bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cbl‐b differentially regulates activation‐induced apoptosis in T helper 1 and T helper 2 cells
Authors: Hanlon Allison , Jang Sihyug , Salgame Padmini 
Published: October 2005

SummaryWe previously reported that ligation of CD3 induces antiapoptotic signals in T helper 2 (Th2) cells, and in contrast causes Th1 cells to undergo apoptosis. Here we show that Cbl‐b is accountable for the unequal response, revealing a previously unknown cell‐specific regulatory function for the molecule. Absence of Cbl‐b resulted in resistance to activation‐induced apoptosis in murine Th1 cells following CD3 ligation, akin to what is observed in Th2 cells containing Cbl‐b. Concurrent with the apoptosis profile, CD3 ligation in the absence of Cbl‐b induced raft mobilization and cytoskeletal rearrangement in Th1 cells. Despite their ability to signal from CD3, Th2 cells did not aggregate their rafts, providing an explanation for cell‐specific activity of Cbl‐b.
MAdCAM‐1 is needed for diabetes development mediated by the T cell clone, BDC‐2·5
Authors: Phillips Jenny M. , Haskins Kathryn , Cooke Anne 
Published: October 2005

SummaryThe NOD‐derived islet‐reactive CD4+ T cell clone, BDC‐2·5, is able to transfer diabetes to neonatal non‐obese diabetic (NOD) mice but is unable to transfer disease to either adult NOD or NOD scid recipients. Transfer of diabetes to adult recipients by BDC‐2·5 is only accomplished by cotransfer of CD8+ T cells from a diabetic donor. To understand why this CD4+ T cell clone is able to mediate diabetes in neonatal but not the adult recipients we examined the ability of the clone to traffic in the different recipients. Our studies showed that MAdCAM‐1 has a very different expression pattern in the neonatal and adult pancreas. Blockade of this addressin prevents the clone from transferring diabetes to neonatal mice, suggesting that the differential pancreatic expression of MAdCAM‐1 in neonatal and adult pancreas provides an explanation of the differences in diabetes development.
The secreted form of the p40 subunit of interleukin (IL)‐12 inhibits IL‐23 functions and abrogates IL‐23‐mediated antitumour effects
Authors: Shimozato Osamu , Ugai Shin‐ichi , Chiyo Masako , Takenobu Hisanori , Nagakawa Hiroyasu , Wada Akihiko , Kawamura Kiyoko , Yamamoto Hiroshi , Tagawa Masatoshi 
Published: October 2005

SummaryInterleukin (IL)‐23 is a heterodimeric cytokine consisting of a novel p19 molecule and the p40 subunit of IL‐12. Since secreted p40 can act as an antagonist for IL‐12, we investigated whether p40 also inhibited IL‐23‐mediated immunological functions. p40 did not induce interferon (IFN)‐γ or IL‐17 production from splenocytes but impaired IL‐23‐induced cytokine production by competitive binding to the IL‐23 receptors. Furthermore, a mixed population of murine colon carcinoma Colon 26 cells transduced with the p40 gene and those transduced with the IL‐23 gene developed tumours in syngenic mice, whereas the IL‐23‐expressing Colon 26 cells were completely rejected. p40 also suppressed IFN‐γ production of antigen‐stimulated splenocytes and IL‐23‐mediated cytotoxic T‐lymphocyte activities in the mice that rejected Colon 26 cells expressing IL‐23. p40 can thereby antagonize IL‐23 and is a possible therapeutic agent for suppression of IL‐23 functions.
Induction of interferon‐γ from natural killer cells by immunostimulatory CpG DNA is mediated through plasmacytoid‐dendritic‐cell‐produced interferon‐α and tumour necrosis factor‐α
Authors: Marshall Jason D. , Heeke Darren S. , Abbate Christi , Yee Priscilla , Van Nest Gary 
Published: October 2005

SummaryImmunostimulatory sequences (ISS) that contain CpG motifs have been demonstrated to exert antipathogen and antitumour immunity in animal models through several mechanisms, including the activation of natural killer (NK) cells to secrete interferon‐γ (IFN‐γ) and to exert lytic activity. Since NK cells lack the ISS receptor TLR9, the exact pathway by which NK cells are activated by ISS is unclear. We determined that ISS‐induced IFN‐γ from NK cells is primarily dependent upon IFN‐α release from plasmacytoid dendritic cells (PDCs), which directly activates the NK cell. However, further analysis indicated that other PDC‐released soluble factor(s) may contribute to IFN‐γ induction. Indeed, tumour necrosis factor‐α (TNF‐α) was identified as a significant contributor to ISS‐mediated activation of NK cells and was observed to act in an additive fashion with IFN‐α in the induction of IFN‐γ from NK cells and to up‐regulate CD69 expression on NK cells. This activity of TNF‐α, however, was dependent upon the presence of PDC‐derived factors such as type I interferon. These results illustrate an important function for type I interferon in innate immunity, which is not only to activate effectors like NK cells directly, but also to prime them for enhanced activation by other factors such as TNF‐α.
Efficient secretion of a folded protein domain by a monomeric bacterial autotransporter
Authors: Skillman Kristen M. , Barnard Travis J. , Peterson Janine H. , Ghirlando Rodolfo , Bernstein Harris D. 
Published: October 2005

SummaryBacterial autotransporters are proteins that contain a small C‐terminal ‘β domain’ that facilitates translocation of a large N‐terminal ‘passenger domain’ across the outer membrane (OM) by an unknown mechanism. Here we used EspP, an autotransporter produced by Escherichia coli 0157:H7, as a model protein to gain insight into the transport reaction. Initially we found that the passenger domain of a truncated version of EspP (EspPΔ1‐851) was translocated efficiently across the OM. Blue Native polyacrylamide gel electrophoresis, analytical ultracentrifugation and other biochemical methods showed that EspPΔ1‐851 behaves as a compact monomer and strongly suggest that the channel formed by the β domain is too narrow to accommodate folded polypeptides. Surprisingly, we found that a folded protein domain fused to the N‐terminus of EspPΔ1‐851 was efficiently translocated across the OM. Further analysis revealed that the passenger domain of wild‐type EspP also folds at least partially in the periplasm. To reconcile these data, we propose that the EspP β domain functions primarily to target and anchor the protein and that an external factor transports the passenger domain across the OM.
A novel palmitoyl acyl transferase controls surface protein palmitoylation and cytotoxicity in Giardia lamblia
Authors: Touz María C. , Conrad John T. , Nash Theodore E. 
Published: October 2005

SummaryThe intestinal protozoan parasite Giardia lamblia undergoes surface antigenic variation whereby one of a family of structurally related variant‐specific surface proteins (VSPs) is replaced in a regulated process by another antigenically distinct VSP. All VSPs are type I membrane proteins that have a conserved hydrophobic sequence terminated by the invariant hydrophilic amino acids, CRGKA. Using transfected Giardia constitutively expressing HA‐tagged VSPH7 and incubated with radioactive [3H]palmitate, we demonstrate that the palmitate is attached to the Cys in the conserved CRGKA tail. Surface location of mutant VSPs lacking either the CRGKA tail or its Cys is identical to that of wild‐type VSPH7 but non‐palmitoylated mutants fail to undergo complement‐independent antibody specific cytotoxicity. In addition, membrane localization of non‐palmitoylated mutant VSPH7 changes from a pattern similar to rafts to non‐rafts. Palmitoyl transferases (PAT), responsible for protein palmitoylation in other organisms, often possess a cysteine‐rich domain containing a conserved DHHC motif (DHHC‐CRD). An open reading frame corresponding to a putative 50 kDa Giardia PAT (gPAT) containing a DHHC‐CRD motif was found in the Giardia genome database. Expression of epitope‐tagged gPAT using a tetracycline inducible vector localized gPAT to the plasma membrane, a pattern similar to that of VSPs. Transfection with gPAT antisense producing vectors inhibits gPAT expression and palmitoylation of VSPs in vitro confirming the function of gPAT. These results show that VSPs are palmitoylated at the cysteine within the conserved tail by gPAT and indicate an essential function of palmitoylation in control of VSP‐mediated signalling and processing.
Pyridoxine is required for post‐embryonic root development and tolerance to osmotic and oxidative stresses
Authors: Chen Hao , Xiong Liming 
Published: October 2005

SummaryPyridoxine (vitamin B6) is a cofactor required by numerous enzymes in all cellular organisms. Plants are the major source of vitamin B6 for animals, yet the biosynthesis pathway and the function of vitamin B6 in plants are not well elucidated. In this study, an Arabidopsis pyridoxine synthase gene PDX1 was characterized and its in vivo functions were investigated. The PDX1 gene was expressed in all plant parts examined and its expression level was not significantly regulated by abiotic stress or the phytohormone abscisic acid. In roots, PDX1 was highly expressed in a defined region behind the root tips that undergoes rapid cell division. The PDX1 protein was mainly associated with the plasma membrane and endomembranes, implying a potential involvement of vitamin B6 in membrane function. To reveal the in vivo role of PDX1, Arabidopsis insertional mutants were isolated. Strikingly, the pdx1 knockout mutants were impaired in root growth and early seedling development. The stunted roots resulted from both reduced cell division and elongation. Supplementation of the growth media with pyridoxine or reintroduction of the wild‐type PDX1 gene into the mutants completely restored the mutant growth, demonstrating that PDX1 is required for pyridoxine biosynthesis in planta. In addition to the developmental defects, pdx1 mutants are hypersensitive to osmotic stress and oxidative stress. These mutant seedlings had increased peroxidation of membrane lipids following UV treatment. Our study establishes a critical role of vitamin B6 in plant development and stress tolerance and suggests that vitamin B6 may represent a new class of antioxidant in plants.
Arabidopsis thaliana subcellular responses to compatible Erysiphe cichoracearum infections
Authors: Koh Serry , André Aurélie , Edwards Herb , Ehrhardt David , Somerville Shauna 
Published: October 2005

SummarySubcellular events of Erysiphe cichoracearum infections of epidermal cells were visualized in living tissues of Arabidopsis plants carrying various green fluorescent protein (GFP)‐tagged organelles via laser scanning confocal microscopy. Early in the infection sequence, cytoplasm and organelles moved towards penetration sites and accumulated near penetration pegs. Peroxisomes appeared to accumulate preferentially relative to the cytoplasm at penetration sites. Another early event, which preceded haustorium formation, was the aggregation of some GFP‐tagged plasma membrane marker proteins into rings around penetration sites, which extended across cell‐wall boundaries into neighboring cells. This feature localized to sites where papillae were deposited. The extrahaustorial membrane (EHM) encases the fungal feeding structure, the haustorium, separating it from the host cytoplasm. Eight plasma membrane markers were excluded from the EHM and remained in a collar‐like formation around the haustorial neck. These observations support the suggestions that the EHM is a unique, specialized membrane and is different from the plasma membrane. Our results suggested two possibilities for the origin of the EHM: invagination of the plasma membrane coupled with membrane differentiation; or de novo synthesis of the EHM by targeted vesicle trafficking.
Evaluation of COBAS AmpliPrep nucleic acid extraction in conjunction with COBAS AmpliScreen HBV DNA, HCV RNA and HIV‐1 RNA amplification and detection
Authors: Koppelman M. H. G. M. , Sjerps M. C. , Reesink H. W. , Cuypers H. T. M. 
Published: October 2005

Background and Objectives  This report describes the evaluation of the COBAS AmpliPrep instrument for fully automated generic nucleic acid extraction in conjunction with hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, and human immunodeficiency virus (HIV)‐1 RNA COBAS AmpliScreen amplification and detection using serial dilutions of the WHO international standards (IS) and the PeliCheck reference panels.Materials and Methods  Serial diluted samples of the WHO IS and the PeliCheck reference panels were tested 24 times to determine the HBV DNA, HCV RNA and HIV‐1 RNA detection limits by Probit analysis. The existence and extent of cross‐contamination were assessed by testing alternating high titre HBV DNA‐positive and ‐negative samples. The specificity of the AmpliPrep–AmpliScreen test for HBV was determined by testing 232 minipools consisting of six donations, all negative for HCV/HIV‐1 nucleic acid testing (NAT) and HBsAg. In addition, a HBV genotypes A–G panel was tested.Results  The respective 95% detection limits (and 95% CI) on the WHO IS and on the PeliCheck reference panels were 6·7 (4·3–13) IU/ml and 123 (68–301) gEq/ml for HBV DNA, 23 (11–106) IU/ml and 126 (84–233) gEq/ml for HCV RNA, and 187 (108–422) IU/ml and 183 (108–434) gEq/ml for HIV‐1 RNA. Based on the WHO IS and the PeliCheck reference panels, no significant differences in sensitivity for HBV and HCV were found between AmpliPrep and the licensed MultiPrep extraction method. The sensitivity of AmpliPrep–AmpliScreen for HIV‐1 was probably twofold lower as compared to the MultiPrep–AmpliScreen method. No cross contamination was observed. All 232 minipools were HBV NAT‐negative. The AmpliPrep–AmpliScreen test for HBV detected HBV genotypes A–G with equal sensitivity.Conclusions  The AmpliPrep instrument combined with the AmpliScreen assays for HBV, HCV and HIV‐1 is robust and suitable for NAT donor screening. The sensitivity criteria for HIV‐1 and HCV as defined by the Paul Ehrlich Institute and the Food and Drug Administration for minipool NAT screening are met by this system.Single sentence summary  Generic COBAS AmpliPrep nucleic acid extraction in conjunction with COBAS AmpliScreen detection for HBV, HCV and HIV‐1.
Neuronal protection by sirtuins in Alzheimer's disease
Authors: Anekonda Thimmappa S. , Reddy P. Hemachandra 
Published: October 2005

AbstractSilent information regulator 2, a member of NAD+‐dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have a role in cell survival. The science of sirtuins is an emerging field and is expected to contribute significantly to the role of sirtuins in healthy aging in humans. The role of sirtuins in neuronal protection has been studied in lower organisms, such as yeast, worms, flies and rodents. Both yeast Sir2 and mammalian sirtuin proteins are up‐regulated under calorie‐restricted and resveratrol treatments. Increased sirtuin expression protects cells from various insults. Caloric restriction and antioxidant treatments have shown useful effects in mouse models of aging and Alzheimer's disease (AD) and in limited human AD clinical trials. The role sirtuins may play in modifying and protecting neurons in patients with neurodegenerative diseases is still unknown. However, a recent report of Huntington's disease revealed that Sirtuin protects neurons in a Huntington's disease mouse model, suggesting that sirtuins may protect neurons in patients with neurodegenerative diseases, such as AD. In this review, we discuss the possible mechanisms of sirtuins involved in neuronal protection and the potential therapeutic value of sirtuins in healthy aging and AD.
Cocaine‐induced CREB phosphorylation in nucleus accumbens of cocaine‐sensitized rats is enabled by enhanced activation of extracellular signal‐related kinase, but not protein kinase A
Authors: Mattson Brandi J. , Bossert Jennifer M. , Simmons Danielle E. , Nozaki Naohito , Nagarkar Deepti , Kreuter Justin D. , Hope Bruce T. 
Published: October 2005

AbstractRepeated cocaine administration to rats outside their home cages sensitizes the behavioral effects of the drug, and enhances induction of the immediate early gene product Fos in nucleus accumbens. We hypothesized that the same treatment regimen would also enhance cocaine‐induced activation of intracellular signaling kinases that phosphorylate cyclic AMP‐regulated element‐binding protein (CREB), an important mediator of c‐fos transcription. Phosphorylation levels of extracellular signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK), calcium/calmodulin kinases (CaMKs) II and IV, and CREB were used to assess endogenous functional activity of these signaling molecules in rats behaviorally sensitized outside their home cages. Protein kinase A (PKA)‐specific phosphorylation of Ser845 in the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor subunit GluR1 was used to assess endogenous functional activity of PKA. Using western blots and immunohistochemistry, we detected cocaine‐induced CREB phosphorylation after repeated cocaine administration, but not after repeated saline administration. Using western blots and MAPK activity assays, we found that cocaine‐induced phosphorylation and activation of ERK, but not of CaMKs II or IV or GluR1, was augmented in nucleus accumbens of cocaine‐sensitized rats. Unilateral infusions of the MAPK kinase inhibitor U0126 into nucleus accumbens attenuated cocaine‐induced ERK and CREB phosphorylation in cocaine‐sensitized rats. In contrast, unilateral infusions of the PKA inhibitor Rp‐isomer of adenosine‐3′,5′‐cyclicmonophosphorothioate (Rp‐cAMPs) did not affect cocaine‐induced CREB phosphorylation. Therefore, enhanced activation of ERK, but not PKA, enables and mediates cocaine‐induced CREB phosphorylation in nucleus accumbens of rats that are sensitized by repeated cocaine administration outside their home cages.
Metamorphic history of serpentinite mylonites from the Happo ultramafic complex, central Japan
Authors: NOZAKA T. 
Published: October 2005

AbstractSerpentinite mylonites from the Happo ultramafic complex show evidence of two stages of mylonitization at different temperature conditions. Peridotite mylonites exhibit two types of olivine – porphyroclasts and neoblasts – produced at the earlier stage. The olivine neoblasts have a stretching lineation with a fabric suggesting plastic deformation along (0 1 0) [0 0 1]. In addition to the olivine fabric, the stable association of olivine, orthopyroxene and tremolite in the peridotites that survived later serpentinization, and the Si and Na contents of tremolite, suggest that the earlier mylonitization took place at temperatures between 700 and 800 °C. Later mylonitization was associated with high‐temperature serpentinization to form serpentinite mylonites. In contrast to a common type of serpentinite in orogenic belts, the serpentinite mylonites are cohesively foliated, rich in olivine and diopside, and poor in antigorite. The diopside has low Al, Cr and Na contents typical of a retrograde origin, and the olivine has a homogeneous composition except in areas subjected to contact metamorphism at a later stage. Modal composition and mineral chemistry suggest that the serpentinite mylonites were formed by a hydration reaction of tremolite and olivine to produce diopside and antigorite under stable conditions of olivine, at temperatures between 400 and 600 °C. Later‐stage mylonitization has preferentially been superimposed on the earlier‐stage mylonite zone with a common direction of foliation. The difference in temperature between the two mylonitization stages suggests that the shear zone was episodically active during the emplacement of the Happo complex. Conditions of relatively high temperature for serpentinization at a convergent plate boundary and high permeability caused by the early mylonitization favoured the formation of the serpentinite mylonites.
Effect of Cataract Surgery on Cognitive Function in Older Adults
Authors: Hall Tyler Andrew , McGwin Gerald , Owsley Cynthia 
Published: October 2005

Objectives: To assess whether cataract surgery has an effect on cognitive function in older adults.Design: Longitudinal.Setting: Assessment of patients seen in eye clinics.Participants: Patients with no cataract (n=92), patients with cataract who elected surgery (n=122), and patients with cataract who declined surgery (n=87).Measurements: At baseline and 1‐year follow‐up visits, the following information was obtained: demographic, health behavior, general health status, medication use, depressive symptoms, cognitive function, and visual function information. This information was compared within and between groups at baseline and follow‐up visits.Results: Mattis Organic Mental Syndrome Screening Examination scores at baseline and follow‐up varied across the three groups, with the cataract/no surgery group having the highest scores (more cognitive impairment) and the no‐cataract group having the lowest scores (less cognitive impairment). For the within‐group analysis, at follow‐up, the cataract/no surgery group and the cataract/surgery group had significantly less cognitive impairment (P<.001), whereas the no‐cataract group experienced no change. For those with cataract, there were no associations between changes in visual function and cognitive function.Conclusion: Improvement in cognitive function may occur after cataract surgery but cannot be attributed to the cataract surgery per se or to improved visual function. Clinicians may find this information useful when discussing the nonvisual outcomes of cataract surgery with patients.
Lack of Soluble TNF‐receptors in Women with Recurrent Spontaneous Abortion and Possibility for its Correction
Authors: Chernyshov Victor P. , Vodyanik Maxim A. , Pisareva Svetlana P. 
Published: October 2005

ProblemTumor necrosis factor (TNF) and soluble TNF receptors (sTNF‐Rs) system related with Th1 and Th2 and activity of NF‐κB/IκB regulatory system. This study was designed to compare sTNF‐R1 and sTNF‐R2 production (shedding) and levels of late activated CD8+ T‐lymphocytes in non‐pregnant (n = 30) and pregnant (n = 20) normal women and non‐pregnant (n = 20) and pregnant (n = 30) RSA women. Effects of progesterone (natural structure) injections in RSA women were studied.Methods of studyLevels of sTNF‐R1, sTNF‐R2, TNF in peripheral blood serum were detected by enzyme‐linked immunosorbent assay. Lymphocyte subsets were estimated by multicolor flow cytometry. NK cell cytotoxic activity of peripheral blood lymphocytes (PBL) in whole blood against K562 targets was determined using Europium‐release cytotoxicity assay. Mitogen‐induced proliferative response of PBL to PHA‐P, Con A and PWM were determined by standard 3H‐thymidine incorporation assay.ResultsLevels of soluble TNF‐R1 and TNF‐R2 in normal pregnancy were elevated when compared with non‐pregnant normal women and pregnant RSA women. Levels of late activated CD8+ T‐lymphocytes in normal pregnancy were decreased but no changes were detected in RSA women. After progesterone therapy (i.m. injections of 2.5% oil solution) in RSA women elevation of sTNF‐R1 and sTNF‐R2 to normal pregnancy ranges was observed. No changes in levels of late activated CD8+ T‐lymphocytes after progesterone treatment were detected.ConclusionsElevation of levels of sTNF‐R1, sTNF‐R2 and decrease of late activated cytotoxic T‐lymphocytes are pronounce markers of normal human pregnancy. In RSA women there are no elevation of sTNF‐R1 and sTNF‐R2 levels during pregnancy. This deficiency may be restored by progesterone treatment.