roland A. , Smith Ronald B.
Published: August 2007

The Euphrates Plain (EP) experiences large interannual variability in vegetation cover, especially in areas of marginal rain-fed agriculture. Vegetation in this region is primarily limited by available soil moisture, as determined by winter precipitation, spring precipitation, and air temperature. Satellite analyses indicate that the springtime normalized difference vegetation index (NDVI) is negatively correlated with surface albedo, and that interannual variability in albedo in the EP produces an estimated forcing on the radiation balance that peaks at 16.0 W m−2 in May.

Simulations with a regional climate model indicate that surface energy fluxes during a drought year (1999) differed substantially from those during a year with normal precipitation (2003). These differences were geographically specific, with the EP exhibiting increased albedo and decreased sensible heat flux while the neighboring Zagros Plateau region showed no albedo effect, a large increase in sensible heat flux, and an offsetting reduction in latent heat flux. In both the EP and the Zagros there was a potential for positive feedbacks on temperature and drought in late spring, though the most likely feedback mechanisms differed between the two regions: in the EP surface brightening leads to cooling and reduced turbulent heat flux, while in the Zagros region reduced latent heat flux leads to warming and a deepening of the planetary boundary layer.
Coupling of Vegetation Growing Season Anomalies and Fire Activity with Hemispheric and Regional-Scale Climate Patterns in Central and East Siberia
Authors: Balzter Heiko , Gerard France , George Charles , Weedon Graham , Grey Will , Combal Bruno , Bartholomé Etienne , Bartalev Sergey , Los Sietse
Published: August 2007

An 18-yr time series of the fraction of absorbed photosynthetically active radiation (fAPAR) taken in by the green parts of vegetation data from the NOAA Advanced Very High Resolution Radiometer (AVHRR) instrument series was analyzed for interannual variations in the start, peak, end, and length of the season of vegetation photosynthetic activity in central and east Siberia. Variations in these indicators of seasonality can give important information on interactions between the biosphere and atmosphere. A second-order local moving window regression model called the “camelback method” was developed to determine the dates of phenological events at subcontinental scale. The algorithm was validated by comparing the estimated dates to phenological field observations. Using spatial correlations with temperature and precipitation data and climatic oscillation indices, two geographically distinct mechanisms in the system of climatic controls of the biosphere in Siberia are postulated: central Siberia is controlled by an “Arctic Oscillation–temperature mechanism,” while east Siberia is controlled by an “El Niño–precipitation mechanism.” While the analysis of data from 1982 to 1991 indicates a slight increase in the length of the growing season for some land-cover types due to an earlier beginning of the growing season, the overall trend from 1982 to 1999 is toward a slightly shorter season for some land-cover types caused by an earlier end of season. The Arctic Oscillation tended toward a more positive phase in the 1980s leading to enhanced high pressure system prevalence but toward a less positive phase in the 1990s. The results suggest that the two mechanisms also control the fire regimes in central and east Siberia. Several extreme fire years in central Siberia were associated with a highly positive Arctic Oscillation phase, while several years with high fire damage in east Siberia occurred in El Niño years. An analysis of remote sensing data of forest fire partially supports this hypothesis.