bluuebunny/crossref_metadata_2025 huggingface dataset:
Kingstonite, (Rh,Ir,Pt)3S4, a new mineral species from Yubdo, Ethiopia
Authors: Stanley C. J. , Criddle A. J. , Spratt J. , Roberts A. C. , Szymański J. T. , Welch M. D.
Published: September 2005

Kingstonite, ideally Rh3S4, is a new mineral from the Bir Bir river, Yubdo District, Wallaga Province, Ethiopia. It occurs as subhedral, tabular elongate to anhedral inclusions in a Pt-Fe nugget with the associated minerals isoferroplatinum, tetraferroplatinum, a Cu-bearing Pt-Fe alloy, osmium, enriched oxide remnants of osmium, laurite, bowieite, ferrorhodsite and cuprorhodsite. It is opaque with a metallic lustre, has a black streak, is brittle and has a subconchoidal fracture and a good cleavage parallel to [001]. VHN25 is 871–920 kg/mm2. In plane-polarized reflected light, kingstonite is a pale slightly brownish grey colour. It is weakly pleochroic and displays a weak bireflectance. It does not possess internal reflections. The anisotropy is weak to moderate in dull greys and browns. Reflectance data and colour values are tabulated. Average results of twenty electron microprobe analyses on four grains give Rh 46.5, Ir 16.4, Pt 11.2, S 25.6, total 99.7 wt.%. The empirical formula is (Rh2.27Ir0.43Pt0.29)Σ2.99S4.01, based on 7 atoms per formula unit (a.p.f.u.). Kingstonite is monoclinic (C2/m) with a = 10.4616(5), b = 10.7527(5), c = 6.2648(3) Å, β = 109.000(5)°, V = 666.34(1) Å3 (Z = 6). The calculated density is 7.52 g/cm3 (on the basis of the empirical formula and unit-cell parameters refined from powder data). The seven strongest X-ray powder-diffraction lines [d in Å(I) (hkl)] are: 3.156 (100) (310), 3.081 (100) (31), 2.957 (90) (002), 2.234 (60) (202), 1.941 (50) (23), 1.871 (80) (41) and 1.791 (90) (060, 33). The structure of kingstonite was solved and refined to Rp = 3.8%. There are four distinct metal sites with Rh occupancies of 0.64–0.89. Two metal sites are regular RhS6 octahedra that share edges to form a ribbon running parallel to c. The other two metal sites are coordinated by 4 S + 2 Rh and 5 S + 2 Rh and define a puckered Rh6 ring. The ribbons of regular RhS6 octahedra alternate with the columns of Rh6 rings linked by S atoms. S–S bridges also connect the ribbons and columns. As such, the kingstonite structure is essentially that of synthetic Rh3S4. Minor differences in the unit-cell parameters, atom coordinates and displacement parameters of kingstonite and synthetic Rh3S4 arise from the considerable substitution of Ir for Rh. The mineral name honours Gordon Kingston (formerly of Cardiff University) in recognition of his contributions to platinum group element mineralogy and the geology of their mineral deposits.
Mechanical graphite transport in fault zones and the formation of graphite veins
Authors: Crespo E. , Luque J. , Barrenechea J. F. , Rodas M.
Published: September 2005

This paper describes a vein-shaped graphite occurrence in which, for the first time, the geological, mineralogical and isotopic evidence support its formation by physical remobilization of previously formed syngenetic graphite. The deposit studied is located in the Spanish Central System and it occurs along the contact between a hydrothermal Ag-bearing quartz vein and a graphite-bearing quartzite layer. The characteristics of this occurrence differ from those of fluid-deposited vein-type graphite mineralization in that: (1) graphite flakes are oriented parallel to the vein walls; (2) graphite crystallinity is slightly lower than in the syngenetic precursor (graphite disseminated in the quartzite); and (3) the isotopic signatures of both types of graphite are identical and correspond to biogenic carbon. In addition, theP-Tconditions of the hydrothermal Ag-bearing quartz veins in the study area (P<1 kbar, andTup to 360°C) contrast with the high degree of structural order of graphite in the vein. Therefore, physical remobilization of graphite can be regarded as a suitable alternative mechanism to account for some cases of vein-shaped graphite deposits. Such a mechanism would require a previous concentration of disseminated syngenetic graphite promoted, in this case, by the retrograde solubility of quartz. This process would generate monomineralic graphite aggregates enhancing its lubricant properties and permitting graphite to move in the solid state along distances in the range of up to several metres.
Contrasting Fe-Ca distributions and related microtextures in syenite alkali feldspar from the Patagonian Andes, Chile
Authors: Nakano Satoshi , Akai J. , Shimobayashi N.
Published: September 2005

Contrasting distribution patterns of Fe and Ca have been found by electron microprobe analysis (EMPA) mapping of alkali feldspar in a quartz syenite from the Patagonian Andes, Chile. They comprise mainly mantle zoning (Fe-rich, Ca-poor rims and Fe-poor, Ca-rich interiors) and corresponding patchy zoning in grain interiors. The rims are dominantly of turbid, patch microperthites associated with abundant micropores, but there remain clear, optically featureless regions almost free of micropores. The interiors are intricate mixtures of optically clear, featureless regions, and turbid, patch microperthite regions. The clear, featureless regions (Or31 –47) are of remaining exsolution lamellar cryptoperthites. The zoning patterns of Fe and Ca formed by large-scale transport over the feldspar grain during the high-temperature fluid stage. They have been modified by successive transport of Fe and Ca during the later hydrothermal development of patch microperthites and finally by K-feldspathization and albitization. Cathodoluminescence images correspond to the spatial distribution patterns of Fe overprinted by these multi-stage reactions. The original composition of the alkali feldspar before the subsolidus reactions is estimated to have been ~Or34Ab65An1, and the present bulk composition after the reactions is Or40Ab59An0.5.
TACI-BLyS signaling via B-cell–dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo
Authors: Diaz-de-Durana Yaiza , Mantchev George T. , Bram Richard J. , Franco Alessandra
Published: September 2005

We demonstrated that B-cell–dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8+ T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell–deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyShigh peptide-pulsed bone marrow–derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell–deficient and TACI-deficient mice, strongly supporting a need for B-cell–DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.
Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP
Authors: Hanaoka Nobuyoshi , Kawaguchi Tatsuya , Horikawa Kentaro , Nagakura Shoichi , Mitsuya Hiroaki , Nakakuma Hideki
Published: September 2005

The mechanism by which paroxysmal nocturnal hemoglobinuria (PNH) clones expand is unknown. PNH clones harbor PIGA mutations and do not synthesize glycosylphosphatidylinositol (GPI), resulting in deficiency of GPI-linked membrane proteins. GPI-deficient blood cells often expand in patients with aplastic anemia who sustain immune-mediated marrow injury putatively induced by cytotoxic cells, hence suggesting that the injury allows PNH clones to expand selectively. We previously reported that leukemic K562 cells preferentially survived natural killer (NK) cell-mediated cytotoxicity in vitro when they acquired PIGA mutations. We herein show that the survival is ascribable to the deficiency of stress-inducible GPI-linked membrane proteins ULBP1 and ULBP2, which activate NK and T cells. The ULBPs were detected on GPI-expressing but not on GPI-deficient K562 cells. In the presence of antibodies to either the ULBPs or their receptor NKG2D on NK cells, GPI-expressing cells were as less NK sensitive as GPI-deficient cells. NK cells therefore spared ULBP-deficient cells in vitro. The ULBPs were identified only on GPI-expressing blood cells of a proportion of patients with PNH but none of healthy individuals. Granulocytes of the patients partly underwent killing by autologous cytotoxic cells, implying ULBP-associated blood cell injury. In this setting, the lack of ULBPs may allow immunoselection of PNH clones.
Tyrosine phosphorylation modulates binding preference to cyclin-dependent kinases and subcellular localization of p27Kip1 in the acute promyelocytic leukemia cell line NB4
Authors: Kardinal Christian , Dangers Marc , Kardinal Angelika , Koch Alexandra , Brandt Dominique Tobias , Tamura Teruko , Welte Karl
Published: September 2005

We have investigated the role of tyrosine phosphorylation of the cyclin-dependent kinase (cdk) inhibitor p27Kip1 using the acute promyelocytic leukemia cell line NB4 together with granulocyte colony-stimulating factor (G-CSF). Short-term G-CSF stimulation resulted in a rapid tyrosine dephosphorylation of p27Kip1 accompanied by a change in its binding preferences to cdks. On G-CSF stimulation, p27Kip1 dissociated from cdk4 and associated with cdk2. Binding assays with recombinant p27Kip1 confirmed that tyrosine-phosphorylated p27Kip1 preferentially bound to cdk4, whereas unphosphorylated protein preferentially associated with cdk2. In addition, studies with p27Kip1 point mutations revealed a decisive role of Tyr88 and Tyr89 in binding to cdk4. Furthermore, phosphorylation of Tyr88 and Tyr89 was accompanied by strong nuclear translocation of p27Kip1. Taken together, this report provides the first evidence that tyrosine phosphorylation of p27Kip1 plays a crucial role in binding to cdks and its subcellular localization. Moreover, both effects are mediated by application of G-CSF.
The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL
Authors: Teachey David T. , Obzut Dana A. , Cooperman Jonathan , Fang Junjie , Carroll Martin , Choi John K. , Houghton Peter J. , Brown Valerie I. , Grupp Stephan A.
Published: September 2005

Acute lymphoblastic leukemia (ALL) in adult patients is often resistant to current therapy, making the development of novel therapeutic agents paramount. We investigated whether mTOR inhibitors (MTIs), a class of signal transduction inhibitors, would be effective in primary human ALL. Lymphoblasts from adult patients with precursor B ALL were cultured on bone marrow stroma and were treated with CCI-779, a second generation MTI. Treated cells showed a dramatic decrease in cell proliferation and an increase in apoptotic cells, compared to untreated cells. We also assessed the effect of CCI-779 in a NOD/SCID xenograft model. We treated a total of 68 mice generated from the same patient samples with CCI-779 after establishment of disease. Animals treated with CCI-779 showed a decrease in peripheral-blood blasts and in splenomegaly. In dramatic contrast, untreated animals continued to show expansion of human ALL. We performed immunoblots to validate the inhibition of the mTOR signaling intermediate phospho-S6 in human ALL, finding down-regulation of this target in xenografted human ALL exposed to CCI-779. We conclude that MTIs can inhibit the growth of adult human ALL and deserve close examination as therapeutic agents against a disease that is often not curable with current therapy.
Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia
Authors: Brüggemann Monika , Raff Thorsten , Flohr Thomas , Gökbuget Nicola , Nakao Makoto , Droese Jo , Lüschen Silke , Pott Christiane , Ritgen Matthias , Scheuring Urban , Horst Heinz-August , Thiel Eckhard , Hoelzer Dieter , Bartram Claus R. , Kneba Michael ,   for the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia
Published: September 2005

Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10-4 or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10-4 or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.
Mathematical design of prokaryotic clone-based microarrays
Authors: Pieterse Bart , Quirijns Elisabeth J , Schuren Frank HJ , van der Werf Mariët J
Published: September 2005

Background

Clone-based microarrays, on which each spot represents a random genomic fragment, are a good alternative to open reading frame-based microarrays, especially for microorganisms for which the complete genome sequence is not available. Since the generation of a genomic DNA library is a random process, it is beforehand uncertain which genes are represented. Nevertheless, the genome coverage of such an array, which depends on different variables like the insert size and the number of clones in the library, can be predicted by mathematical approaches. When applying the classical formulas that determine the probability that a certain sequence is represented in a DNA library at the nucleotide level, massive amounts of clones would be necessary to obtain a proper coverage of the genome.

Results

This paper describes the development of two complementary equations for determining the genome coverage at the gene level. The first equation predicts the fraction of genes that is represented on the array in a detectable way and cover at least a set part (the minimal insert coverage) of the genomic fragment by which these genes are represented. The higher this minimal insert coverage, the larger the chance that changes in expression of a specific gene can be detected and attributed to that gene. The second equation predicts the fraction of genes that is represented in spots on the array that only represent genes from a single transcription unit, which information can be interpreted in a quantitative way.

Conclusion

Validation of these equations shows that they form reliable tools supporting optimal design of prokaryotic clone-based microarrays.
Optimized between-group classification: a new jackknife-based gene selection procedure for genome-wide expression data
Authors: Baty Florent , Bihl Michel P , Perrière Guy , Culhane Aedín C , Brutsche Martin H
Published: September 2005

Background

A recent publication described a supervised classification method for microarray data: Between Group Analysis (BGA). This method which is based on performing multivariate ordination of groups proved to be very efficient for both classification of samples into pre-defined groups and disease class prediction of new unknown samples. Classification and prediction with BGA are classically performed using the whole set of genes and no variable selection is required. We hypothesize that an optimized selection of highly discriminating genes might improve the prediction power of BGA.

Results

We propose an optimized between-group classification (OBC) which uses a jackknife-based gene selection procedure. OBC emphasizes classification accuracy rather than feature selection. OBC is a backward optimization procedure that maximizes the percentage of between group inertia by removing the least influential genes one by one from the analysis. This selects a subset of highly discriminative genes which optimize disease class prediction. We apply OBC to four datasets and compared it to other classification methods.

Conclusion

OBC considerably improved the classification and predictive accuracy of BGA, when assessed using independent data sets and leave-one-out cross-validation.

Availability

The R code is freely available [see Additional file 1] as well as supplementary information [see Additional file 2].
Genetic chimerism of Vitis viniferacv. Chardonnay 96 is maintained through organogenesis but not somatic embryogenesis
Authors: Bertsch Christophe , Kieffer Flore , Maillot Pascale , Farine Sibylle , Butterlin Gisèle , Merdinoglu Didier , Walter Bernard
Published: September 2005

Background

Grapevine can be a periclinal chimera plant which is composed at least of two distinct cell layers (L1, L2). When the cell layers of this plant are separated by passage through somatic embryogenesis, regenerated plants could show distinct DNA profiles and a novel phenotype which proved different from that of the parent plant.

Results

Genetically Chardonnay clone 96 is a periclinal chimera plant in which is L1 and L2 cell layers are distinct. Plants obtained via organogenesis through meristematic bulks are shown to be composed of both cell layers. However, plants regenerated through somatic embryogenesis starting from anthers or nodal explants are composed only of L1 cells. These somaclones do not show phenotypic differences to the parental clone up to three years after regeneration. Interestingly, the only somaclone showing an atypical phenotype (asymmetric leave) shows a genotypic modification.

Conclusion

These results suggest that the phenotype of Chardonnay 96 does not result from an interaction between the two distinct cell layers L1 and L2. If phenotype conformity is further confirmed, somatic embryogenesis will result in true-to-type somaclones of Chardonnay 96 and would be well suitable for gene transfer.
GB virus-C – a virus without a disease: We cannot give it chronic fatigue syndrome
Authors: Jones James F , Kulkarni Prasad S , Butera Salvatore T , Reeves William C
Published: September 2005

Background

Chronic fatigue syndrome (CFS) is an illness in search of an infectious etiology. GB virus-C (GBV-C) virus is a flavivirus with cell tropism and host defense induction qualities compatible with a role in producing the syndrome. The GBV-C genome is detectable in 4% of the population and 12% of the population is seropositive. The present study evaluated the association between infection with GBV and CFS.

Methods

We used a commercial EIA to detect antibodies against the GBV-C E2 protein and a quantitative real-time RT-PCR assay to detect active GBV-C infection. Sera were from a case control study of CFS in Atlanta, Georgia. The Fisher's exact two-tailed test was used for statistical analysis.

Results

Two of 12 CFS patients and one of 21 controls were seropositive for prior GBV-C infection and one control had viral RNA detected, indicating active infection. The results are not statistically different.

Conclusion

We found no evidence that active or past infection with GBV is associated with CFS.
Plasma lipid profiles and risk of cardiovascular disease in occupational lead exposure in Abeokuta, Nigeria
Authors: Ademuyiwa Oladipo , Ugbaja Regina Ngozi , Idumebor Florence , Adebawo Olugbenga
Published: September 2005

In order to investigate the effects of lead exposure on risk of cardiovascular disease during occupational exposure to this metal, plasma cholesterol and its fractions as high-density liporotein (HDL), low-density liporotein (LDL) and triglyceride were determined in various artisans in Abeokuta, Nigeria who have been shown to be occupationally exposed to lead and these were related to blood lead levels. Increased risk of cardiovascular disease was observed in the artisans. Total cholesterol in the artisans was between 1.5 and 2.0 times higher in the artisans than that present in controls while LDL cholesterol was between 1.6 and 2.4 times higher in the artisans when compared with control subjects [p < 0.001]. HDL cholesterol and triglyceride levels were not affected [p > 0.05]. A significant positive correlation was observed between blood lead and total cholesterol on one hand [r = 0.372; p = 3.0 × 10-5] and blood lead and LDL cholesterol on the other hand [r = 0.283; p = 0.001]. LDL/HDL cholesterol ratio was also higher in the artisans when compared with control. Blood pressure (systolic and diastolic) and other anthropometric parameters were not significantly different between the artisans and the control subjects [p > 0.05]. Results suggest that lead exposure increases cholesterol synthesis and transport to peripheral tissues whereas reverse cholesterol transport to the liver is not affected.
Using the intraoperative hand held probe without lymphoscintigraphy or using only dye correlates with higher sensory morbidity following sentinel lymph node biopsy in breast cancer: A review of the literature
Authors: Kim Suk Chul , Kim Dong Wook , Moadel Renee M , Kim Chun K , Chatterjee Samprit , Shafir Michail K , Travis Arlene , Machac Josef , Krynyckyi Borys R
Published: September 2005

Background

There are no studies that have directly investigated the incremental reduction in sensory morbidity that lymphoscintigraphy images (LS) and triangulated body marking or other skin marking techniques provide during sentinel lymph node biopsy (SLNB) compared to using only the probe without LS and skin marking or using only dye. However, an indirect assessment of this potential for additional sensory morbidity reduction is possible by extracting morbidity data from studies comparing the morbidity of SLNB to that of axillary lymph node dissection.

Methods

A literature search yielded 13 articles that had data on sensory morbidity at specific time points on pain, numbness or paresthesia from SLNB that used radiotracer and probe or used only dye as a primary method of finding the sentinel node (SN). Of these, 10 utilized LS, while 3 did not utilize LS. By matching the data in studies not employing LS to the studies that did, comparisons regarding the percentage of patients experiencing pain, numbness/paresthesia after SLNB could be reasonably attempted at a cutoff of 9 months.

Results

In the 7 studies reporting on pain after 9 months (> 9 months) that used LS (1347 patients), 13.8% of patients reported these symptoms, while in the one study that did not use LS (143 patients), 28.7% of patients reported these symptoms at > 9 months (P < 0.0001). In the 6 studies reporting on numbness and/or paresthesia at > 9 months that used LS (601 patients), 12.5% of patients reported these symptoms, while in the 3 studies that did not use LS (229 patients), 23.1% of patients reported these symptoms at > 9 months (P = 0.0002). Similar trends were also noted for all these symptoms at ≤ 9 months.

Conclusion

Because of variations in techniques and time of assessing morbidity, direct comparisons between studies are difficult. Nevertheless at a minimum, a clear trend is present: having the LS images and skin markings to assist during SLNB appears to yield more favorable morbidity outcomes for the patients compared to performing SLNB with only the probe or performing SLNB with dye alone. These results are extremely pertinent, as the main reason for performing SLNB itself in the first place is to achieve reduced morbidity.
Smoking and reproduction: The oviduct as a target of cigarette smoke
Authors: Talbot Prue , Riveles Karen
Published: September 2005

The oviduct is an exquisitely designed organ that functions in picking-up ovulated oocytes, transporting gametes in opposite directions to the site of fertilization, providing a suitable environment for fertilization and early development, and transporting preimplantation embryos to the uterus. A variety of biological processes can be studied in oviducts making them an excellent model for toxicological studies. This review considers the role of the oviduct in oocyte pick-up and embryo transport and the evidence that chemicals in both mainstream and sidestream cigarette smoke impair these oviductal functions. Epidemiological data have repeatedly shown that women who smoke are at increased risk for a variety of reproductive problems, including ectopic pregnancy, delay to conception, and infertility. In vivo and in vitro studies indicate the oviduct is targeted by smoke components in a manner that could explain some of the epidemiological data. Comparisons between the toxicity of smoke from different types of cigarettes, including harm reduction cigarettes, are discussed, and the chemicals in smoke that impair oviductal functioning are reviewed.
Amino acid residues that are important for Hyal2 function as a receptor for jaagsiekte sheep retrovirus
Authors: Duh Fuh-Mei , Dirks Clarissa , Lerman Michael I , Miller A Dusty
Published: September 2005

Background

Infection by jaagsiekte sheep retrovirus (JSRV) and by enzootic nasal tumor virus (ENTV) depends on cell-surface expression of the virus entry receptor, hyaluronidase 2 (Hyal2). Human Hyal2 binds the envelope (Env) proteins of these viruses and is functional as a receptor, but Hyal2 from mice does not bind Env nor does it mediate entry of either virus. Here we have explored the amino acid determinants that account for the difference in receptor function.

Results

Analysis of human-mouse Hyal2 chimeric proteins showed that amino acid differences responsible for the difference in Hyal2 receptor activity were localized to the central third of Hyal2. Human Hyal2 mutants containing single or double amino acid replacements with the respective mouse amino acids were generated across this region and were assayed for activity. None of the single or double mutation reduced the receptor activity of human Hyal2 by more than 10-fold, whereas mouse Hyal2 activity is reduced 1,000-fold from that of human Hyal2. While the 3-dimensional structures of mammalian Hyal2 proteins are unknown, bee venom hyaluronidase shows significant amino acid similarity to human and mouse Hyal2 and its structure has been determined. Many mutations having the largest negative effects on human Hyal2 function mapped to a small region of the bee venom hyaluronidase close to but not overlapping the active site of the enzyme, suggesting that this site represents the binding site for Env. Analysis of synonymous and non-synonymous nucleotide substitutions in the coding sequences of multiple mammalian Hyal2 proteins shows that the proteins are undergoing strong selection for amino acid conservation. We found no evidence for positive selection of amino acid changes that might reflect evolution of mammalian hosts to resist JSRV or ENTV infection.

Conclusion

These results show that the greatly reduced receptor activity of mouse Hyal2 in comparison to that of human Hyal2 is determined by multiple amino acid changes acting in concert. In particular, no one amino acid change blocks infection. However, the most important amino acids map to a small patch on a predicted 3-dimensional Hyal2 structure, which may represent the binding site for Env.
An Efficient Intrathecal Delivery of Small Interfering RNA to the Spinal Cord and Peripheral Neurons
Authors: Luo Miaw-Chyi , Zhang Dong-Qin , Ma Shou-Wu , Huang Yuan-Yuan , Shuster Sam J , Porreca Frank , Lai Josephine
Published: September 2005

We have developed a highly effective method for in vivo gene silencing in the spinal cord and dorsal root ganglia (DRG) by a cationic lipid facilitated delivery of synthetic, small interfering RNA (siRNA). A siRNA to the delta opioid receptor (DOR), or a mismatch RNA, was mixed with the transfection reagent, i-Fect™ (vehicle), and delivered as repeated daily bolus doses (0.5 μg to 4 μg) via implanted intrathecal catheter to the lumbar spinal cord of rats. Twenty-four hours after the last injection, rats were tested for antinociception by the DOR selective agonist, [D-Ala2, Glu4]deltorphin II (DELT), or the mu opioid receptor (MOR) selective agonist, [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO). Pretreatment with the siRNA, but not the mismatch RNA or vehicle alone, blocked DELT antinociception dose-dependently. The latter was concomitant with a reduction in the spinal immunoreactivity and receptor density of DOR, and in DOR transcripts in the lumbar DRG and spinal dorsal horn. Neither siRNA nor mismatch RNA pretreatment altered spinal immunoreactivity of MOR or antinociception by spinal DAMGO, and had no effect on the baseline thermal nociceptive threshold. The inhibition of function and expression of DOR by siRNA was reversed by 72 hr after the last RNA injection. The uptake of fluorescence-tagged siRNA was detected in both DRG and spinal cord. The low effective dose of siRNA/i-Fect™ complex reflects an efficient delivery of the siRNA to peripheral and spinal neurons, produced no behavioral signs of toxicity. This delivery method may be optimized for other gene targets.
Effect of a small molecule inhibitor of nuclear factor-κB nuclear translocation in a murine model of arthritis and cultured human synovial cells
Authors: Wakamatsu Kyoko , Nanki Toshihiro , Miyasaka Nobuyuki , Umezawa Kazuo , Kubota Tetsuo
Published: September 2005

A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not inhibit phosphorylation and degradation of IκB (inhibitor of nuclear factor-κB [NF-κB]) but selectively inhibits nuclear translocation of activated NF-κB. This study aimed to demonstrate the antiarthritic effect of this novel inhibitor of the NF-κB pathwayin vivoin a murine arthritis model andin vitroin human synovial cells. Collagen-induced arthritis was induced in mice, and after onset of arthritis the mice were treated with DHMEQ (5 mg/kg body weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established from patients with rheumatoid arthritis (RA), NF-κB activity was examined by electrophoretic mobility shift assays. The expression of molecules involved in RA pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The proliferative activity of the cells was estimated with tritiated thymidine incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced arthritis exhibited decreased severity of arthritis, based on the degree of paw swelling, the number of swollen joints, and radiographic and histopathologic scores, compared with the control mice treated with vehicle alone. In RA FLS stimulated with tumor necrosis factor-α, activities of NF-κB components p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix metalloproteinase-3, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. The proliferative activity of the cells was also suppressed. This is the first demonstration of an inhibitor of NF-κB nuclear translocation exhibiting a therapeutic effect on established murine arthritis, and suppression of inflammatory mediators in FLS was thought to be among the mechanisms underlying such an effect.
Explicit equilibrium modeling of transcription-factor binding and gene regulation
Authors: Granek Joshua A , Clarke Neil D
Published: September 2005

We have developed a computational model that predicts the probability of transcription factor binding to any site in the genome. GOMER (generalizable occupancy model of expression regulation) calculates binding probabilities on the basis of position weight matrices, and incorporates the effects of cooperativity and competition by explicit calculation of coupled binding equilibria. GOMER can be used to test hypotheses regarding gene regulation that build upon this physically principled prediction of protein-DNA binding.
Agricultural policy discourses in the European post-Fordist transition: neoliberalism, neomercantilism and multifunctionality
Authors: Potter Clive , Tilzey Mark
Published: September 2005

A renewal of academic interest in agricultural restructuring in western Europe raises questions about causality, processes and outcomes. In particular, the relationship between deep-set structural tendencies and policy trends and the way these are constituted in relation to, and mediated through, the agency of individual land managers and other actors is emerging as a central research concern of rural social scientists. In this paper we focus on the first part of this equation, arguing that international and European agricultural restructuring needs to be rediscovered as an essentially sociopolitical project, the outcome of a struggle for influence and power between different class fractions of capital during a long and contested transition to a post-Fordist regime of accumulation. Rather than witnessing the shift towards a postproductivist agriculture anticipated by some recent commentators, we argue that the dominant framing is in favour of a neoliberal regime of market productivism, leading to the further integration of large parts of European agriculture into agro-food circuits of capital. While the neoliberal discourse which provides the intellectual justification for this process is heavily contested by advocates of a long standing form of neomercantilism and by a more recently invented discourse of agricultural multifunctionality, the entrenched position of neoliberal ideas and framings within the World Trade Organization (WTO) means that the ideology of the free market is coming to define the terms of international, and thus European, agricultural policy reform. The recent history of reform of the Common Agricultural Policy (CAP) and wider rural policy reform in the European Union (EU) nevertheless suggests that the European policy stance is one of partial resistance to unfettered liberalization, policy-makers apparently having embarked on an attempt to combine elements of the neoliberal programme with continued commitment to state assistance in various forms. This sets the frame for the regulation of an increasingly bimodal agricultural industry, in which spaces for postproductivism and rural development are being defined and defended in public interest and public good terms but where there are few opportunities to question the enforced segregation and commodification of rural space and environmental provision that this implies.
Attachment representations in mothers with abnormal illness behaviour by proxy
Authors: Adshead Gwen , Bluglass Kerry
Published: September 2005

Background

Abnormal illness behaviour by proxy (also known as factitious illness by proxy or Munchhausen syndrome by proxy) is a type of child maltreatment, the origins of which are poorly understood.

Aims

To describe attachment representations in a cohort of mothers demonstrating abnormal illness behaviour by proxy.

Method

Sixty-seven mothers who had shown this behaviour took part in a semi-structured interview assessing their attachment representations.

Results

Only 12 mothers (18%) were rated secure in terms of their own childhood attachments. There was evidence of unresolved trauma or loss reactions in 40 mothers (60%). Eighteen mothers (27%) gave unusually disorganised and incoherent accounts of attachment relationships in their own childhoods. The frequency of these attachment categories is higher than in normal non-clinical samples.

Conclusions

Insecure attachment is a risk factor for this type of child maltreatment. Therapeutic interventions could be offered in relation to unresolved traumatic stress or bereavement responses. Further study of similar groups, such as mothers with sick children or mothers with histories of traumatic experience, would be a useful next step.
Retirement intentions of consultant psychiatrists
Authors: Eagles John M. , Addie Karen , Brown Tom
Published: September 2005

Aims and Method

Through a postal survey we sought to determine the current retirement intentions of consultant psychiatrists working in Scotland. Consultants were asked their likely date of retirement, whether they might return as a locum and what might induce them to retire later.

Results

Full data were returned by 180 consultants. The mean planned age at retirement was 58.0 years. Women intended to retire significantly earlier than men. Most respondents could be persuaded to retire later through changes in services, conditions or job content; only 7% regarded their proposed retirement date as immutable.

Clinical Implications

Early retirement among consultants is likely to contribute to an even more seriously understaffed service. It is necessary to seek national and individual changes to the factors that give rise to early retirement in psychiatry.
How to make job planning work
Authors: Wise M. E. Jan
Published: September 2005

New contracts were recently accepted across the devolved nations of the UK as the basis for all future consultant employment in the National Health Service (NHS). All existing consultants have the choice of transferring to the Terms and Conditions of Service 2003 (Department of Health, 2003) or remaining on their existing contract.
Using special interest sessions to design and implement a fatigue management group for people with multiple sclerosis
Authors: Sutherland Jane K. , Cowan Paula
Published: September 2005

Aims and Method

Special interest sessions are a means of developing additional clinical interests in higher specialist training. We investigated the educational value of developing a group treatment programme for people with multiple sclerosis as well as its benefits for participants.

Results

Feedback from those attending the groups indicated the programme was rated highly or very highly. There was a trend towards improvement in quality of life measures.

Clinical Implications

The group programme provided an excellent opportunity for shared interdisciplinary learning. The use of special interest sessions in psychiatry was important in building relationships with a department without direct psychiatric input and allowed the psychiatric trainee to acquire specific disease knowledge.
Oral Vanadium Enhances the Catabolic Effects of Central Leptin in Young Adult Rats
Authors: Wilsey Jared , Matheny Michael K. , Scarpace Philip J.
Published: September 2005

Recently, vanadium has been shown to enhance leptin signal transduction in vitro. We hypothesized that chronic oral administration of an organic vanadium complex would enhance both leptin signaling and physiological responsiveness in vivo. Three-month-old F344 × Brown Norway male rats were provided a solution containing escalating doses of vanadyl acetoacetonate (V), peaking at 60 mg/liter elemental vanadium in drinking water on the 11th d of V treatment. Although V treatment tended to suppress weight gain, absolute body weights did not significantly differ between groups after 62 d of treatment. At this point, a permanent cannula was placed into the left lateral ventricle of all animals. The cannula was connected to a sc minipump providing either 5 μg/d leptin or artificial cerebral spinal fluid (ACSF) control solution. This yielded four groups: C-ACSF, C-leptin, V-ACSF, and V-leptin. During the ensuing 26 d, weight gain was similar in C-ACSF and V-ACSF. As expected, leptin caused dramatic weight loss in C-leptin, but leptin-induced weight loss was 43% greater in V-leptin. V enhanced leptin-induced signal transducer and activator of transcription-3 phosphorylation in the hypothalamus, whereas V alone had no effect. V also augmented the leptin-induced increase in brown adipose tissue uncoupling protein-1. The effects of vanadium on responsiveness to a submaximal dose of leptin (0.25 μg/d) were also evaluated, yielding qualitatively similar results. These data demonstrate, for the first time, that chronic V administration enhances the weight-reducing effects of centrally administered leptin in young adult animals, and the mechanism appears to involve enhanced leptin signal transduction.
The Presence and Ancestral Role of Gonadotropin-Releasing Hormone in the Reproduction of Scleractinian Coral, Euphyllia ancora
Authors: Twan Wen-Hung , Hwang Jiang-Shiou , Lee Yan-Horn , Jeng Shan-Ru , Yueh Wen-Shiun , Tung Ying-Hsiu , Wu Hua-Fang , Dufour Sylvie , Chang Ching-Fong
Published: September 2005

The objectives of this study were to investigate the presence of immunoreactive GnRH (irGnRH) in scleractinian coral, Euphyllia ancora, study its seasonal variation, and evaluate its biological activity. irGnRH was detected and quantified in coral polyps. The biological activity of coral irGnRH was tested on pituitary cells from black porgy by evaluating its ability to stimulate LH release. Coral extracts (10−9–10−5m irGnRH) as well as mammalian (m) GnRH agonist (10−10–10−6m) had a similar dose-dependent effect on LH release. Furthermore, GnRH receptor antagonist dose-dependently inhibited the stimulation of LH release in response to coral extracts (10−5m irGnRH) and mGnRH agonist (10−6m). Peak levels of irGnRH (10-fold increase) were observed during the spawning period in a 3-yr investigation. Significantly higher aromatase activity and estradiol (E2) levels were also detected during the period of spawning compared with the nonreproductive season. In in vivo experiments, mGnRH agonist time- and dose-dependently stimulated aromatase activity as well as the concentrations of testosterone and E2 in free and glucuronided forms in coral. In conclusion, our data indicate that irGnRH does exist in coral, with its ability to stimulate LH release in fish. Seasonal variations of coral irGnRH, with a dramatic increase during the spawning period, concomitant to that in aromatase and E2, as well as the ability of mGnRH agonist to stimulate coral aromatase, steroidogenesis, and steroid glucuronization suggest that irGnRH plays an important role in the control of oocyte growth and mass spawning in corals.
Androgens Regulate the Immune/Inflammatory Response and Cell Survival Pathways in Rat Ventral Prostate Epithelial Cells
Authors: Asirvatham A. J. , Schmidt M. , Gao B. , Chaudhary J.
Published: September 2005

A major hurdle in understanding the role of androgens is the heterogeneity of androgen receptor (AR) expression in the prostate. Because the majority of prostate cancer arises from the AR-positive secretory luminal epithelial cells, identifying the androgen-mediated pathways in the prostate epithelium is of great significance to understanding their role in prostate pathogenesis. To meet this objective, the current study was designed to identify immediate-early genes expressed in response to the synthetic androgen R1881 in cultured rat ventral prostate epithelial cells. Rat ventral prostate epithelial cells, purified from 20-d-old rats, were cultured, and the presence of AR and the response to androgen were established. The cells were then treated with R1881 for 2 and 12 h to capture immediate-early genes in an Affymetrix-based gene chip platform. A total of 66 nonredundant genes were identified that were responsive to R1881. The functional androgen response elements were identified in the proximal promoter to determine possible molecular mechanism. Cluster analysis identified five distinct signatures of R1881-induced genes. Pathway analysis suggested that R1881 primarily influences cell proliferation/differentiation and inflammatory/immune response pathways. Androgens appear to regulate cell renewal by regulating differentiation, cell proliferation, and apoptosis. Two mutually exclusive inflammatory response pathways were observed. The interferon pathway was up-regulated, and the ILs were down-regulated. The data identified novel androgen-regulated genes (e.g. Id1, Id3, IL-6, IGF-binding protein-2 and -3, and JunB). The loss of androgen regulation of these genes can have important consequences for cellular transformation and transition to androgen-independent growth and survival.
Are stop codons recognized by base triplets in the large ribosomal RNA subunit?
Authors: LIANG HAN , LANDWEBER LAURA F. , FRESCO JACQUES R.
Published: September 2005

The precise mechanism of stop codon recognition in translation termination is still unclear. A previously published study by Ivanov and colleagues proposed a new model for stop codon recognition in which 3-nucleotide Ter-anticodons within the loops of hairpin helices 69 (domain IV) and 89 (domain V) in large ribosomal subunit (LSU) rRNA recognize stop codons to terminate protein translation in eubacteria and certain organelles. We evaluated this model by extensive bioinformatic analysis of stop codons and their putative corresponding Ter-anticodons across a much wider range of species, and found many cases for which it cannot explain the stop codon usage without requiring the involvement of one or more of the eight possible noncomplementary base pairs. Involvement of such base pairs may not be structurally or thermodynamically damaging to the model. However, if, according to the model, Ter-anticodon interaction with stop codons occurs within the ribosomal A-site, the structural stringency which that site imposes on sense codon·tRNA anticodon interaction should also extend to stop codon·Ter-anticodon interactions. Moreover, with Ter-tRNA in place of an aminoacyl-tRNA, for each of the various Ter-anticodons there is a sense codon that can interact with it preferentially by complementary and wobble base-pairing. Both these considerations considerably weaken the arguments put forth previously.
Optimal Software Development: A Control Theoretic Approach
Authors: Ji Yonghua , Mookerjee Vijay S. , Sethi Suresh P.
Published: September 2005

We study the problem of optimally allocating effort between software construction and debugging. As construction proceeds, new errors are introduced into the system. The objective is to deliver a system of the highest possible quality (fewest number of errors) subject to the constraint that N system modules are constructed in a specified duration T. If errors are not corrected during construction, then further construction can produce errors at a faster rate. To curb the growth of errors, some of the effort must be taken away from construction and assigned to testing and debugging. A key finding of this model is that the practice of alternating between pure construction and pure debugging is suboptimal. Instead, it is desirable to concurrently construct and debug the system. We extend the above model to integrate decisions traditionally considered “external” such as the time to release the product to the market with those that are typically treated as “internal” such as the division of effort between construction and debugging. Results show that integrating these decisions can yield significant reduction in the overall cost. Also, when competitive forces are strong, it may be better to release a product early (with more errors) than late (with fewer errors). Thus, underestimating the cost of errors in the product may be better than overestimating the cost.