bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia
Authors: Takamatsu Hiroyuki , Feng Xingmin , Chuhjo Tatsuya , Lu Xuzhang , Sugimori Chiharu , Okawa Katsuya , Yamamoto Miyuki , Iseki Shoichi , Nakao Shinji 
Published: November 2006

AbstractTo identify novel autoantibodies in acquired aplastic anemia (AA), we screened the sera of patients with AA possessing small populations of paroxysmal nocturnal hemoglobinuria (PNH)–type cells for the presence of antibodies (Abs) which recognize proteins derived from a leukemia cell line, UT-7. Immunoblotting using proteins derived from lysates or culture supernatants of UT-7 cells revealed the presence of IgG Abs specific to an 80-kDa protein. Peptide mass fingerprinting identified this 80-kDa protein as moesin. Enzyme-linked immunosorbent assay (ELISA) using recombinant moesin showed high titers of antimoesin Abs in 25 (37%) of 67 patients with AA. Moesin was secreted from several myeloid leukemia cell lines other than UT-7, such as OUN-1 and K562, as an exosomal protein. The presence of antimoesin Abs was significantly correlated with the presence of PNH-type cells and antidiazepam-binding inhibitor-related protein-1 (DRS-1) Abs. Patients with AA that did not show any of these 3 markers tended to respond poorly to immunosuppressive therapy. These findings suggest that a B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with AA and that detection of antimoesin Abs in combination with other markers may be useful in diagnosing immune pathophysiology in patients with AA.
A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease
Authors: MacMillan Margaret L. , Couriel Daniel , Weisdorf Daniel J. , Schwab Gisela , Havrilla Nancy , Fleming Thomas R. , Huang Saling , Roskos Lorin , Slavin Shimon , Shadduck Richard K. , DiPersio John , Territo Mary , Pavletic Steve , Linker Charles , Heslop Helen E. , Joachim Deeg H. , Blazar Bruce R. 
Published: November 2006

Abstract
Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.
Regulation of protein synthesis by the heme-regulated eIF2α kinase: relevance to anemias
Authors: Chen Jane-Jane 
Published: November 2006

AbstractDuring erythroid differentiation and maturation, it is critical that the 3 components of hemoglobin, α-globin, β-globin, and heme, are made in proper stoichiometry to form stable hemoglobin. Heme-regulated translation mediated by the heme-regulated inhibitor kinase (HRI) provides one major mechanism that ensures balanced synthesis of globins and heme. HRI phosphorylates the α-subunit of eukaryotic translational initiation factor 2 (eIF2α) in heme deficiency, thereby inhibiting protein synthesis globally. In this manner, HRI serves as a feedback inhibitor of globin synthesis by sensing the intracellular concentration of heme through its heme-binding domains. HRI is essential not only for the translational regulation of globins, but also for the survival of erythroid precursors in iron deficiency. Recently, the protective function of HRI has also been demonstrated in murine models of erythropoietic protoporphyria and β-thalassemia. In these 3 anemias, HRI is essential in determining red blood cell size, number, and hemoglobin content per cell. Translational regulation by HRI is critical to reduce excess synthesis of globin proteins or heme under nonoptimal disease states, and thus reduces the severity of these diseases. The protective role of HRI may be more common among red cell disorders.
Hlx homeobox transcription factor negatively regulates interferon-γ production in monokine-activated natural killer cells
Authors: Becknell Brian , Hughes Tiffany L. , Freud Aharon G. , Blaser Bradley W. , Yu Jianhua , Trotta Rossana , Mao Hsiaoyin C. , Caligiuri de Jesús Marie L. , Alghothani Mohamad , Benson Don M. , Lehman Amy , Jarjoura David , Perrotti Danilo , Bates Michael D. , Caligiuri Michael A. 
Published: November 2006

AbstractNatural killer (NK) cells contribute to host immunity, including tumor surveillance, through the production of interferon gamma (IFN-γ). Although there is some knowledge about molecular mechanisms that induce IFN-γ in NK cells, considerably less is known about the mechanisms that reduce its expression. Here, we investigate the role of the Hlx transcription factor in IFN-γ production by NK cells. Hlx expression is induced in monokine-activated NK cells, but with delayed kinetics compared to IFN-γ. Ectopic Hlx expression decreases IFN-γ synthesis in primary human NK cells and IFN-γ promoter activity in an NK-like cell line. Hlx protein levels inversely correlate with those of STAT4, a requisite factor for optimal IFN-γ transcription. Mechanistically, we provide evidence indicating that Hlx overexpression accelerates dephosphorylation and proteasome-dependent degradation of the active Y693-phosphorylated form of STAT4. Thus, Hlx expression in activated NK cells temporally controls and limits the monokine-induced production of IFN-γ, in part through the targeted depletion of STAT4.
Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-κB–regulated gene products and TAK1-mediated NF-κB activation
Authors: Sethi Gautam , Ahn Kwang Seok , Pandey Manoj K. , Aggarwal Bharat B. 
Published: November 2006

AbstractCelastrol, a quinone methide triterpene derived from the medicinal plant Tripterygium wilfordii, has been used to treat chronic inflammatory and autoimmune diseases, but its mechanism is not well understood. Therefore, we investigated the effects of celastrol on cellular responses activated by TNF, a potent proinflammatory cytokine. Celastrol potentiated the apoptosis induced by TNF and chemotherapeutic agents and inhibited invasion, both regulated by NF-κB activation. We found that TNF induced the expression of gene products involved in antiapoptosis (IAP1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin), proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression. Because these gene products are regulated by NF-κB, we postulated that celastrol mediates its effects by modulating the NF-κB pathway. We found that celastrol suppressed both inducible and constitutive NF-κB activation. Celastrol was found to inhibit the TNF-induced activation of IκBα kinase, IκBα phosphorylation, IκBα degradation, p65 nuclear translocation and phosphorylation, and NF-κB–mediated reporter gene expression. Recent studies indicate that TNF-induced IKK activation requires activation of TAK1, and we indeed found that celastrol inhibited the TAK1-induced NF-κB activation. Overall, our results suggest that celastrol potentiates TNF-induced apoptosis and inhibits invasion through suppression of the NF-κB pathway.
Novel methods for secondary structure determination using low wavelength (VUV) circular dichroism spectroscopic data
Authors: Lees Jonathan G , Miles Andrew J , Janes Robert W , Wallace B A 
Published: November 2006

Abstract

Background
Circular Dichroism (CD) spectroscopy is a widely used method for studying protein structures in solution. Modern synchrotron radiation CD (SRCD) instruments have considerably higher photon fluxes than do conventional lab-based CD instruments, and hence have the ability to routinely measure CD data to much lower wavelengths. Recently a new reference dataset of SRCD spectra of proteins of known structure, designed to cover secondary structure and fold space, has been produced which includes low wavelength (vacuum ultraviolet – VUV) data. However, the existing algorithms used to calculate protein secondary structures from CD data have not been designed to take optimal advantage of the additional information in these low wavelength data.

Results
In this study, we have optimised secondary structure calculation methods based on the low wavelength CD data by examining existing algorithms and secondary structure assignment schemes, and then developing new methods which have produced clear improvements in prediction accuracy, especially for beta-sheet components. We have further shown that if precise measurements of protein concentrations, and therefore spectral magnitudes, are not available, the inclusion of the low wavelength data will significantly improve the analyses. However, we have also demonstrated that the new reference dataset, methods, and assignments can also improve the analyses of conventional circular dichroism data, even if the low wavelength data is not available.

Conclusion
VUV CD data include important information on protein structure which can be exploited with the algorithms and methodologies described.
Hyaluronan- and RNA-binding deubiquitinating enzymes of USP17 family members associated with cell viability
Authors: Shin Ju-Mi , Yoo Kyong-Jai , Kim Myung-Sun , Kim Dongku , Baek Kwang-Hyun 
Published: November 2006

Abstract

Background
Protein degradation by the ubiquitin system plays a crucial role in numerous cellular signaling pathways. Deubiquitination, a reversal of ubiquitination, has been recognized as an important regulatory step in the ubiquitin-dependent degradation pathway.

Results
While identifying putative ubiquitin specific protease (USP) enzymes that contain a conserved Asp (I) domain in humans, 4 USP17 subfamily members, highly homologous to DUB-3, have been found (USP17K, USP17L, USP17M, and USP17N), from human chorionic villi. Expression analysis showed that USP17 transcripts are highly expressed in the heart, liver, and pancreas and are expressed moderately in various human cancerous cell lines. Amino acid sequence analysis revealed that they contain the highly conserved Cys, His, and Asp domains which are responsible for the deubiquitinating activity. Biochemical enzyme assays indicated that they have deubiquitinating activity. Interestingly, the sequence analysis showed that these proteins, with exception of USP17N, contain the putative hyaluronan/RNA binding motifs, and cetylpyridinium chloride (CPC)-precipitation analysis confirmed the association between these proteins and intracellular hyaluronan and RNA.

Conclusion
Here, we report that the overexpression of these proteins, with exception of USP17N, leads to apoptosis, suggesting that the hyaluronan and RNA binding motifs in these enzymes play an important role in regulating signal transduction involved in cell death.
In silico and microarray-based genomic approaches to identifying potential vaccine candidates against Leptospira interrogans
Authors: Yang Hong-Liang , Zhu Yong-Zhang , Qin Jin-Hong , He Ping , Jiang Xu-Cheng , Zhao Guo-Ping , Guo Xiao-Kui 
Published: November 2006

AbstractBackgroundCurrently available vaccines against leptospirosis are of low efficacy, have an unacceptable side-effect profile, do not induce long-term protection, and provide no cross-protection against the different serovars of pathogenic leptospira. The current major focus in leptospirosis research is to discover conserved protective antigens that may elicit longer-term protection against a broad range ofLeptospira. There is a need to screen vaccine candidate genes in the genome ofLeptospira interrogans.ResultsBioinformatics, comparative genomic hybridization (CGH) analysis and transcriptional analysis were used to identify vaccine candidates in the genome ofL. interrogansserovar Lai strain #56601. Of a total of 4727 open reading frames (ORFs), 616 genes were predicted to encode surface-exposed proteins by P-CLASSIFIER combined with signal peptide prediction, α-helix transmembrane topology prediction, integral β-barrel outer membrane protein and lipoprotein prediction, as well as by retaining the genes shared by the two sequencedL. interrogansgenomes and by subtracting genes with human homologues. A DNA microarray ofL. interrogansstrain #56601 was constructed for CGH analysis and transcriptome analysisin vitro. Three hundred and seven differential genes were identified in ten pathogenic serovars by CGH; 1427 genes had high transcriptional levels (Cy3 signal ≥ 342 and Cy5 signal ≥ 363.5, respectively). There were 565 genes in the intersection between the set encoding surface-exposed proteins and the set of 307 differential genes. The number of genes in the intersection between this set of 565 and the set of 1427 highly transcriptionally active genes was 226. These 226 genes were thus identified as putative vaccine candidates. The proteins encoded by these genes are not only potentially surface-exposed in the bacterium, but also conserved in two sequencedL. interrogans. Moreover, these genes are conserved among ten epidemic serovars in China and have high transcriptional levelsin vitro.ConclusionOf the 4727 ORFs in the genome ofL. interrogans, 226 genes were identified as vaccine candidates by bioinformatics, CGH and transcriptional analysis on the basis of the theory of reverse vaccinology. The proteins encoded by these genes might be useful as vaccine candidates as well as for diagnosis of leptospirosis.
Determinants for receiving acupuncture for LBP and associated treatments: a prospective cohort study
Authors: Chenot Jean-François , Becker Annette , Leonhardt Corinna , Keller Stefan , Donner-Banzhoff Norbert , Baum Erika , Pfingsten Michael , Hildebrandt Jan , Kochen Michael M , Basler Heinz-Dieter 
Published: November 2006

Abstract
Background
Acupuncture is a frequently used but controversial adjunct to the treatment of chronic low back pain (LBP). Acupuncture is now considered to be effective for chronic LBP and health care systems are pressured to make a decision whether or not acupuncture should be covered. It has been suggested that providing such services might reduce the use of other health care services. Therefore, we explored factors associated with acupuncture treatment for LBP and the relation of acupuncture with other health care services.

Methods
This is a post hoc analysis of a longitudinal prospective cohort study. General practitioners (GPs) recruited consecutive adult patients with LBP. Data on physical function, subjective mood and utilization of health care services was collected at the first consultation and at follow-up telephone interviews for a period of twelve months.

Results
A total of 179 (13 %) out of 1,345 patients received acupuncture treatment. The majority of those (59 %) had chronic LBP. Women and elderly patients were more likely to be given acupuncture. Additional determinants of acupuncture therapy were low functional capacity and chronicity of pain. Chronic (vs. acute) back pain OR 1.6 (CL 1.4–2.9) was the only significant disease-related factor associated with the treatment. The strongest predictors for receiving acupuncture were consultation with a GP who offers acupuncture OR 3.5 (CL 2.9–4.1) and consultation with a specialist OR 2.1 (CL 1.9–2.3). After adjustment for patient characteristics, acupuncture remained associated with higher consultation rates and an increased use of other health care services like physiotherapy.

Conclusion
Receiving acupuncture for LBP depends mostly on the availability of the treatment. It is associated with increased use of other health services even after adjustment for patient characteristics. In our study, we found that receiving acupuncture does not offset the use of other health care resources. A significant proportion of patients who received did not meet the so far only known selection criterion (chonicity). Acupuncture therapy might be a reflection of helplessness in both patients and health care providers.
CXCL1/KC and CXCL5/LIX are selectively produced by corneal fibroblasts and mediate neutrophil infiltration to the corneal stroma in LPS keratitis
Authors: Lin Michelle , Carlson Eric , Diaconu Eugenia , Pearlman Eric 
Published: November 2006

AbstractThe severity of corneal inflammation depends on the activity of infiltrating neutrophils responding to chemotactic factors such as CXC chemokines. This study examines the relative contribution of CXCL1/keratinocyte-derived chemokine (KC), CXCL2/monocyte-inhibitory protein-2 (MIP-2), and CXCL5/LPS-induced chemokine (LIX) in neutrophil recruitment to the corneal stroma during LPS keratitis, where neutrophils infiltrate the corneal stroma at 6 h after LPS injection and peak at 24 h. Consistent with this timeframe, KC was detected after 3 h, reached peak levels at 24 h, and decreased thereafter. In contrast, LIX production was not detected until 8 h after injection and peaked at 24 h. MIP-2 was detected at 3 h but did not reach the levels of KC and LIX. Cell types associated with corneal inflammation produced markedly different chemokines in vitro: Murine corneal fibroblasts (MK/T-1) produced LIX and KC in response to LPS but did not produce MIP-2, whereas peritoneal macrophages and neutrophils produced MIP-2 and KC but did not produce LIX. To determine the role of these chemokines in neutrophil recruitment to the cornea, anti-LIX, anti-KC, or anti-MIP-2 was injected into the corneal stroma of enhanced GFP chimeric mice prior to LPS, and total cell and neutrophil infiltration was examined. Antibody to LIX and KC, injected individually or in combination, significantly inhibited neutrophil recruitment to the cornea, whereas anti-MIP-2 had no inhibitory effect. Together, these findings demonstrate cell-specific production of CXC chemokines and show that LIX and KC mediate neutrophil recruitment into the cornea during LPS keratitis.
Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis
Authors: Somma Paolo , Ristori Giovanni , Battistini Luca , Cannoni Stefania , Borsellino Giovanna , Diamantini Adamo , Salvetti Marco , Sorrentino Rosa , Fiorillo Maria Teresa 
Published: November 2006

AbstractAutoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS and T cell repertoire, peripheral blood CD4+ and CD8+ T lymphocytes and their CCR7+/CCR7– subsets from five pairs of identical twins (four discordant and one concordant for MS; none of which had taken disease-modifying therapy) were compared by TCR β-chain (TCRB) complementary-determining region 3 (CDR3) spectratyping. CD4+ T cells generally showed a Gaussian distribution, whereas CD8+ T cells exhibited subject-specific, widely skewed TCR spectratypes. There was no correlation between CD8+ T cell oligoclonality and disease. Sequencing of predominant spectratype expansions revealed shared TCRB-CDR3 motifs when comparing inter- and/or intrapair twin members. In many cases, these sequences were homologous to published TCRs, specific for viruses implicated in MS pathogenesis, CNS autoantigens, or copaxone [glatiramer acetate (GA)], implying the occurrence of naturally GA-responding CD8+ T cells. It is notable that these expanded T cell clones with putative pathogenic or regulatory properties were present in the affected as well as in the healthy subject, thus suggesting the existence of a “MS predisposing trait” shared by co-twins discordant for MS.
Jumping performance of froghopper insects
Authors: Burrows Malcolm 
Published: November 2006

SUMMARYThe kinematics of jumping in froghopper insects were analysed from high speed sequences of images captured at rates up to 8000 s-1. In a jump, the attitude of the body is set by the front and middle legs, and the propulsion is delivered by rapid and synchronous movements of the hind legs that are 1.5 times longer than the other legs, but are only about half the length of the body and represent just 2% of the body mass. The wings are not moved and the front and middle legs may be raised off the ground before take-off. The hind legs are first cocked by a slow levation of the trochantera about the coxae so that the femora are pressed against the ventral, indented wall of the thorax, with the femoro-tibial joints tucked between the middle legs and body. Only the tips of the hind tarsi are in contact with the ground. In this position, the hind legs stay motionless for 1-2 s. Both trochantera are then synchronously and rapidly depressed about the coxae at rotational velocities of 75 500 deg. s-1 and the tibiae extended, to launch a jump that in Philaenus reaches a height of 700 mm, or 115 body lengths.In the best jumps by Philaenus, take-off occurs within 0.875 ms of the start of movements of the hind legs at a peak velocity of 4.7 m s-1 and involves an acceleration of 5400 m s-2,equivalent to 550 times gravity. This jumping performance requires an energy output of 136 μJ, a power output of 155 mW and exerts a force of 66 mN.
Regulation of troponin T expression during muscle development in sea breamSparus auratusLinnaeus: the potential role of thyroid hormones
Authors: Campinho M. A. , Sweeney G. E. , Power D. M. 
Published: November 2006

SUMMARYIn the sea bream Sparus auratus three stage-specific fast troponin T (fTnT) isoforms have been cloned and correspond to embryonic-, larval- and adult-specific isoforms. Characterisation, using database searches, of the putative genomic organisation of Fugu rubripes and Tetraodon nigroviridis fTnT indicates that alternative exon splicing in the 5 region of the gene generates the different isoforms. Moreover, comparison of teleost fTnTs suggests that alternative splicing of fTnT appears to be common in teleosts. A different temporal expression pattern for each fTnT splice varotnt is found during sea bream development and probably relates to differing functional demands, as a highly acidic embryonic form (pI 5.16) is substituted by a basic larval form (pI 9.57). Thyroid hormones (THs), which play an important regulatory role in muscle development in flatfish and tetrapods,appear also to influence TnT gene expression in the sea bream. However, THs have a divergent action on different sea bream TnT genes and although the slow isoform (sTnT1) is TH-responsive, fTnT, sTnT2 and the itronless isoform (iTnT) are unaffected. The present results taken together with those published for flatfish seem to suggest differences may exist in the regulation of larval muscle development in teleosts.