bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of CD94/NKG2A inhibitory receptors on CD8+T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts
Authors: Zeddou Mustapha , Rahmouni Souad , Vandamme Arnaud , Jacobs Nathalie , Frippiat Frédéric , Leonard Philippe , Schaaf-Lafontaine Nicole , Vaira Dolores , Boniver Jacques , Moutschen Michel
Published: October 2007

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+T lymphocytes and NK cells.
Amyloglucosidase enzymatic reactivity inside lipid vesicles
Authors: Li Mian , Hanford Michael J , Kim Jin-Woo , Peeples Tonya L
Published: October 2007

Efficient functioning of enzymes inside liposomes would open new avenues for applications in biocatalysis and bioanalytical tools. In this study, the entrapment of amyloglucosidase (AMG) (EC 3.2.1.3) from Aspergillus niger into dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs) was investigated. Negative-stain, freeze-fracture, and cryo-transmission electron microscopy images verified vesicle formation in the presence of AMG. Vesicles with entrapped AMG were isolated from the solution by centrifugation, and vesicle lamellarity was identified using fluorescence laser confocal microscopy. The kinetics of starch hydrolysis by AMG was modeled for two different systems, free enzyme in aqueous solution and entrapped enzyme within vesicles in aqueous suspension. For the free enzyme system, intrinsic kinetics were described by a Michaelis-Menten kinetic model with product inhibition. The kinetic constants, V

max
and K

m
, were determined by initial velocity measurements, and K

i
was obtained by fitting the model to experimental data of glucose concentration-time curves. Predicted concentration-time curves using these kinetic constants were in good agreement with experimental measurements. In the case of the vesicles, the time-dependence of product (glucose) formation was experimentally determined and simulated by considering the kinetic behavior of the enzyme and the permeation of substrate into the vesicle. Experimental results demonstrated that entrapped enzymes were much more stable than free enyzme. The entrapped enzyme could be recycled with retention of 60% activity after 3 cycles. These methodologies can be useful in evaluating other liposomal catalysis operations.
Src kinase inhibition promotes the chondrocyte phenotype
Authors: Bursell Laura , Woods Anita , James Claudine G , Pala Daphne , Leask Andrew , Beier Frank
Published: October 2007

Regulated differentiation of chondrocytes is essential for both normal skeletal development and maintenance of articular cartilage. The intracellular pathways that control these events are incompletely understood, and our ability to modulate the chondrocyte phenotype in vivo or in vitro is therefore limited. Here we examine the role played by one prominent group of intracellular signalling proteins, the Src family kinases, in regulating the chondrocyte phenotype. We show that the Src family kinase Lyn exhibits a dynamic expression pattern in the chondrogenic cell line ATDC5 and in a mixed population of embryonic mouse chondrocytes in high-density monolayer culture. Inhibition of Src kinase activity using the pharmacological compound PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d]pyrimidine) strongly reduced the number of primary mouse chondrocytes. In parallel, PP2 treatment increased the expression of both early markers (such as Sox9, collagen type II, aggrecan and xylosyltransferases) and late markers (collagen type X, Indian hedgehog and p57) markers of chondrocyte differentiation. Interestingly, PP2 repressed the expression of the Src family members Lyn, Frk and Hck. It also reversed morphological de-differentiation of chondrocytes in monolayer culture and induced rounding of chondrocytes, and reduced stress fibre formation and focal adhesion kinase phosphorylation. We conclude that the Src kinase inhibitor PP2 promotes chondrogenic gene expression and morphology in monolayer culture. Strategies to block Src activity might therefore be useful both in tissue engineering of cartilage and in the maintenance of the chondrocyte phenotype in diseases such as osteoarthritis.
Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study
Authors: Teng YK Onno , Verburg Robert J , Verpoort Kirsten N , Diepenhorst Gwendolyn MP , Bajema Ingeborg M , van Tol Maarten JD , Jol-van der Zijde Els CM , Toes Rene EM , Huizinga Tom WJ , van Laar Jacob M
Published: October 2007

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.
Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
Authors: Quaglino Ana , Schere-Levy Carolina , Romorini Leonardo , Meiss Roberto P , Kordon Edith C
Published: October 2007

Introduction

It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors.

Methods

The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed.

Results

High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells.

Conclusion

LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium.
An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation
Authors: van der Vorst Maria MJ , den Hartigh Jan , Wildschut Enno , Tibboel Dick , Burggraaf Jacobus
Published: October 2007

Introduction

The objective of the present study was to explore a continuous intravenous furosemide regimen that adapts to urine output in neonates treated with extracorporeal membrane oxygenation (ECMO).

Methods

Seven neonates admitted to a paediatric surgical intensive care unit for ECMO therapy were treated with a furosemide regimen consisting of a loading bolus (1–2 mg/kg) followed by a continuous infusion at 0.2 mg/kg per hour, which was adjusted according to the target urine production of 6 ml/kg per hour. Therapeutic drug monitoring for furosemide concentrations in blood was performed.

Results

The mean ± standard deviation furosemide dose was 0.17 ± 0.06 mg/kg per hour, 0.08 ± 0.04 mg/kg per hour and 0.12 ± 0.07 mg/kg per hour, respectively, on the first day, second day and third day of the study. The median (range of the urine production of the study subjects) urine production over the consecutive study days was 6.8 (0.8–8.4) mg/kg per hour, 6.0 (4.7–8.9) mg/kg per hour and 5.4 (3.4–10.1) ml/kg per hour. The target urine production was reached after a median time of 7 (3–37) hours. The regimen was haemodynamically well tolerated and the median furosemide serum concentration was 3.1 (0.4–12.9) μg/ml, well below the toxic level.

Conclusion

The evaluated furosemide infusion appears an effective means to reduce volume overload in neonates treated with ECMO. The data of this preliminary study suggest that the starting dose of furosemide was too high, however, because the urine output was excessive and required frequent adaptations. The results of this study therefore indicate that a novel pharmacokinetic/pharmacodynamic model needs to be developed for neonates treated with ECMO.
Transcriptional regulatory network for sexual differentiation in fission yeast
Authors: Mata Juan , Wilbrey Anna , Bähler Jürg
Published: October 2007

Background

Changes in gene expression are hallmarks of cellular differentiation. Sexual differentiation in fission yeast (Schizosaccharomyces pombe) provides a model system for gene expression programs accompanying and driving cellular specialization. The expression of hundreds of genes is modulated in successive waves during meiosis and sporulation in S. pombe, and several known transcription factors are critical for these processes.

Results

We used DNA microarrays to investigate meiotic gene regulation by examining transcriptomes after genetic perturbations (gene deletion and/or overexpression) of rep1, mei4, atf21 and atf31, which encode known transcription factors controlling sexual differentiation. This analysis reveals target genes at a genome-wide scale and uncovers combinatorial control by Atf21p and Atf31p. We also studied two transcription factors not previously implicated in sexual differentiation whose meiotic induction depended on Mei4p: Rsv2p induces stress-related genes during spore formation, while Rsv1p represses glucose-metabolism genes. Our data further reveal negative feedback interactions: both Rep1p and Mei4p not only activate specific gene expression waves (early and middle genes, respectively) but are also required for repression of genes induced in the previous waves (Ste11p-dependent and early genes, respectively).

Conclusion

These data give insight into regulatory principles controlling the extensive gene expression program driving sexual differentiation and highlight sophisticated interactions and combinatorial control among transcription factors. Besides triggering simultaneous expression of gene waves, transcription factors also repress genes in the previous wave and induce other factors that in turn regulate a subsequent wave. These dependencies ensure an ordered and timely succession of transcriptional waves during cellular differentiation.
Impaired ex Vivo Leukotriene B4 Production Characterizes the Metabolic Syndrome and Is Improved after Weight Reduction
Authors: Tsai I. J. , Beilin L. J. , Puddey I. B. , Croft K. D. , Barden A.
Published: October 2007

Context: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B4 (LTB4) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS).

Objective: We investigated whether polymorphonuclear neutrophil production of LTB4 and its metabolites 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxyl-LTB4 were altered in subjects with features of the MetS before and after weight reduction.

Design, Setting, Patients, and Intervention: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance.

Main Outcome Measures: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB4 and its metabolites were measured by HPLC.

Results: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P < 0.05). Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P < 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB4 and 20-OH-LTB4.

Conclusions: Subjects with features of the MetS have lower stimulated LTB4, which is not due to increased metabolism of LTB4. Weight reduction restored the production of neutrophil LTB4, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.
Low Body Weight Mediates the Relationship between HIV Infection and Low Bone Mineral Density: A Meta-Analysis
Authors: Bolland Mark J. , Grey Andrew B. , Gamble Greg D. , Reid Ian R.
Published: October 2007

Context: HIV infection has been associated with low bone mineral density (BMD) in many cross-sectional studies, although longitudinal studies have not demonstrated accelerated bone loss. The cross-sectional studies may have been confounded by the failure to control for low body weight in HIV-infected patients.

Objective: Our objective was to determine whether low body weight might explain the association of HIV infection with low BMD.

Data Sources: MEDLINE and EMBASE were searched for English language studies published from 1966 to March 2007, and conference abstracts prior to 2007 were hand-searched.

Study Selection: All studies reporting BMD and weight or body mass index in adult patients with HIV and a healthy age- and sex-comparable control group were included. Nine of 40 identified studies and one of 68 identified abstracts were eligible.

Data Synthesis: We adjusted for the between-groups weight differences using regression coefficients from published cohorts of healthy men and women. On average, HIV-infected patients were 5.1 kg [95% confidence interval (CI), −6.8, −3.4; P < 0.001] lighter than controls. At all skeletal sites, unadjusted BMD was lower by 4.4–7.0% in the HIV-infected groups than the controls (P < 0.01). After adjustment for body weight, residual between-groups differences in BMD were small (2.2–4.7%) [lumbar spine, −0.02 (95% CI, −0.05, 0.01) g/cm2; P = 0.12; total hip, −0.02 (95% CI, −0.04, 0.00) g/cm2; P = 0.031; femoral neck, −0.04 (95% CI, −0.07, −0.01) g/cm2; P = 0.013; and total body, −0.03 (95% CI, −0.07, 0.01) g/cm2, P = 0.11].

Conclusion: HIV-infected patients are lighter than controls and low body weight may largely account for the high prevalence of low BMD reported in HIV-infected patients. However, in the setting of current treatment practice, HIV infection per se is not a risk factor for low BMD.
Supervillin slows cell spreading by facilitating myosin II activation at the cell periphery
Authors: Takizawa Norio , Ikebe Reiko , Ikebe Mitsuo , Luna Elizabeth J.
Published: October 2007

During cell migration, myosin II modulates adhesion, cell protrusion and actin organization at the leading edge. We show that an F-actin- and membrane-associated scaffolding protein, called supervillin (SV, p205), binds directly to the subfragment 2 domains of nonmuscle myosin IIA and myosin IIB and to the N-terminus of the long form of myosin light chain kinase (L-MLCK). SV inhibits cell spreading via an MLCK- and myosin II-dependent mechanism. Overexpression of SV reduces the rate of cell spreading, and RNAi-mediated knockdown of endogenous SV increases it. Endogenous and EGFP-tagged SV colocalize with, and enhance the formation of, cortical bundles of F-actin and activated myosin II during early cell spreading. The effects of SV are reversed by inhibition of myosin heavy chain (MHC) ATPase (blebbistatin), MLCK (ML-7) or MEK (U0126), but not by inhibiting Rho-kinase with Y-27632. Flag-tagged L-MLCK co-localizes in cortical bundles with EGFP-SV, and kinase-dead L-MLCK disorganizes these bundles. The L-MLCK- and myosin-binding site in SV, SV1-171, rearranges and co-localizes with mono- and di-phosphorylated myosin light chain and with L-MLCK, but not with the short form of MLCK (S-MLCK) or with myosin phosphatase. Thus, the membrane protein SV apparently contributes to myosin II assembly during cell spreading by modulating myosin II regulation by L-MLCK.
AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane
Authors: Grohmann Annette , Tanneberger Kristina , Alzner Astrid , Schneikert Jean , Behrens Jürgen
Published: October 2007

APC is a multifunctional tumor suppressor protein that negatively controls Wnt signaling, but also regulates cell adhesion and migration by interacting with the plasma membrane and the microtubule cytoskeleton. Although the molecular basis for the microtubule association of APC is well understood, molecular mechanisms that underlie its plasma membrane localization have remained elusive. We show here that APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1), a novel membrane-associated protein that interacts with the ARM repeat domain of APC. The N-terminus of AMER1 contains two distinct phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P2]-binding domains, which mediate its localization to the plasma membrane. Overexpression of AMER1 increases APC levels and redirects APC from microtubule ends to the plasma membrane of epithelial cells. Conversely, siRNA-mediated knockdown of AMER1 reduces the overall levels of APC, promotes its association with microtubule ends in cellular protrusions and disturbs intercellular junctions. These data indicate that AMER1 controls the subcellular distribution of APC between membrane- and microtubule-associated pools, and might thereby regulate APC-dependent cellular morphogenesis, cell migration and cell-cell adhesion.
Role of the microtubule cytoskeleton in the function of the store-operated Ca2+ channel activator STIM1
Authors: Smyth Jeremy T. , DeHaven Wayne I. , Bird Gary S. , Putney James W.
Published: October 2007

We examined the role of the microtubule cytoskeleton in the localization and store-operated Ca2+ entry (SOCE) function of the endoplasmic reticulum (ER) Ca2+ sensor stromal interaction molecule 1 (STIM1) in HEK 293 cells. STIM1 tagged with an enhanced yellow fluorescent protein (EYFP-STIM1) exhibited a fibrillar localization that colocalized with endogenous α-tubulin. Depolymerization of microtubules with nocodazole caused a change from a fibrillar EYFP-STIM1 localization to one that was similar to that of the ER. Treatment of HEK 293 cells with nocodazole had a detrimental impact on SOCE and the associated Ca2+ release-activated Ca2+ current (ICRAC). This inhibition was significantly reversed in cells overexpressing EYFP-STIM1, implying that the primary inhibitory effect of nocodazole is related to STIM1 function. Surprisingly, nocodazole treatment alone induced significant SOCE and ICRAC in cells expressing EYFP-STIM1, and this was accompanied by an increase in EYFP-STIM1 fluorescence near the plasma membrane. We conclude that microtubules play a facilitative role in the SOCE signaling pathway by optimizing the localization of STIM1.
Conversion of stable RNA hairpin to a metastable dimer in frozen solution
Authors: Sun Xueguang , Li J. Michael , Wartell Roger M.
Published: October 2007

Previous studies employing a 79-nucleotide (nt) RNA indicated that this RNA could form two bands in a native polyacrylamide gel while one band was observed in a denaturing gel. This report describes an investigation on the nature of the two corresponding structures and the segment responsible for forming the slower mobility band. Sedimentation equilibrium of the 79-nt RNA was consistent with the two gel bands corresponding to monomer and dimer forms. The portion of the RNA required for dimer formation was explored using a secondary structure prediction algorithm of two 79-nt RNAs linked in a head-to-tail fashion. The predicted structure suggested that the first 21-nt at the 5′ end of each RNA formed a self-complementary duplex. A ribonuclease H assay carried out with RNA prepared as monomer (M), or a mixture of monomer and dimer (M/D), gave results consistent with the predicted M and D structures. Gel mobility experiments on 5′ and 3′ segments of the 79-nt RNA also indicated that dimer formation was due to the 21-nt 5′ end. Studies on the 21-nt RNA molecule and sequence variants showed that this sequence can form a hairpin and a dimer complex. Unexpectedly, the hairpin to dimer conversion was shown to occur at high efficiency in frozen solution, although little or no conversion was observed above 0°C. The results indicate that a freezing environment can promote formation of intermolecular RNA complexes from stable RNA hairpins, supporting the notion that this environment could have played a role in the evolution of RNA complexity.
In vitro dimerization of human immunodeficiency virus type 1 (HIV-1) spliced RNAs
Authors: Sinck Lucile , Richer Delphine , Howard Jane , Alexander Marina , Purcell Damian F.J. , Marquet Roland , Paillart Jean-Christophe
Published: October 2007

The human immunodeficiency virus type 1 (HIV-1) packages its genomic RNA as a dimer of homologous RNA molecules that has to be selected among a multitude of cellular and viral RNAs. Interestingly, spliced viral mRNAs are packaged into viral particles with a relatively low efficiency despite the fact that they contain most of the extended packaging signal found in the 5′ untranslated region of the genomic RNA, including the dimerization initiation site (DIS). As a consequence, HIV-1 spliced viral RNAs can theoretically homodimerize and heterodimerize with the genomic RNA, and thus they should directly compete with genomic RNA for packaging. To shed light on this issue, we investigated for the first time the in vitro dimerization properties of spliced HIV-1 RNAs. We found that singly spliced (env, vpr) and multispliced (tat, rev, and nef) RNA fragments are able to dimerize in vitro, and to efficiently form heterodimers with genomic RNA. Chemical probing experiments and inhibition of RNA dimerization by an antisense oligonucleotide directed against the DIS indicated that the DIS is structurally functional in spliced HIV-1 RNA, and that RNA dimerization occurs through a loop–loop interaction. In addition, by combining in vitro transcription and dimerization assays, we show that heterodimers can be efficiently formed only when the two RNA fragments are synthesized simultaneously, in the same environment. Together, our results support a model in which RNA dimerization would occur during transcription in the nucleus and could thus play a major role in splicing, transport, and localization of HIV-1 RNA.
A dynamic bulge in the U6 RNA internal stem–loop functions in spliceosome assembly and activation
Authors: McManus C. Joel , Schwartz Matthew L. , Butcher Samuel E. , Brow David A.
Published: October 2007

The highly conserved internal stem–loop (ISL) of U6 spliceosomal RNA is unwound for U4/U6 complex formation during spliceosome assembly and reformed upon U4 release during spliceosome activation. The U6 ISL is structurally similar to Domain 5 of group II self-splicing introns, and contains a dynamic bulge that coordinates a Mg++ ion essential for the first catalytic step of splicing. We have analyzed the causes of growth defects resulting from mutations in the Saccharomyces cerevisiae U6 ISL-bulged nucleotide U80 and the adjacent C67–A79 base pair. Intragenic suppressors and enhancers of the cold-sensitive A79G mutation, which replaces the C–A pair with a C–G pair, suggest that it stabilizes the ISL, inhibits U4/U6 assembly, and may also disrupt spliceosome activation. The lethality of mutations C67A and C67G results from disruption of base-pairing potential between U4 and U6, as these mutations are fully suppressed by compensatory mutations in U4 RNA. Strikingly, suppressor analysis shows that the lethality of the U80G mutation is due not only to formation of a stable base pair with C67, as previously proposed, but also another defect. A U6-U80G strain in which mispairing with position 67 is prevented grows poorly and assembles aberrant spliceosomes that retain U1 snRNP and fail to fully unwind the U4/U6 complex at elevated temperatures. Our data suggest that the U6 ISL bulge is important for coupling U1 snRNP release with U4/U6 unwinding during spliceosome activation.
The ever-expanding art curriculum is it teachable or sustainable?
Authors: Steers John
Published: October 2007

This paper examines some of the claims made for visual culture education in the context of globalisation. The history of art and design education in the United Kingdom is retraced to argue that new ideas are seldom accepted outright and that the present curriculum amounts to an array
of practices lacking a coherent philosophy that have built up over time. Some reservations about the visual culture movement are expressed and suggestions are made for a broad, intercultural curriculum.
The −374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients
Authors: Picheth Geraldo , Costantini Costantino O. , Pedrosa Fábio O. , Leme da Rocha Martinez Tania , Maltempi de Souza Emanuel
Published: October 2007

Clin Chem Lab Med 2007;45:1268–72.
Combined androgen blockade therapy can convert RT-PCR detection of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts from positive to negative in the peripheral blood of patients with clinically localized prostate cancer and increase biochemical failure-free survival after curative therapy
Authors: Lembessis Peter , Msaouel Pavlos , Halapas Antonis , Sourla Antigone , Panteleakou Zacharoula , Pissimissis Nikolaos , Milathianakis Constantine , Bogdanos John , Papaioannou Andreas , Maragoudakis Evangelos , Dardoufas Constantine , Dimopoulos Theodoros , Koutsilieris Michael
Published: October 2007

Clin Chem Leb Med 2007;45:1488–94.
A polymorphism in the resistin gene promoter is related to increased C-reactive protein levels in patients with coronary artery disease
Authors: Tang Na-Ping , Wang Lian-Sheng , Yang Li , Zhou Bo , Gu Hai-Juan , Sun Qing-Min , Cong Ri-Hong , Zhu Huai-Jun , Wang Bin
Published: October 2007

Clin Chem Lab Med 2007;45:1471–5.
Validation study of Axis-Shield carbohydrate-deficient transferrin (CDT) on ARCHITECT® chemistry analyzer
Authors: Janssen Marcel J.W. , De Gruyter Heidi L.M. , Stappers Peter M.G. , Velmans Mathieu H. , van den Ouweland Johannes M.W. , van Daal Henny , Hampsink Rene M.
Published: October 2007

Clin Chem Lab Med 2007;45:1555–8.
Huntingtin-Interacting Protein 1 Influences Worm and Mouse Presynaptic Function and ProtectsCaenorhabditis elegansNeurons against Mutant Polyglutamine Toxicity
Authors: Parker J. Alex , Metzler Martina , Georgiou John , Mage Marilyne , Roder John C. , Rose Ann M. , Hayden Michael R. , Néri Christian
Published: October 2007

Huntingtin-interacting protein 1 (HIP1) was identified through its interaction with htt (huntingtin), the Huntington's disease (HD) protein. HIP1 is an endocytic protein that influences transport and function of AMPA and NMDA receptors in the brain. However, little is known about its contribution to neuronal dysfunction in HD.

We report that theCaenorhabditis elegansHIP1 homologhipr-1modulates presynaptic activity and the abundance of synaptobrevin, a protein involved in synaptic vesicle fusion. Presynaptic function was also altered in hippocampal brain slices of HIP1−/−mice demonstrating delayed recovery from synaptic depression and a reduction in paired-pulse facilitation, a form of presynaptic plasticity. Interestingly, neuronal dysfunction in transgenic nematodes expressing mutant N-terminal huntingtin was specifically enhanced byhipr-1loss of function. A similar effect was observed with several other mutant proteins that are expressed at the synapse and involved in endocytosis, such asunc-11/AP180,unc-26/synaptojanin, andunc-57/endophilin.

Thus, HIP1 is involved in presynaptic nerve terminal activity and modulation of mutant polyglutamine-induced neuronal dysfunction. Moreover, synaptic proteins involved in endocytosis may protect neurons against amino acid homopolymer expansion.
Serial Organization of Human Behavior in the Inferior Parietal Cortex
Authors: Jubault Thomas , Ody Chrystele , Koechlin Etienne
Published: October 2007

The parietal cortex is involved in a wide range of cognitive functions in humans including associative functions between multiple sensorimotor spaces, attentional control, and working memory. Little is known, however, about the role and the functional organization of the parietal cortex in action planning and sequential cognition. Moreover, the respective contributions of parietal and frontal regions to action planning remains poorly understood. To address this issue, we designed a functional magnetic resonance imaging protocol requiring subjects to perform overlearned sequences of motor acts and sequences of cognitive tasks. The results reveal only a single bilateral region in the cerebral cortex located in the intraparietal sulcus (IPS; Brodmann's area 40) exhibiting sustained activations during the execution of both motor and task sequences. Additional analyses of phasic activations during sequence execution further suggest a functional dissociation between the left IPS, involved in representing and processing the abstract serial structure of ongoing behavioral sequences regardless of their hierarchical structure, and the right IPS, involved in preparing successive sensorimotor sets that compose such behavioral sequences. We show that this parietal system functionally differs from the frontal system that was previously identified as controlling action selection with respect to the hierarchical rather than serial structure of behavioral plans. Thus, our results reveal the central role of the bilateral intraparietal sulcus in high-order sequential cognition and suggest a major functional segregation within the frontoparietal network mediating action planning, with the frontal and parietal sector involved in processing the hierarchical and serial structure of action plans, respectively.
Reduced Sodium Current in Purkinje Neurons from NaV1.1 Mutant Mice: Implications for Ataxia in Severe Myoclonic Epilepsy in Infancy
Authors: Kalume Franck , Yu Frank H. , Westenbroek Ruth E. , Scheuer Todd , Catterall William A.
Published: October 2007

Loss-of-function mutations of NaV1.1 channels cause severe myoclonic epilepsy in infancy (SMEI), which is accompanied by severe ataxia that contributes substantially to functional impairment and premature deaths. Mutant mice lacking NaV1.1 channels provide a genetic model for SMEI, exhibiting severe seizures and premature death on postnatal day 15. Behavioral assessment indicated severe motor deficits in mutant mice, including irregularity of stride length during locomotion, impaired motor reflexes in grasping, and mild tremor in limbs when immobile, consistent with cerebellar dysfunction. Immunohistochemical studies showed that NaV1.1 and NaV1.6 channels are the primary sodium channel isoforms expressed in cerebellar Purkinje neurons. The amplitudes of whole-cell peak, persistent, and resurgent sodium currents in Purkinje neurons were reduced by 58–69%, without detectable changes in the kinetics or voltage dependence of channel activation or inactivation. Nonlinear loss of sodium current in Purkinje neurons from heterozygous and homozygous mutant animals suggested partial compensatory upregulation of NaV1.6 channel activity. Current-clamp recordings revealed that the firing rates of Purkinje neurons from mutant mice were substantially reduced, with no effect on threshold for action potential generation. Our results show that NaV1.1 channels play a crucial role in the excitability of cerebellar Purkinje neurons, with major contributions to peak, persistent, and resurgent forms of sodium current and to sustained action potential firing. Loss of these channels in Purkinje neurons of mutant mice and SMEI patients may be sufficient to cause their ataxia and related functional deficits.
Flight Initiation and Maintenance Deficits in Flies with Genetically Altered Biogenic Amine Levels
Authors: Brembs Björn , Christiansen Frauke , Pflüger Hans Joachim , Duch Carsten
Published: October 2007

Insect flight is one of the fastest, most intense and most energy-demanding motor behaviors. It is modulated on multiple levels by the biogenic amine octopamine. Within the CNS, octopamine acts directly on the flight central pattern generator, and it affects motivational states. In the periphery, octopamine sensitizes sensory receptors, alters muscle contraction kinetics, and enhances flight muscle glycolysis. This study addresses the roles for octopamine and its precursor tyramine in flight behavior by genetic and pharmacological manipulation inDrosophila. Octopamine is not the natural signal for flight initiation because flies lacking octopamine [tyramine-β-hydroxylase (TβH) null mutants] can fly. However, they show profound differences with respect to flight initiation and flight maintenance compared with wild-type controls. The morphology, kinematics, and development of the flight machinery are not impaired in TβH mutants because wing-beat frequencies and amplitudes, flight muscle structure, and overall dendritic structure of flight motoneurons are unaffected in TβH mutants. Accordingly, the flight behavior phenotypes can be rescued acutely in adult flies. Flight deficits are rescued by substituting octopamine but also by blocking the receptors for tyramine, which is enriched in TβH mutants. Conversely, ablating all neurons containing octopamine or tyramine phenocopies TβH mutants. Therefore, both octopamine and tyramine systems are simultaneously involved in regulating flight initiation and maintenance. Different sets of rescue experiments indicate different sites of action for both amines. These findings are consistent with a complex system of multiple amines orchestrating the control of motor behaviors on multiple levels rather than single amines eliciting single behaviors.
Multiple Memory Traces for Olfactory Reward Learning inDrosophila
Authors: Thum Andreas S. , Jenett Arnim , Ito Kei , Heisenberg Martin , Tanimoto Hiromu
Published: October 2007

Physical traces underlying simple memories can be confined to a single group of cells in the brain. In the flyDrosophila melanogaster, the Kenyon cells of the mushroom bodies house traces for both appetitive and aversive odor memories. The adenylate cyclase protein, Rutabaga, has been shown to mediate both traces. Here, we show that, for appetitive learning, another group of cells can additionally accommodate a Rutabaga-dependent memory trace. Localized expression ofrutabagain either projection neurons, the first-order olfactory interneurons, or in Kenyon cells, the second-order interneurons, is sufficient for rescuing the mutant defect in appetitive short-term memory. Thus, appetitive learning may induce multiple memory traces in the first- and second-order olfactory interneurons using the same plasticity mechanism. In contrast, aversive odor memory ofrutabagais rescued selectively in the Kenyon cells, but not in the projection neurons. This difference in the organization of memory traces is consistent with the internal representation of reward and punishment.
Human Immunodeficiency Virus-1/Surface Glycoprotein 120 Induces Apoptosis through RNA-Activated Protein Kinase Signaling in Neurons
Authors: Alirezaei Mehrdad , Watry Debbie D. , Flynn Claudia F. , Kiosses William B. , Masliah Eliezer , Williams Bryan R. G. , Kaul Marcus , Lipton Stuart A. , Fox Howard S.
Published: October 2007

Previous work has demonstrated that the surface glycoprotein (gp120) of human immunodeficiency virus-1 (HIV-1) can induce damage and apoptosis of neurons bothin vitroandin vivo. In this report, we provide evidence that double-stranded RNA-activated protein kinase (PKR), a stress kinase, is involved in HIV/gp120-associated neurodegeneration. In cultures of mixed cortical cells, HIV/gp120 increased the protein level of PKR. Additionally, PKR was phosphorylated in neurons but not glia after exposure to gp120. The use of two independent pharmacological inhibitors of PKR activity abrogated neuronal cell death induced by gp120. Cortical neurons from PKR knock-out mice were significantly protected from neurotoxicity induced by gp120, further validating the pivotal proapoptotic function of PKR. gp120-induced phosphorylated PKR localized prominently to neuronal nuclei; PKR inhibition or the NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate] abrogated this effect. PKR inactivation also inhibited gp120-induced caspase-3 activation, consistent with its neuroprotective effect. Finally, brain tissue from individuals diagnosed with HIV-associated dementia (HAD), but not HIV infection alone, contained the activated form of PKR, which localized predominantly to neuronal nuclei. Together, these results identify PKR as a critical mediator of gp120 neurotoxicity, suggesting that activation of PKR contributes to the neuronal injury and cell death observed in HAD.
Orexin Signaling in the Ventral Tegmental Area Is Required for High-Fat Appetite Induced by Opioid Stimulation of the Nucleus Accumbens
Authors: Zheng Huiyuan , Patterson Laurel M. , Berthoud Hans-Rudolf
Published: October 2007

The overriding of satiety and homeostatic control mechanisms by cognitive, rewarding, and emotional aspects of palatable foods may contribute to the evolving obesity crisis, but little is known about neural pathways and mechanisms responsible for crosstalk between the “cognitive” and “metabolic” brain in the control of appetite. Here we show that neural connections between the nucleus accumbens and hypothalamus might be part of this link. Using the well known model of selective stimulation of high-fat intake induced by intra-accumbens injection of the μ-opioid receptor agonistd-Ala2-N-Me-Phe4-gly5-ol-enkephalin (DAMGO), we demonstrate that orexin signaling in the ventral tegmental area is important for this reward-driven appetite to override metabolic repletion signals in presatiated rats. We further show that accumbens DAMGO in the absence of food selectively increases the proportion of orexin neurons expressing c-Fos in parts of the perifornical hypothalamus and that neural projections originating in DAMGO-responsive sites of the nucleus accumbens make close anatomical contacts with hypothalamic orexin neurons. These findings suggest that direct accumbens–hypothalamic projections can stimulate hypothalamic orexin neurons, which in turn through orexin-1 receptor signaling in the ventral tegmental area and possibly other sites interfaces with the motivational and motor systems to increase intake of palatable food.
AAA Awards Exceptional Undergraduate Anthropology Teachers Researchers
Authors: Leatherman Thomas L
Published: October 2007

•Lightfoot Brings Archaeology to Life •Chin Creates Teachable Moments
Anthropology and Environment Section
Authors: Ogden Laura
Published: October 2007

•Ecological Anthropology and Disaster Research Anthony Oliver‐Smith
Association for Africanist Anthropology
Authors: Coffman Jennifer E
Published: October 2007

•Remembering Elliot P Skinner With Bennetta Jules‐Rosette  •AfAA Awards With Bennetta Jules‐Rosette  •More AfAA at the 2007 Annual Meeting With David Turkon, Maria Cattell
Association for Black Anthropologists
Authors: Chin Elizabeth J
Published: October 2007

•Race, Globalization and Hip Hop Culture Raymond Codrington
Association for Feminist Anthropology
Authors: Upton Rebecca
Published: October 2007

•Horniness as a Social Construction Risako Ota
Association of Latina and Latino Anthropologists
Authors: Takash Paule Cruz , Nu?ez‐Janes Mariela
Published: October 2007

•ALLA Election Results •ALLA Sessions and Events in DC •Business Meetings •Multiple Section Joint Reception •Number of ALLA Sessions in DC •Alert Regarding ALLA Sessions
Biological Anthropology Section
Authors: Vitzthum Virginia J
Published: October 2007

•Honoring Len Lieberman •Bioanthropology of the Annual Review •2007 BAS Distinguished Speaker •Survival in the Twilight of the Gods A Theodore Steegmann Jr
Council for Museum Anthropology
Authors: Herold Joyce
Published: October 2007

•Free Anthropology Publication for Museum Educators Ann Kaupp
Evolutionary Anthropology Society
Authors: Shenk Mary K
Published: October 2007

•EAS Sponsored Sessions •EAS Reviewed Sessions •EAS Events •News re Human Nature Jane Lancaster  •Job Openings
General Anthropology Division
Authors: Schultz Emily
Published: October 2007

•A Fresh Look at Language Evolution
Middle East Section
Authors: Starrett Gregory
Published: October 2007

•Student Paper Awards: Welfare Reform and the Family in Turkey Berna Yazici
National Association of Student Anthropologists
Authors: Bernardo Melinda
Published: October 2007

•The Welcome Back Column •Annual Meeting Info •General Notes
Society for the Anthropology in Community Colleges
Authors: Miller Lloyd
Published: October 2007

•Annual Meeting 2007?A Brief Report Rob Edwards  •Annual Meeting 2008 Ann Kaupp
Society for the Anthropology of Europe
Authors: Smith Andrea
Published: October 2007

•Roundtable Luncheon at AAA in DC Sascha L Goluboff
Society for the Anthropology of Food and Nutrition
Authors: Chrzan Janet
Published: October 2007

•SAFN on the Web •SAFN at the Association for the Study of Food and Society Conference •Christine Wilson Student Award Submissions
Society for the Anthropology of North America
Authors: Hyatt Susan B
Published: October 2007

•"Ain't No Power Like the Power of the Youth" Jen Tilton
Society for the Anthropology of Religion
Authors: Coleman Simon
Published: October 2007

•Review of Shamans of the Foye Tree Susan M Kenyon
Society for East Asian Anthropology
Authors: Stevens Carolyn S , Yano Christine R
Published: October 2007

•A Conversation With Roger L Janelli Sue‐Je L Gage
Society for Latin American and Caribbean Anthropology
Authors: Caballero‐Arias Hortensia
Published: October 2007

•Mariana Selvas, A Mexican Anthropologist in Jail R A?da Hern?ndez Castillo
Society of Lesbian and Gay Anthropologists
Authors: Houston David L R
Published: October 2007

•A Bookish Perspective •Selecting Texts
Society for Linguistic Anthropology
Authors: Stanlaw James , Peterson Mark Allen
Published: October 2007

•A Decade of Cognitive Linguistics
Society for Medical Anthropology
Authors: Ragsdale Kathleen
Published: October 2007

•The Political Construction of Global Communicable Disease Crises: SfAA/SMA Abstract Deadline: October 15, 2007
Contesting Race and Power: Second‐Generation Dominican Youth in the New Gotham
Authors: APARICIO ANA
Published: October 2007

One of the effects of the new era of globalization has been an intensification of racialized inequalities, both globally and locally. Youth in cities like New York have been working arduously to establish projects and coalitions that challenge globalization and its consequences. This article examines social and racial justice projects in which New York based Dominican youth are involved. In their attempts to confront and challenge globalization and racism, they have begun to construct a new political identity; their work involves other people of color throughout the diaspora. What does the work of these activists tell us about the prospects of the “new contestatory politics” emerging among youth? What does their work tell us about the ways in which people reconfigure their sense of self, of political community, and social justice ideology in today's world?