bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological profile of the novel mammalian tachykinin, hemokinin 1
Authors: Bellucci Francesca , Carini Francesca , Catalani Claudio , Cucchi Paola , Lecci Alessandro , Meini Stefania , Patacchini Riccardo , Quartara Laura , Ricci Renzo , Tramontana Manuela , Giuliani Sandro , Maggi Carlo Alberto
Published: June 2006

The effects of the novel mammalian tachykinin, hemokinin 1 (HEK‐1), have been investigated by radioligand binding and functional in vitro and in vivo experiments.

Similar to SP (Ki=0.13 nM), HEK‐1 inhibited in a concentration‐dependent manner and with high affinity [3H]‐substance P (SP) binding to human NK1 receptor (Ki=0.175 nM) while its affinity for [125I]‐neurokinin A (NKA) binding at human NK2 receptor was markedly lower (Ki=560 nM).

In isolated bioassays HEK‐1 was a full agonist at tachykinin NK1, NK2 and NK3 receptors. In the rat urinary bladder (RUB) HEK‐1 was about 3 fold less potent than SP. In the rabbit pulmonary artery (RPA) HEK‐1 and in the guinea‐pig ileum (GPI), HEK‐1 was about 500 fold less potent than NKA and NKB, respectively.

The responses to HEK‐1 were antagonized by GR 82334 in RUB (pKB=5.6±0.07), by nepadutant in RPA (pKB=8.6±0.04) and by SR 142801 in GPI (pKB=9.0±0.2) with apparent affinities comparable to that measured against tachykinin NK1, NK2 and NK3 receptor‐selective agonists, respectively.

Intravenous HEK‐1 produced dose‐related decrease of blood pressure in anaesthetized guinea‐pigs (ED50=0.1 nmol kg−1) and salivary secretion in anaesthetized rats (ED50=6 nmol kg−1) with potencies similar to that of SP. All these effects were blocked by the selective tachykinin NK1 receptor antagonist, SR 140333.

We conclude that HEK‐1 is a full agonist at tachykinin NK1, NK2 and NK3 receptors, possesses a remarkable selectivity for NK1 as compared to NK2 or NK3 receptors and acts in vivo experiments with potency similar to that of SP.

British Journal of Pharmacology (2002) 135, 266–274; doi:10.1038/sj.bjp.0704443
Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA‐, α1‐ and 5‐HT2A‐receptors
Authors: Sebban Claude , Tesolin‐Decros Brigitte , Ciprian‐Ollivier Jorge , Perret Laurent , Spedding Michael
Published: June 2006

The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0 – 30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1 – 3 mg kg−1s.c.) caused a marked dose‐dependent increase in EEG power in the frontal cortex at 1 – 3 Hz with decreases in power at higher frequencies (9 – 30 Hz). At high doses (3 mg kg−1s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05 – 0.1 mg kg−1i.p.) caused similar effects but with lesser changes in power.

In contrast, the non‐competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1 – 10 mg kg−1i.p.) The atypical antipsychotic clozapine (0.2 mg kg−1s.c.) synchronized the EEG (peak 8 Hz). The 5‐HT2A‐antagonist, M100907, specifically increased EEG power at 2 – 3 Hz at low doses (10 and 50 μg kg÷1s.c.), whereas at higher doses (0.1 mg kg−1s.c.) the profile resembled that of clozapine.

Clozapine (0.2 mg kg−1s.c.), GYKI 53655 (5 mg kg−1i.p.), prazosin (0.05 and 0.1 mg kg−1i.p.), and M100907 (0.01 and 0.05 mg kg−1s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg−1s.c.), but not the increase in power at 1 – 3 Hz in prefrontal cortex.

British Journal of Pharmacology(2002)135, 65–78; doi:10.1038/sj.bjp.0704451
Expression of mRNA and functional alpha1‐adrenoceptors that suppress the GIRK conductance in adult rat locus coeruleus neurons
Authors: Osborne Peregrine B , Vidovic Maria , Chieng Billy , Hill Caryl E , Christie MacDonald J
Published: June 2006

Locus coeruleus neurons in adult rats express binding sites and mRNA for α1‐adrenoceptors even though the depolarizing effect of α1‐adrenoceptor agonists on neonatal neurons disappears during development.

In this study intracellular microelectrodes were used to record from locus coeruleus neurons in brain slices of adult rats and reverse transcription‐polymerase chain reaction (RT – PCR) was used to investigate the mRNA expression of α1‐ and α2‐adrenoceptors in juvenile and adult rats.

The α1‐adrenoceptor agonist phenylephrine had no effect on the membrane conductance of locus coeruleus neurons (Vhold −60 mV) but decreased the G protein coupled, inward rectifier potassium (GIRK) conductance induced by α2‐adrenoceptor or μ‐opioid agonists. The GIRK conductance induced by noradrenaline was increased in amplitude when α1‐adrenoceptors were blocked with prazosin.

RT – PCR of total cellular RNA isolated from microdissected locus coeruleus tissue demonstrated strong mRNA expression of α1a‐, α1b‐ and α1d‐adrenoceptors in both juvenile and adult rats. However, only mRNA transcripts for the α1b‐adrenoceptors were consistently detected in cytoplasmic samples taken from single locus coeruleus neurons of juvenile rats, suggesting that this subtype may be responsible for the physiological effects seen in juvenile rats.

Juvenile and adult locus coeruleus tissue expressed mRNA for the α2a‐ and α2c‐adrenoceptors while the α2b‐adrenoceptor was only weakly expressed in juveniles and was not detected in adults.

The results of this study show that α1‐adrenoceptors expressed in adult locus coeruleus neurons function to suppress the GIRK conductance that is activated by μ‐opioid and α2‐adrenoceptors.

British Journal of Pharmacology (2002) 135, 226–232; doi:10.1038/sj.bjp.0704453
Capacitative Ca2+ entry in vascular endothelial cells is mediated via pathways sensitive to 2 aminoethoxydiphenyl borate and xestospongin C
Authors: Bishara Nour B , Murphy Timothy V , Hill Michael A
Published: June 2006

Agonists increase endothelial cell intracellular Ca2+, in part, by capacitative entry, which is triggered by the filling state of intracellular Ca2+ stores. It has been suggested that depletion of endoplasmic reticulum (ER) Ca2+ stores either leads to a physical coupling between the ER and a plasma membrane channel, or results in production of an intracellular messenger which affects the gating of membrane channels. As an axis involving the IP3 receptor has been implicated in a physical coupling mechanism the aim of this study was to examine the effects of the putative IP3 receptor antagonists/modulators, 2 aminoethoxydiphenyl borate (2APB) and xestospongin C, on endothelial cell Ca2+ entry.

Studies were conducted in fura 2 loaded cultured bovine aortic endothelial cells and endothelial cells isolated from rat heart.

2APB (30 – 300 μM) inhibited Ca2+ entry induced by both agonists (ATP 1 μM, bradykinin 0.1 μM) and receptor‐independent mechanisms (thapsigargin 1 μM, ionomycin 0.5 and 5 μM). 2APB did not diminish endothelial cell ATP‐induced production of IP3 nor effect in vitro binding of [3H]‐IP3 to an adrenal cortex binding protein. Capacitative Ca2+ entry was also blocked by disruption of the actin cytoskeleton with cytochalasin (100 nM) while the initial Ca2+ release phase was unaffected.

Similarly to 2APB, xestospongin C (3 – 10 μM) inhibited ATP‐induced Ca2+ release and capacitative Ca2+ entry. Further, xestospongin C inhibited capacitative Ca2+ entry induced by thapsigargin (1 μM) and ionomycin (0.5 μM).

The data are consistent with a mechanism of capacitative Ca2+ entry in vascular endothelial cells which requires (a) IP3 receptor binding and/or an event distal to the activation of the ER receptor and (b) a spatial relationship, dictated by the cytoskeleton, between Ca2+ release and entry pathways.

British Journal of Pharmacology (2002) 135, 119–128; doi:10.1038/sj.bjp.0704465
The developing relationship between receptor‐operated and store‐operated calcium channels in smooth muscle
Authors: McFadzean Ian , Gibson Alan
Published: June 2006

Contraction of smooth muscle is initiated, and to a lesser extent maintained, by a rise in the concentration of free calcium in the cell cytoplasm ([Ca2+]i). This activator calcium can originate from two intimately linked sources – the extracellular space and intracellular stores, most notably the sarcoplasmic reticulum. Smooth muscle contraction activated by excitatory neurotransmitters or hormones usually involves a combination of calcium release and calcium entry. The latter occurs through a variety of calcium permeable ion channels in the sarcolemma membrane. The best‐characterized calcium entry pathway utilizes voltage‐operated calcium channels (VOCCs). However, also present are several types of calcium‐permeable channels which are non‐voltage‐gated, including the so‐called receptor‐operated calcium channels (ROCCs), activated by agonists acting on a range of G‐protein‐coupled receptors, and store‐operated calcium channels (SOCCs), activated by depletion of the calcium stores within the sarcoplasmic reticulum. In this article we will review the electrophysiological, functional and pharmacological properties of ROCCs and SOCCs in smooth muscle and highlight emerging evidence that suggests that the two channel types may be closely related, being formed from proteins of the Transient Receptor Potential Channel (TRPC) family.

British Journal of Pharmacology(2002)135, 1–13; doi:10.1038/sj.bjp.0704468
Transcriptional stimulation of the human NHE3 promoter activity by PMA: PKC independence and involvement of the transcription factor EGR-1
Authors: Malakooti Jaleh , Sandoval Ricardo , Amin Md. Ruhul , Clark Jeremy , Dudeja Pradeep K. , Ramaswamy Krishnamurthy
Published: June 2006

NHE3 (Na+/H+ exchanger 3) is essential for Na+ absorption in the ileum and is expressed in a cell-specific manner in the apical membrane of the intestinal epithelial cells. In the present study, we report the stimulatory effect of PMA on the hNHE3 (human NHE3) transcription. Pretreatment with actinomycin D or cycloheximide blocked the up-regulation of the NHE3 mRNA by PMA, indicating that the increased level of NHE3 mRNA expression is regulated by transcriptional activation and is dependent on de novo protein synthesis. 5′-Deletion of the promoter region and transfection analysis in C2BBe1 cells revealed that the PMA effect is mediated through a GC-rich DNA region between nt −88 and −69. Gel mobility-shift assays demonstrated that in nuclear extracts from C2BBe1 cells grown under the basal growth conditions, Sp1 (stimulating protein-1) and Sp3 interact with this GC-rich DNA region, while, in PMA-treated nuclear extracts, PMA-induced EGR-1 (early growth response gene product 1) transcription factor binds to the same site. Binding of EGR-1 diminished the Sp1 and Sp3 interactions with this promoter region significantly. Co-transfection of Sp1 or Sp3 into SL2 cells activated the NHE3-reporter constructs, suggesting that Sp1 and Sp3 act as positive regulators of the NHE3 expression. In addition, overexpression of EGR-1 was sufficient to transactivate the NHE3-reporter gene activity, and knockdown of EGR-1 with gene-specific small interfering RNA resulted in inhibition of the PMA-induced up-regulation of the endogenous NHE3 mRNA expression. Furthermore, the PKC (protein kinase C) inhibitor chelerythrine chloride did not affect PMA-induced NHE3 promoter activity, suggesting that PMA stimulation of the hNHE3 gene expression may be PKC-independent.
Simplified modelling of metabolic pathways for flux prediction and optimization: lessons from an in vitro reconstruction of the upper part of glycolysis
Authors: Fiévet Julie B. , Dillmann Christine , Curien Gilles , de vienne Dominique
Published: June 2006

Explicit modelling of metabolic networks relies on well-known mathematical tools and specialized computer programs. However, identifying and estimating the values of the very numerous enzyme parameters inherent to the models remain a tedious and difficult task, and the rate equations of the reactions are usually not known in sufficient detail. A way to circumvent this problem is to use ‘non-mechanistic’ models, which may account for the behaviour of the systems with a limited number of parameters. Working on the first part of glycolysis reconstituted in vitro, we showed how to derive, from titration experiments, values of effective enzyme activity parameters that do not include explicitly any of the classical kinetic constants. With a maximum of only two parameters per enzyme, this approach produced very good estimates for the flux values, and enabled us to determine the optimization conditions of the system, i.e. to calculate the set of enzyme concentrations that maximizes the flux. This fast and easy method should be valuable in the context of integrative biology or for metabolic engineering, where the challenge is to deal with the dramatic increase in the number of parameters when the systems become complex.
Wild-type and mutant ferroportins do not form oligomers in transfected cells
Authors: Gonçalves Ana Sofia , Muzeau Françoise , Blaybel Rand , Hetet Gilles , Driss Fathi , Delaby Constance , Canonne-Hergaux François , Beaumont Carole
Published: June 2006

Ferroportin [FPN; Slc40a1 (solute carrier family 40, member 1)] is a transmembrane iron export protein expressed in macrophages and duodenal enterocytes. Heterozygous mutations in the FPN gene result in an autosomal dominant form of iron overload disorder, type-4 haemochromatosis. FPN mutants either have a normal iron export activity but have lost their ability to bind hepcidin, or are defective in their iron export function. The mutant protein has been suggested to act as a dominant negative over the wt (wild-type) protein by multimer formation. Using transiently transfected human epithelial cell lines expressing mouse FPN modified by the addition of a haemagglutinin or c-Myc epitope at the C-terminus, we show that the wtFPN is found at the plasma membrane and in Rab5-containing endosomes, as are the D157G and Q182H mutants. However, the delV162 mutant is mostly intracellular in HK2 cells (human kidney-2 cells) and partially addressed at the cell surface in HEK-293 cells (human embryonic kidney 293 cells). In both cell types, it is partially associated with the endoplasmic reticulum and with Rab5-positive vesicles. However, this mutant is complex-glycosylated like the wt protein. D157G and G323V mutants have a defective iron export capacity as judged by their inability to deplete the intracellular ferritin content, whereas Q182H and delV162 have normal iron export function and probably have lost their capacity to bind hepcidin. In co-transfection experiments, the delV162 mutant does not co-localize with the wtFPN, does not prevent its normal targeting to the plasma membrane and cannot be immunoprecipitated in the same complex, arguing against the formation of FPN hetero-oligomers.
Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism
Authors: Salvi Mauro , Battaglia Valentina , Mancon Mario , Colombatto Sebastiano , Cravanzola Carlo , Calheiros Rita , Marques Maria P. M. , Grillo Maria A. , Toninello Antonio
Published: June 2006

Agmatine, a divalent diamine with two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism the driving force of which is ΔΨ (electrical membrane potential). Although this process showed strict electrophoretic behaviour, qualitatively similar to that of polyamines, agmatine is most probably transported by a specific uniporter. Shared transport with polyamines by means of their transporter is excluded, as divalent putrescine and cadaverine are ineffective in inhibiting agmatine uptake. Indeed, the use of the electroneutral transporter of basic amino acids can also be discarded as ornithine, arginine and lysine are completely ineffective at inducing the inhibition of agmatine uptake. The involvement of the monoamine transporter or the existence of a leak pathway are also unlikely. Flux-voltage analysis and the determination of activation enthalpy, which is dependent upon the valence of agmatine, are consistent with the hypothesis that the mitochondrial agmatine transporter is a channel or a single-binding centre-gated pore. The transport of agmatine was non-competitively inhibited by propargylamines, in particular clorgilyne, that are known to be inhibitors of MAO (monoamine oxidase). However, agmatine is normally transported in mitoplasts, thus excluding the involvement of MAO in this process. The I2 imidazoline receptor, which binds agmatine to the mitochondrial membrane, can also be excluded as a possible transporter since its inhibitor, idazoxan, was ineffective at inducing the inhibition of agmatine uptake. Scatchard analysis of membrane binding revealed two types of binding site, S1 and S2, both with mono-co-ordination, and exhibiting high-capacity and low-affinity binding for agmatine compared with polyamines.

Agmatine transport in liver mitochondria may be of physiological importance as an indirect regulatory system of cytochrome c oxidase activity and as an inducer mechanism of mitochondrial-mediated apoptosis.
Regulation of prokaryotic adenylyl cyclases by CO2
Authors: Hammer Arne , Hodgson David R. W. , Cann Martin J.
Published: June 2006

The Slr1991 adenylyl cyclase of the model prokaroyte Synechocystis PCC 6803 was stimulated 2-fold at 20 mM total Ci (inorganic carbon) at pH 7.5 through an increase in kcat. A dose response demonstrated an EC50 of 52.7 mM total Ci at pH 6.5. Slr1991 adenylyl cyclase was activated by CO2, but not by HCO3−. CO2 regulation of adenylyl cyclase was conserved in the CyaB1 adenylyl cyclase of Anabaena PCC 7120. These adenylyl cyclases represent the only identified signalling enzymes directly activated by CO2. The findings prompt an urgent reassessment of the activating carbon species for proposed HCO3−-activated adenylyl cyclases.
Cleavage, a real turn-off? HIV-mediated proteolysis of PABP1
Authors: Collier Brian , Gray Nicola K.
Published: June 2006

In this issue of the Biochemical Journal, Álvarez and colleagues have identified PABP1 [poly(A)-binding protein 1] as a target of protease cleavage during HIV infection. The study shows that HIV-1, HIV-2 and mouse mammary tumour virus, but not other retroviruses, target PABP1 for cleavage and identifies cleavage sites within the RNA-recognition motifs and C-terminal region of the protein. This suggests that PABP1 cleavage may be important in the shut-off of host translation during HIV infection. This extends the viral families that are known to target PABP1 to include Retroviridae, suggesting that PABP1 may be a central target of viral infection.
Reducing or eliminating the dry period of dairy cows
Authors: Stockdale C. R.
Published: June 2006

This review considers the research that has been conducted recently on reducing the length of the dry period of dairy cows, with particular emphasis on the effects of eliminating the dry period altogether. Milk yield in the subsequent lactation is reduced by up to 25%, but this loss is offset to some degree by the milk produced when cows would otherwise be dry. The lower subsequent milk yield in cows continuously milked is most likely to be a consequence of changes in the mammary gland during late gestation rather than insufficient feed or body condition to maintain milk synthesis. Shortening or eliminating the dry period may result in a lower incidence of metabolic problems post-partum, and a reduced negative energy balance in early lactation due to the maintenance of dietary intake while milk yields and body condition loss are reduced. The reductions in both body condition loss and negative energy balance may have a beneficial influence on reproductive performance. However, it is concluded that more research, particularly with cows that graze pasture during lactation, together with an economic appraisal, is needed before it could be recommended that Australian dairy farmers change their current dry period practices, particularly if continuous milking was to be considered.
Using machine vision classification to control access of animals to water
Authors: Finch N. A. , Murray P. J. , Dunn M. T. , Billingsley J.
Published: June 2006

Invasive vertebrate pests together with overabundant native species cause significant economic and environmental damage in the Australian rangelands. Access to artificial watering points, created for the pastoral industry, has been a major factor in the spread and survival of these pests. Existing methods of controlling watering points are mechanical and cannot discriminate between target species. This paper describes an intelligent system of controlling watering points based on machine vision technology. Initial test results clearly demonstrate proof of concept for machine vision in this application. These initial experiments were carried out as part of a 3-year project using machine vision software to manage all large vertebrates in the Australian rangelands. Concurrent work is testing the use of automated gates and innovative laneway and enclosure design. The system will have application in any habitat throughout the world where a resource is limited and can be enclosed for the management of livestock or wildlife.
Profitable feeding of dairy cows on irrigated dairy farms in northern Victoria
Authors: Wales W. J. , Heard J. W. , Ho C. K. M. , Leddin C. M. , Stockdale C. R. , Walker G. P. , Doyle P. T.
Published: June 2006

Milk production per cow and per farm in the irrigated region in northern Victoria have increased dramatically over the past 2 decades. However, these increases have involved large increases in inputs, and average productivity gains on farms have been modest. Before the early 1980s, cows were fed predominantly pasture and conserved fodder. There is now large diversity in feeding systems and feed costs comprise 40–65% of total costs on irrigated dairy farms. This diversity in feeding systems has increased the need to understand the nutrient requirements of dairy cows and the unique aspects of nutrient intake and digestion in cows at grazing. Principles of nutrient intake and supply to the grazing dairy cow from the past 15 years’ research in northern Victoria are summarised and gaps in knowledge for making future productivity gains are identified. Moreover, since the majority of the milk produced in south-eastern Australia is used in the manufacture of products for export, dairy companies have increased their interest in value-added dairy products that better meet nutritional requirements or provide health benefits for humans. Finally, some examples of the impacts of farm system changes on operating profit for some case study farms in northern Victoria are presented to illustrate the need for thorough analysis of such management decisions.
Prenatal programming of postnatal productivity and health of livestock: a brief review
Authors: Bell A. W.
Published: June 2006

Human epidemiological evidence has suggested that metabolic perturbations during fetal life may increase predisposition to cardiovascular disease, type 2 diabetes and obesity in later life. A growing number of controlled experiments on sheep and other large animal species are adding to the already large body of experimental evidence from rat studies in supporting the ‘fetal origins’ hypothesis. Of particular practical relevance are findings that maternal undernutrition in late pregnancy can predispose lambs to glucose intolerance and increased adiposity in early adulthood. This effect may be exacerbated by high energy intakes and limited capacity for muscle growth in undernourished or growth-retarded lambs during early postnatal life. Recent Australian studies have demonstrated the effects of prenatal nutrition on postnatal growth and meat production in beef cattle, and on quantity and quality of wool production in sheep.
Converting IL-15 to a superagonist by binding to soluble IL-15Rα
Authors: Rubinstein Mark P. , Kovar Marek , Purton Jared F. , Cho Jae-Ho , Boyman Onur , Surh Charles D. , Sprent Jonathan
Published: June 2006

IL-15 is normally presentedin vivoas a cell-associated cytokine bound to IL-15Rα. We show here that the biological activity of soluble IL-15 is much improved after interaction with recombinant soluble IL-15Rα; after injection, soluble IL-15/IL-15Rα complexes rapidly induce strong and selective expansion of memory-phenotype CD8+cells and natural killer cells. These findings imply that binding of IL-15Rα to IL-15 may create a conformational change that potentiates IL-15 recognition by the βγcreceptor on T cells. The enhancing effect of IL-15Rα binding may explain why IL-15 normally functions as a cell-associated cytokine. Significantly, the results with IL-2, a soluble cytokine, are quite different; thus, IL-2 function is markedly inhibited by binding to soluble IL-2Rα.
Timing and rate of speciation inAgave(Agavaceae)
Authors: Good-Avila Sara V. , Souza Valeria , Gaut Brandon S. , Eguiarte Luis E.
Published: June 2006

TheAgave(Agavaceae) are keystone species of semiarid to arid regions where the geographic center of origin is Mexico but whose populations spread from the southwestern U.S. through Central America, the Caribbean, and into northern South America. Our analyses indicate thatAgaveis a young genus, between 7.8 and 10.1 million years old, and yet it harbors the most species of any genera in the family. Of the eight genera in the family,Agaveis paraphyletic with respect to three of them, and these four genera are often grouped into a genus termedAgave sensu lato, which harbors 208 of the 293 recognized species in the Agavaceae. In this article, we examine the phylogenetic limits ofAgave sensu latoand present analyses elucidating the origin and rate of speciation in the group. These analyses lead to some new insights into the phylogenetic limits ofAgave, indicate an estimated age of the family between 20 and 26 million years and an age of theAgave sensu latoof ≤10 million years. Furthermore, we estimate a high mean per-lineage rate of diversification for the genus and find that rates of speciation were significantly elevated between 8 and 6 million years ago and then again between 3 and 2.5 million years ago. We discuss the potential for both monocarpy and the evolution of a generalist pollination system, largely dependent on nectarivorous bat species, as possible driving factors in the radiation of the group.
Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees
Authors: Zhang Pei , Yu Mei-ying W. , Venable Richard , Alter Harvey J. , Shih J. Wai-Kou
Published: June 2006

Neutralizing monoclonal antibody (BX-182) directed against theddeterminant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtypeadwbut not by subtypeayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present inadsubtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority ofaysubtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype “d” epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants.
Digestive and metabolic effects of altering feeding frequency in athletic horses
Authors: Jansson A , Sandin A , Lindberg JE
Published: June 2006

The aim of this study was to investigate the effect of feeding frequency on total tract digestibility and plasma glucose, insulin, urea, gastrin and cortisol concentrations at rest and following exercise in seven Standardbred horses in race training. The horses were fed every 12 h (twice a day, 2TD) and every 4 h (six times a day, 6TD) for 25 days, in a cross-over design. The diet (64% grass hay, 36% concentrates on weight basis) was fed at twice the maintenance energy requirement. Blood samples were taken every hour for 24 h on day 17, total collection of urine and faeces was made on days 19–21 and an intensive exercise test was performed on day 25. Altering feeding frequency caused small variations in diurnal plasma glucose, urea, gastrin and cortisol concentrations and did not affect total tract nutrient digestibility. There was an increase in the mean diurnal plasma urea concentration on the 2TD regime and low levels of plasma insulin were observed 7 h after feeding 2TD. The response to intensive exercise on heart rate, plasma lactate and plasma glucose was similar on both treatments but the plasma insulin concentration was higher following exercise in the 2TD regime, indicating that post-exercise glucose metabolism was altered. In conclusion, this study shows that feeding athletic horses only 2TD caused metabolic signs resembling those observed during feed deprivation (low levels of plasma insulin and an increased diurnal plasma urea concentration) and an altered post-exercise glucose metabolism, but did not affect the digestive response.
The freestyle dressage competition as a test of the horse's performance
Authors: Stachurska A , Pięta M , Niewczas J , Markowski W
Published: June 2006

The objective of the study has been to examine whether the freestyle dressage classes are judged reliably and to elaborate a method assessing the consistency of judging. The data contained 13 000 marks of the ten best-ranked horses at nine Grand Prix classes and four Intermediate I classes from ten international competitions. The marks concerned 119 horses in total and were given by 37 judges. A method for evaluating the consistency of judging has been proposed. The index of disagreement (ID) assesses the disagreement of ranking by an individual judge relative to the general ranking based on the sum of marks awarded by five judges. The results show that the mean ID of individual judges is highly differentiated. The ID is influenced by the judge's position in the arena. The consistency of judging was lower in Intermediate I Freestyle Tests than in Grand Prix Freestyle Tests and it varied in different competitions. The conclusion of the study is that the results of the freestyle dressage classes are often biased. The present system of judging should be permanently checked. The offered method of evaluating agreement between judges' rankings may help to improve the consistency of judging and the reliability of the horses' scores.
Risk Factors for Nosocomial Primary Bloodstream Infection in Pediatric Intensive Care Unit Patients: A 2-Year Prospective Cohort Study
Authors: Elward Alexis M. , Fraser Victoria J.
Published: June 2006

Objective.

The primary objective was to determine the rate of and risk factors for nosocomial primary bloodstream infection (BSI) in pediatric intensive care unit (PICU) patients in order to determine the validity of our previously published findings. The secondary objective was to analyze whether risk factors for primary BSI differed by organism type, particularly whether device use was more strongly associated with BSI due to gram-positive organisms.

Design.

Prospective cohort study.

Settings.

St. Louis Children's Hospital, a 235-bed academic tertiary care center with a 28-bed combined medical and surgical PICU.

Patients.

PICU patients admitted between September 1, 1999, and September 1, 2001.

Outcome Measures.

Nosocomial primary BSIs.

Results.

Of 2,310 patients, 55% were male, and 73% were white. There were 124 episodes of primary BSI in 87 patients (3.8%). Coagulase-negative Staphylococcus organisms were the leading cause of BSI (42 of 124 episodes). The rate of BSI was 9 BSIs/1,000 central venous catheter–days. Multiple logistic regression analysis showed that independent predictors of nosocomial primary BSI included higher number of arterial catheter–days (adjusted odds ratio [aOR], 5.7 per day of arterial catheterization; 95% confidence interval [CI], 3.4-9.8), higher number of packed red blood cell transfusions (aOR, 1.2; 95% CI, 1.1-1.4), and genetic syndrome (aOR, 4.7; 95% CI, 1.8-12). Severity of illness, underlying illnesses, and medications were not independently associated with increased risk of nosocomial BSI.

Conclusion.

Arterial catheter use and packed red blood cell transfusion are potentially modifiable risk factors for nosocomial primary BSI in PICU patients. Genetic syndromes may be markers for unrecognized immune defects that impair host defense against microorganisms.
Father-to-Infant Transmission of Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit
Authors: Al-Tawfiq Jaffar A.
Published: June 2006

Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly being recognized as a cause of community-acquired infection. Its transmission in neonatal intensive care units (NICUs) has reportedly been linked to a few cases of community-acquired MRSA (CA-MRSA) infection. Here, I describe a case of CA-MRSA transmission from a father to his child in a NICU. Recognition that CA-MRSA may be transmitted in a hospital setting raises important issues for MRSA infection control and treatment options.
Outbreak of Pertussis Among Healthcare Workers in a Hospital Surgical Unit
Authors: Pascual F. Brian , McCall Candace L. , McMurtray Aaron , Payton Tony , Smith Forrest , Bisgard Kristine M.
Published: June 2006

Background.

In September 1999, a pertussis outbreak was detected among surgical staff of a 138-bed community hospital. Patients were exposed toBordetella pertussisduring the 3-month outbreak period.

Objective.

To describe the outbreak among surgical staff, to evaluate implemented control measures, and to determine whether nosocomial transmission occurred.

Methods.

Clinical pertussis was defined as acute cough illness with a duration of 14 days or more without another apparent cause; persons with positive culture, PCR, or serologic test results were defined as having laboratory-confirmed pertussis. Surgical healthcare workers (HCWs) were interviewed regarding pertussis symptoms, and specimens were obtained for laboratory analysis. Patients exposed toB. pertussisduring an ill staff member's 3-week infectious period were interviewed by phone to determine the extent of nosocomial spread.

Participants.

A total of 53 HCWs assigned to the surgical unit and 146 exposed patients. HCWs with pertussis were defined as case subjects; HCWs without pertussis were defined as non-case subjects.

Results.

Twelve (23%) of 53 HCWs had clinical pertussis; 6 cases were laboratory confirmed. The median cough duration in the 12 case subjects was 27 days (range, 20-120 days); 10 (83%) had paroxysms. Eleven (92%) of 12 case subjects and 28 (86%) of 41 non-case subjects received antibiotic treatment or prophylaxis. Seven case subjects (58%) reported they always wore a mask when near patients. Of 146 patients potentially exposed to pertussis from the 12 case subjects, 120 (82%) were interviewed; none reported a pertussis-like illness.

Conclusions.

Surgical staff transmittedB. pertussisamong themselves; self-reported data suggests that these HCWs did not transmitB. pertussisto their patients, likely because of mask use, cough etiquette, and limited face-to-face contact. Control measures might have helped limit the outbreak once pertussis was recognized.
Analyzing Oppression
Authors: Cudd Ann E.
Published: June 2006

This book presents a new, integrated theory of social oppression, which tackles the fundamental question that no theory of oppression has satisfactorily answered: if there is no natural hierarchy among humans, why are some cases of oppression so persistent? The book argues that the explanation lies in the coercive co-opting of the oppressed to join in their own oppression. This answer sets the stage for analysis throughout the book, as it explores the questions of how and why the oppressed join in their oppression. The book argues that oppression is an institutionally structured harm perpetrated on social groups by other groups using direct and indirect material, economic, and psychological force. Among the most important and insidious of the indirect forces is an economic force that operates through oppressed persons' own rational choices. This force constitutes the central feature of analysis, and the book argues that this force is especially insidious because it conceals the fact of oppression from the oppressed and from others who would be sympathetic to their plight. The oppressed come to believe that they suffer personal failings and this belief appears to absolve society from responsibility. While in the book's view oppression is grounded in material exploitation and physical deprivation, it cannot be long sustained without corresponding psychological forces. The book examines the direct and indirect psychological forces that generate and sustain oppression. It discusses strategies that groups have used to resist oppression and argues that all persons have a moral responsibility to resist in some way. The concluding chapter proposes a concept of freedom that would be possible for humans in a world that is actively opposing oppression, arguing that freedom for each individual is only possible when we achieve freedom for all others.
Social Groups and Institutional Constraints
Authors: Cudd Ann E.
Published: June 2006

This chapter characterizes social groups and institutions in a way that meets the plausible objections of individualists, yet allows a social explanation of oppression. Topics discussed include explaining human behavior, social groups, institutionally structured constraints, oppression and social groups, social groups and group harm. It is argued that any account of oppression that distinguishes it from other types of harm that can come to individuals and locates it as a social injustice requires an account of social groups. Further, harms that accrue to members of voluntary and nonvoluntary groups must be treated separately in moral arguments.
Psychological Mechanisms of Oppression
Authors: Cudd Ann E.
Published: June 2006

This chapter is concerned with explaining how our cognitive psychology equips us for oppression, that is, what psychological mechanisms we have that allow and motivate us to oppress or suffer oppression. It addresses the question: what psychological mechanisms account for our tendency to form social groups and to invidiously discriminate among those groups? It argues that there are two main types of material forces of oppression — violence and economic deprivation — and that oppression cannot survive without being enforced by at least one of these material ways of harming persons. Violence is separated from economic deprivation to illustrate how different cases of oppression involve different kinds of reinforcements and argue that they will require different strategies of resistance.
Economic Forces of Oppression
Authors: Cudd Ann E.
Published: June 2006

This chapter discusses three main forces of economic oppression: oppressive economic systems (capitalism and socialism), direct forces of economic oppression, and indirect forces of economic oppression. It is argued that while capitalism and socialism are not intrinsically oppressive, both systems lend themselves to oppression in characteristic ways, and therefore each sort of system must take certain steps to guard against their respective characteristic oppressions. Direct forces of economic oppression are restrictions on opportunities that are applied from the outside on the oppressed, including enslavement, segregation, employment discrimination, group-based harassment, opportunity inequality, neocolonialism, and governmental corruption. Direct forces may not always be clearly visible, either because they happen far from the reach of legal authorities or from the view of consumers, or because they are diffused in a large society, and only apparent from a statistical analysis and comparison among social groups. In indirect forces, or oppression by choice, the oppressed are co-opted into making individual choices that add to their own oppression. When this force is at work the oppressed are faced with options that rationally induce them to choose against the collective good of their social group, and in the long run, against their own good as well. But choosing otherwise requires choosing against their own immediate interests, and changing their beliefs or preferences in ways that they may resent.
Psychological Harms of Oppression
Authors: Cudd Ann E.
Published: June 2006

This chapter discusses the direct and indirect psychological harms of oppression. Direct psychological harms are intentionally inflicted by dominant on subordinate groups. These include terror and psychological trauma, humiliation and degradation, objectification, religion, ideology, and cultural domination. Indirect psychological harms occur when the beliefs and values of the privileged or oppressor groups are subconsciously accepted by the subordinate and assimilated into their self-concept or value/belief scheme. Indirect forces thus work through the psychology of the oppressed to mold them and co-opt them to result in choices and decisions that harm the oppressed while benefiting the privileged. These include shame and low self-esteem, false consciousness, and deformed desire.
White spot syndrome virus VP24 interacts with VP28 and is involved in virus infection
Authors: Xie Xixian , Yang Feng
Published: June 2006

White spot syndrome virus(WSSV) is one of the most virulent pathogens causing high mortality in shrimp. Herein, the characterization of VP24, a major structural protein of WSSV, is described. When purified virions were subjected to Nonidet P-40 treatment to separate the envelopes from the nucleocapsids, VP24 was found to be present exclusively in the envelope fraction. Triton X-114 extraction also indicated that VP24 behaves as an envelope protein. Immunoelectron microscopy further confirmed that VP24 is located in the virion envelope. Far-Western experiments showed that VP24 interacts with VP28, another major envelope protein of the WSSV virion. To investigate the function of VP24, WSSV was neutralized with various amounts of anti-VP24 IgG and injected into crayfish. The results showed that anti-VP24 IgG could partially attenuate infection with WSSV. It is concluded that VP24 is an envelope protein and functions at an early stage in virus infection.
Phylogeography of the deer mouse (Peromyscus maniculatus) provides a predictive framework for research on hantaviruses
Authors: Dragoo Jerry W. , Lackey J. Alden , Moore Kathryn E. , Lessa Enrique P. , Cook Joseph A. , Yates Terry L.
Published: June 2006

Phylogeographical partitioning of Sin Nombre and Monongahela viruses (hantaviruses) may reflect that of their primary rodent host, the deer mouse (Peromyscus maniculatus). Lack of a comprehensive assessment of phylogeographical variation of the host has precluded the possibility of predicting spatial limits of existing strains of these viruses or geographical regions where novel viral strains might emerge. The complete cytochromebgene was sequenced for 206 deer mice collected from sites throughout North America to provide a foundation for future studies of spatial structure and evolution of this ubiquitous host. Bayesian analyses of these sequences partitioned deer mice into six largely allopatric lineages, some of which may represent unrecognized species. The geographical distributions of these lineages were probably shaped by Quaternary climatic events. Populations of mice were apparently restricted to refugia during glacial advances, where they experienced genetic divergence. Expansion of these populations, following climatic amelioration, brought genetically distinctive forms into contact. Occurrence of parallel changes in virus strains can now be explored in appropriate regions. In New Mexico, for example, near the location whereSin Nombre viruswas first discovered, there are three genetically distinctive lineages of deer mice whose geographical ranges need to be delineated precisely. The phylogeography ofP. maniculatusprovides a framework for interpreting geographical variability, not only in hosts, but also in associated viral variants and disease transmission, and an opportunity to predict the potential geographical distribution of newly emerging viral strains.
Prion protein polymorphisms in white-tailed deer influence susceptibility to chronic wasting disease
Authors: Johnson Chad , Johnson Jody , Vanderloo Joshua P. , Keane Delwyn , Aiken Judd M. , McKenzie Debbie
Published: June 2006

The primary sequence of the prion protein affects susceptibility to transmissible spongiform encephalopathies, or prion diseases, in mice, sheep and humans. The Prnp gene sequence of free-ranging, Wisconsin white-tailed deer was determined and the Prnp genotypes of chronic wasting disease (CWD)-positive and CWD-negative deer were compared. Six amino acid changes were identified, two of which were located in pseudogenes. Two alleles, a Q→K polymorphism at codon 226 and a single octapeptide repeat insertion into the pseudogene, have not been reported previously. The predominant alleles – wild-type (Q95, G96 and Q226) and a G96S polymorphism – comprised almost 98 % of the Prnp alleles in the Wisconsin white-tailed deer population. Comparison of the allelic frequencies in the CWD-positive and CWD-negative deer suggested that G96S and a Q95H polymorphism were linked to a reduced susceptibility to CWD. The G96S allele did not, however, provide complete resistance, as a CWD-positive G96S/G96S deer was identified. The G96S allele was also linked to slower progression of the disease in CWD-positive deer based on the deposition of PrPCWD in the obex region of the medulla oblongata. Although the reduced susceptibility of deer with at least one copy of the Q95H or G96S allele is insufficient to serve as a genetic barrier, the presence of these alleles may modulate the impact of CWD on white-tailed deer populations.
Sequence analysis of the fusion protein gene from infectious salmon anemia virus isolates: evidence of recombination and reassortment
Authors: Devold M. , Karlsen M. , Nylund A.
Published: June 2006

Studies of infectious salmon anemia virus (ISAV; genus Isavirus, family Orthomyxoviridae) haemagglutinin–esterase (HE) gene sequences have shown that this gene provides a tool for genotyping and, hence, a tool to follow the dissemination of ISAV. The problem with using only the HE gene is that ISAV has a segmented genome and one segment may not tell the whole story about the origin and history of ISAV from outbreaks. To achieve a better genotyping system, the present study has focused on segment 5, the fusion (F) protein gene, which contains sequence variation at about the same level as the HE gene. The substitution rates of the HE and F gene sequences, based on 54 Norwegian ISAV isolates, are 6.1(±0.3)×10−6 and 8.6(±5.0)×10−5 nt per site per year, respectively. The results of phylogenetic analysis of the two gene segments have been compared and, with the exception of a few cases of reassortment, they tell the same story about the ISAV isolates. A combination of the two segments is recommended as a tool for future genotyping of ISAV. Inserts (INs) of 8–11 aa may occur close to the cleavage site of the precursor F0 protein in some ISAV isolates. The nucleotide sequence of two of these INs shows 100 % sequence identity to parts of the 5′ end of the F protein gene, whilst the third IN is identical to a part of the nucleoprotein gene. This shows that recombination is one of the evolutionary mechanisms shaping the genome of ISAV. The possible importance of the INs with respect to virulence remains uncertain.