bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TAR Hairpin of Human Immunodeficiency Virus Type 1 Can Be Deleted When Not Required for Tat-Mediated Activation of Transcription
Authors: Das Atze T. , Harwig Alex , Vrolijk Martine M. , Berkhout Ben 
Published: May 2007

ABSTRACT
The human immunodeficiency virus type 1 (HIV-1) RNA genome contains a terminal repeat (R) region that encodes the transacting responsive (TAR) hairpin, which is essential for Tat-mediated activation of gene expression. TAR has also been implicated in several other processes during viral replication, including translation, dimerization, packaging, and reverse transcription. However, most studies in which replication of TAR-mutated viruses was analyzed were complicated by the dominant negative effect of the mutations on transcription. We therefore used an HIV-1 variant that does not require TAR for transcription to reinvestigate the role of TAR in HIV-1 replication. We demonstrate that this virus can replicate efficiently upon complete deletion of TAR. Furthermore, evolution of a TAR-deleted variant in long-term cultures indicates that HIV-1 requires a stable stem-loop structure at the start of the viral transcripts in which the 5′-terminal nucleotides are base paired. This prerequisite for efficient replication can be fulfilled by the TAR hairpin but also by unrelated stem-loop structures. We therefore conclude that TAR has no essential function in HIV-1 replication other than to accommodate Tat-mediated activation of transcription.
Generation of Infectious Molecular Clones of Simian Immunodeficiency Virus from Fecal Consensus Sequences of Wild Chimpanzees
Authors: Takehisa Jun , Kraus Matthias H. , Decker Julie M. , Li Yingying , Keele Brandon F. , Bibollet-Ruche Fréderic , Zammit Kenneth P. , Weng Zhiping , Santiago Mario L. , Kamenya Shadrack , Wilson Michael L. , Pusey Anne E. , Bailes Elizabeth , Sharp Paul M. , Shaw George M. , Hahn Beatrice H. 
Published: May 2007

ABSTRACT

Studies of simian immunodeficiency viruses (SIVs) in their endangered primate hosts are of obvious medical and public health importance, but technically challenging. Although SIV-specific antibodies and nucleic acids have been detected in primate fecal samples, recovery of replication-competent virus from such samples has not been achieved. Here, we report the construction of infectious molecular clones of SIVcpz from fecal viral consensus sequences. Subgenomic fragments comprising a complete provirus were amplified from fecal RNA of three wild-living chimpanzees and sequenced directly. One set of amplicons was concatenated using overlap extension PCR. The resulting clone (TAN1.24) contained intact genes and regulatory regions but was replication defective. It also differed from the fecal consensus sequence by 76 nucleotides. Stepwise elimination of all missense mutations generated several constructs with restored replication potential. The clone that yielded the most infectious virus (TAN1.910) was identical to the consensus sequence in both protein and long terminal repeat sequences. Two additional SIVcpz clones were constructed by direct synthesis of fecal consensus sequences. One of these (TAN3.1) yielded fully infectious virus, while the second one (TAN2.69) required modification at one ambiguous site in the viral
pol
gene for biological activity. All three reconstructed proviruses produced infectious virions that replicated in human and chimpanzee CD4
+
T cells, were CCR5 tropic, and resembled primary human immunodeficiency virus type 1 isolates in their neutralization phenotype. These results provide the first direct evidence that naturally occurring SIVcpz strains already have many of the biological properties required for persistent infection of humans, including CD4 and CCR5 dependence and neutralization resistance. Moreover, they outline a new strategy for obtaining medically important “SIV isolates” that have thus far eluded investigation. Such isolates are needed to identify viral determinants that contribute to cross-species transmission and host adaptation.
Murine Cytomegalovirus Major Immediate-Early Enhancer Region Operating as a Genetic Switch in Bidirectional Gene Pair Transcription
Authors: Simon Christian O. , Kühnapfel Birgit , Reddehase Matthias J. , Grzimek Natascha K. A. 
Published: May 2007

ABSTRACT

Enhancers are defined as DNA elements that increase transcription when placed in any orientation relative to a promoter. The major immediate-early (MIE) enhancer region of murine cytomegalovirus is flanked by transcription units
ie1/3
and
ie2
, which are transcribed in opposite directions. We have addressed the fundamental mechanistic question of whether the enhancer synchronizes transcription of the bidirectional gene pair (synchronizer model) or whether it operates as a genetic switch, enhancing transcription of either gene in a stochastic alternation (switch model). Clonal analysis of cytokine-triggered, transcription factor-mediated MIE gene expression from latent viral genomes provided evidence in support of the switch model.
Poliovirus Induces Bax-Dependent Cell Death Mediated by c-Jun NH
2
-Terminal Kinase
Authors: Autret Arnaud , Martin-Latil Sandra , Mousson Laurence , Wirotius Aurélie , Petit Frédéric , Arnoult Damien , Colbère-Garapin Florence , Estaquier Jérôme , Blondel Bruno 
Published: May 2007

ABSTRACT

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome
c
release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome
c
release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH
2
-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome
c
release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level.
Coincidence Theorems, Generalized Variational Inequality Theorems, and Minimax Inequality Theorems for the "Equation missing" -Mapping on "Equation missing" -Convex Spaces
Authors: Chen Chi-Ming , Chang Tong-Huei , Liao Ya-Pei 
Published: May 2007

AbstractWe establish some coincidence theorems, generalized variational inequality theorems, and minimax inequality theorems for the family "Equation missing"-KKM "Equation missing" and the "Equation missing"-mapping on "Equation missing"-convex spaces.
Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia
Authors: Link Daniel C. , Kunter Ghada , Kasai Yumi , Zhao Yu , Miner Tracie , McLellan Michael D. , Ries Rhonda E. , Kapur Deepak , Nagarajan Rakesh , Dale David C. , Bolyard Audrey Anna , Boxer Laurence A. , Welte Karl , Zeidler Cornelia , Donadieu Jean , Bellanné-Chantelot Christine , Vardiman James W. , Caligiuri Michael A. , Bloomfield Clara D. , DiPersio John F. , Tomasson Michael H. , Graubert Timothy A. , Westervelt Peter , Watson Mark , Shannon William , Baty Jack , Mardis Elaine R. , Wilson Richard K. , Ley Timothy J. 
Published: May 2007

AbstractSevere congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Like most other bone marrow failure syndromes, it is associated with a marked propensity to transform into a myelodysplastic syndrome (MDS) or acute leukemia, with a cumulative rate of transformation to MDS/leukemia that exceeds 20%. The genetic (and/or epigenetic) changes that contribute to malignant transformation in SCN are largely unknown. In this study, we performed mutational profiling of 14 genes previously implicated in leukemogenesis using 14 MDS/leukemia samples from patients with SCN. We used high-throughput exon-based resequencing of whole-genome–amplified genomic DNA with a semiautomated method to detect mutations. The sensitivity and specificity of the sequencing pipeline was validated by determining the frequency of mutations in these 14 genes using 188 de novo AML samples. As expected, mutations of tyrosine kinase genes (FLT3, KIT, and JAK2) were common in de novo AML, with a cumulative frequency of 30%. In contrast, no mutations in these genes were detected in the SCN samples; instead, mutations of CSF3R, encoding the G-CSF receptor, were common. These data support the hypothesis that mutations of CSF3R may provide the “activated tyrosine kinase signal” that is thought to be important for leukemogenesis.
Reconstruction of human protein interolog network using evolutionary conserved network
Authors: Huang Tao-Wei , Lin Chung-Yen , Kao Cheng-Yan 
Published: May 2007

Abstract

Background
The recent increase in the use of high-throughput two-hybrid analysis has generated large quantities of data on protein interactions. Specifically, the availability of information about experimental protein-protein interactions and other protein features on the Internet enables human protein-protein interactions to be computationally predicted from co-evolution events (interolog). This study also considers other protein interaction features, including sub-cellular localization, tissue-specificity, the cell-cycle stage and domain-domain combination. Computational methods need to be developed to integrate these heterogeneous biological data to facilitate the maximum accuracy of the human protein interaction prediction.

Results
This study proposes a relative conservation score by finding maximal quasi-cliques in protein interaction networks, and considering other interaction features to formulate a scoring method. The scoring method can be adopted to discover which protein pairs are the most likely to interact among multiple protein pairs. The predicted human protein-protein interactions associated with confidence scores are derived from six eukaryotic organisms – rat, mouse, fly, worm, thale cress and baker's yeast.

Conclusion
Evaluation results of the proposed method using functional keyword and Gene Ontology (GO) annotations indicate that some confidence is justified in the accuracy of the predicted interactions. Comparisons among existing methods also reveal that the proposed method predicts human protein-protein interactions more accurately than other interolog-based methods.
Exploring cellular memory molecules marking competent and active transcriptions
Authors: Xin Li , Zhou Guo-Ling , Song Wei , Wu Xue-Song , Wei Gong-Hong , Hao De-Long , Lv Xiang , Liu De-Pei , Liang Chih-Chuan 
Published: May 2007

Abstract

Background
Development in higher eukaryotes involves programmed gene expression. Cell type-specific gene expression is established during this process and is inherited in succeeding cell cycles. Higher eukaryotes have evolved elegant mechanisms by which committed gene-expression states are transmitted through numerous cell divisions. Previous studies have shown that both DNase I-sensitive sites and the basal transcription factor TFIID remain on silenced mitotic chromosomes, suggesting that certain trans-factors might act as bookmarks, maintaining the information and transmitting it to the next generation.

Results
We used the mouse globin gene clusters as a model system to examine the retention of active information on M-phase chromosomes and its contribution to the persistence of transcriptional competence of these gene clusters in murine erythroleukemia cells. In cells arrested in mitosis, the erythroid-specific activator NF-E2p45 remained associated with its binding sites on the globin gene loci, while the other major erythroid factor, GATA-1, was removed from chromosome. Moreover, despite mitotic chromatin condensation, the distant regulatory regions and promoters of transcriptionally competent globin gene loci are marked by a preserved histone code consisting in active histone modifications such as H3 acetylation, H3-K4 dimethylation and K79 dimethylation. Further analysis showed that other active genes are also locally marked by the preserved active histone code throughout mitotic inactivation of transcription.

Conclusion
Our results imply that certain kinds of specific protein factors and active histone modifications function as cellular memory markers for both competent and active genes during mitosis, and serve as a reactivated core for the resumption of transcription when the cells exit mitosis.
Mistletoe lectin is not the only cytotoxic component in fermented preparations of Viscum album from white fir (Abies pectinata)
Authors: Eggenschwiler Jenny , von Balthazar Leopold , Stritt Bianca , Pruntsch Doreen , Ramos Mac , Urech Konrad , Rist Lukas , Simões-Wüst A Paula , Viviani Angelika 
Published: May 2007

Abstract

Background
Preparations of mistletoe (Viscum album) are the form of cancer treatment that is most frequently used in the complementary medicine. Previous work has shown that these preparations are able to exert cytotoxic effects on carcinoma cells, the extent of which might be influenced by the host tree species and by the content of mistletoe lectin.

Methods
Using colorimetric assays, we have now compared the cytotoxic effects of Viscum album preparations (VAPs) obtained from mistletoe growing on oak (Quercus robur and Q. petraea, VAP-Qu), apple tree (Malus domestica,, VAP-M), pine (Pinus sylvestris, VAP-P) or white fir (Abies pectinata, VAP-A), on the in vitro growth of breast and bladder carcinoma cell lines. While MFM-223, KPL-1, MCF-7 and HCC-1937 were the breast carcinoma cell lines chosen, the panel of tested bladder carcinoma cells comprised the T-24, TCC-SUP, UM-UC-3 and J-82 cell lines.

Results
Each of the VAPs inhibited cell growth, but the extent of this inhibition differed with the preparation and with the cell line. The concentrations of VAP-Qu, VAP-M and VAP-A which led to a 50 % reduction of cell growth (IC50) varied between 0.6 and 0.03 mg/ml. Higher concentrations of VAP-P were required to obtain a comparable effect. Purified mistletoe lectin I (MLI) led to an inhibition of breast carcinoma cell growth at concentrations lower than those of VAPs, but the sensitivity towards purified MLI did not parallel that towards VAPs. Bladder carcinoma cells were in most cases more sensitive to VAPs treatment than breast carcinoma cells. The total mistletoe lectin content was very high in VAP-Qu (54 ng/mg extract), intermediate in VAP-M (25 ng/mg extract), and very low in VAP-P (1.3 ng/mg extract) and in VAP-A (1 ng/mg extract). As to be expected from the low content of mistletoe lectin, VAP-P led to relatively weak cytotoxic effects. Most remarkably, however, the lectin-poor VAP-A revealed a cytotoxic effect comparable to, or even stronger than, that of the lectin-rich VAP-Qu, on all tested bladder and breast carcinoma cell lines.

Conclusion
The results suggest the existence of cytotoxic components other than mistletoe lectin in VAP-A and reveal an unexpected potential of this preparation for the treatment of breast and bladder cancer.
Laparoscopic resection of a torted ovarian dermoid cyst
Authors: Williams Katie M , Bain Charles J , Kelly Michael D 
Published: May 2007

Abstract
Torsion or rupture of an ovarian cyst may present as an acute abdomen. A case is presented where the diagnosis was made at laparoscopy and laparoscopic resection was done. Controlled aspiration of the cyst contents allowed the cyst to be easily removed from the abdomen.
Prediction of death and prolonged mechanical ventilation in acute lung injury
Authors: Gajic Ognjen , Afessa Bekele , Thompson B Taylor , Frutos-Vivar Fernando , Malinchoc Michael , Rubenfeld Gordon D , Esteban André , Anzueto Antonio , Hubmayr Rolf D ,   the Second International Study of Mechanical Ventilation and ARDS-net Investigators
Published: May 2007

Abstract
Introduction
Prediction of death and prolonged mechanical ventilation is important in terms of projecting resource utilization and in establishing protocols for clinical studies of acute lung injury (ALI). We aimed to identify risk factors for a combined end-point of death and/or prolonged ventilator dependence and developed an ALI-specific prediction model.

Methods
In this retrospective analysis of three multicenter clinical studies, we identified predictors of death or ventilator dependence from variables prospectively recorded during the first three days of mechanical ventilation. After the prediction model was derived in an international cohort of patients with ALI, it was validated in two independent samples of patients enrolled in a clinical trial involving 17 academic centers and a North American population-based cohort.

Results
A combined end-point of death and/or ventilator dependence at 14 days or later occurred in 68% of patients in the international cohort, 60% of patients in the clinical trial, and 59% of patients in the population-based cohort. In the derivation cohort, a model based on age, oxygenation index on day 3, and cardiovascular failure on day 3 predicted death and/or ventilator dependence. The prediction model performed better in the clinical trial validation cohort (area under the receiver operating curve 0.81, 95% confidence interval 0.77 to 0.84) than in the population-based validation cohort (0.71, 95% confidence interval 0.65 to 0.76).

Conclusion
A model based on age and cardiopulmonary function three days after the intubation is able to predict, moderately well, a combined end-point of death and/or prolonged mechanical ventilation in patients with ALI.
Mass Spectral Determination of Fasting Tear Glucose Concentrations in Nondiabetic Volunteers
Authors: Baca Justin T , Taormina Christopher R , Feingold Eleanor , Finegold David N , Grabowski Joseph J , Asher Sanford A 
Published: May 2007

Abstract
Background: There is considerable disagreement regarding the concentration of glucose in tears and its relationship to the concentration in blood. Improved sampling and analysis methods may resolve these discrepancies and possibly provide a basis for in situ tear glucose sensors.
Methods: We used liquid chromatography (LC) with electrospray ionization mass spectrometry (ESI-MS) to determine glucose in 1-μL tear fluid samples obtained from 25 fasting study participants. Tear fluid was collected with microcapillaries and a slitlamp microscope.
Results: The median (range) of fasting tear glucose concentrations was 28 (7–161) μmol/L or 0.50 (0.13–2.90) mg/dL. The SD of tear glucose measurements for individuals varied linearly with the mean tear glucose concentration and was approximately half of the mean. We found no significant difference in tear glucose concentrations between contact lens users and nonusers (P = 0.715). We observed significant correlations between fasting blood and tear glucose concentrations (R = 0.50, P = 0.01).
Conclusions: Our tear fluid collection and analysis method enables reliable measurement of equilibrium, fasting tear glucose concentrations. These concentrations are lower than those previously reported for nondiabetic persons. Larger population studies are required to determine correlations between blood and tear glucose concentrations and to determine the utility of contact lens–based sensors for the monitoring of diabetes. Our methods are applicable for study of other tear fluid analytes and may prove useful for monitoring other disease states.
6-Thioguanine Nucleotide–Adapted Azathioprine Therapy Does Not Lead to Higher Remission Rates Than Standard Therapy in Chronic Active Crohn Disease: Results from a Randomized, Controlled, Open Trial
Authors: Reinshagen Max , Schütz Ekkehard , Armstrong Victor W , Behrens Christoph , von Tirpitz Christian , Stallmach Andreas , Herfarth Hans , Stein Jürgen , Bias Peter , Adler Guido , Shipkova Maria , Kruis Wolfgang , Oellerich Michael , von Ahsen Nicolas 
Published: May 2007

Abstract
Background: A prospective randomized trial in patients with Crohn disease studied whether 6-thioguanine nucleotide (6-TGN) concentration–adapted azathioprine (AZA) therapy is clinically superior to a standard dose of 2.5 mg/kg/day AZA.
Methods: After 2 weeks of standard therapy, patients (n = 71) were randomized into standard (n = 32) or adapted-dose (n = 25) groups; 14 patients dropped out before randomization. In the adapted group, the AZA dose was adjusted to maintain 6-TGN concentrations between 250 and 400 pmol/8 × 108 erythrocytes (Ery). Response criteria were the number of patients in remission after 16 weeks without steroids (primary) and remission after 24 weeks, frequency of side effects, and quality of life (secondary).
Results: After 16 weeks, 14 of 32 (43.8%) patients in the standard group vs 11 of 25 (44%) in the adapted group were in remission without steroids (intent-to-treat analysis). After 24 weeks, 43.8% vs 40% were in remission. No significant differences were found concerning quality of life, disease activity, 6-TGN concentrations, AZA dose, or dropouts due to side effects. Sixty-six patients had a wild-type thiopurine S-methyltransferase (TPMT) genotype, with TPMT activities of 8 to 20 nmol/(mL Ery × h). Five patients (dropouts after randomization) were heterozygous, with TPMT activities &lt;8 nmol/(mL Ery × h). 6-Methyl mercaptopurine (6-MMP) concentrations &gt;5700 pmol/8 × 108 Ery were not associated with hepatotoxicity.
Conclusion: Standard and adapted dosing with the provided dosing scheme led to identical 6-TGN concentrations and remission rates. Adapted dosing had no apparent clinical benefit for patients with TPMT activity between 8 and 20 nmol/(mL Ery × h). Additionally, 6-MMP monitoring had no predictive value for hepatotoxicity.
Nonvolatile Memory Elements Based on Organic Materials
Authors: Scott J. C. , Bozano L. D. 
Published: May 2007

AbstractMany organic electronic devices exhibit switching behavior, and have therefore been proposed as the basis for a nonvolatile memory (NVM) technology. This Review summarizes the materials that have been used in switching devices, and describes the variety of device behavior observed in their charge–voltage (capacitive) or current–voltage (resistive) response. A critical summary of the proposed charge‐transport mechanisms for resistive switching is given, focusing particularly on the role of filamentary conduction and of deliberately introduced or accidental nanoparticles. The reported device parameters (on–off ratio, on‐state current, switching time, retention time, cycling endurance, and rectification) are compared with those that would be necessary for a viable memory technology.