bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients
Authors: Petitjean Gaël , Al Tabaa Yassine , Tuaillon Edouard , Mettling Clement , Baillat Vincent , Reynes Jacques , Segondy Michel , Vendrell Jean Pierre 
Published: August 2007

Abstract

Background
The presence of HIV-1 preintegration reservoir was assessed in an in vitro experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART).

Results
In resting CD4+ T lymphocytes latently infected in vitro with HIV-1, we demonstrated that the polyclonal activation induced a HIV-1 replication, which could be prevented by the use of an HIV-1 integrase inhibitor. We also showed that this reservoir was labile since the rescuable HIV-1-antigens production from unintegrated HIV-1 genomes declined over time. These data confirm that our experimental approach allows the characterization of a functional unintegrated HIV-1 reservoir. We then explored the preintegration reservoir in HIV-1-infected patients. This reservoir was detected in 11 of 12 untreated patients, in 4 of 10 sustained responders to HAART, and in one incomplete responder. This reservoir was also inducible, labile, and anti-HIV-1 integrase drug inhibited its induction. Finally, this reservoir was associated with the presence of spontaneous HIV-1 antigens producing CD4+ T cells in blood from 3 of 3 untreated patients and 2 of 2 sustained responders to HAART harboring a preintegration reservoir.

Conclusion
This preintegration phase of HIV-1 latency could be a consequence of the ongoing viral replication in untreated patients and of a residual viral replication in treated patients.
Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques (Macaca fascicularis)
Authors: Hammamieh Rasha , Barmada Mohsen , Ludwig George , Peel Sheila , Koterski Nick , Jett Marti 
Published: August 2007

Abstract

Background
Lymphocytes provide invaluable whistle blowers of changes due to infections. We use the information registered by these cells using their mRNAs as they encounter the pathogen to develop patterns of expression that correspond to that specific pathogen.
Venezuelan equine encephalitis (VEE) is a mosquito-borne viral disease characterized by fever and one or more of the following: severe headache, back pain, myalgias, prostration, chills, nausea, vomiting, weakness and other flu-like symptoms.
Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.

Results
We have been carrying out gene expression analysis of PBMC exposed to VEEV to extract signatures and diagnostic markers of early exposure to be used in non invasive blood analysis methods.
In this study, we used high throughput gene expression analysis to identify markers of early and late exposures to VEEV in vivo in Cynomolgus macaques (Macaca fascicularis). We carried out cDNA microarrays and real time PCR on blood samples obtained from the NHP model resulting in a panel of host genes that are altered in response to VEEV.

Conclusion
Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.
Mitotic regulation by NIMA-related kinases
Authors: O'Regan Laura , Blot Joelle , Fry Andrew M 
Published: August 2007

Abstract
The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets.
Distribution patterns of small-molecule ligands in the protein universe and implications for origin of life and drug discovery
Authors: Ji Hong-Fang , Kong De-Xin , Shen Liang , Chen Ling-Ling , Ma Bin-Guang , Zhang Hong-Yu 
Published: August 2007

AbstractBackgroundExtant life depends greatly on the binding of small molecules (such as ligands) with macromolecules (such as proteins), and one ligand can bind multiple proteins. However, little is known about the global patterns of ligand-protein mapping.ResultsBy examining 2,186 well-defined small-molecule ligands and thousands of protein domains derived from a database of druggable binding sites, we show that a few ligands bind tens of protein domains or folds, whereas most ligands bind only one, which indicates that ligand-protein mapping follows a power law. Through assigning the protein-binding orders (early or late) for bio-ligands, we demonstrate that the preferential attachment principle still holds for the power-law relation between ligands and proteins. We also found that polar molecular surface area, H-bond acceptor counts, H-bond donor counts and partition coefficient are potential factors to discriminate ligands from ordinary molecules and to differentiate super ligands (shared by three or more folds) from others.ConclusionThese findings have significant implications for evolution and drug discovery. First, the chronology of ligand-protein binding can be inferred by the power-law feature of ligand-protein mapping. Some nucleotide-containing ligands, such as ATP, ADP, GDP, NAD, FAD, dihydro-nicotinamide-adenine-dinucleotide phosphate (NDP), nicotinamide-adenine-dinucleotide phosphate (NAP), flavin mononucleotide (FMN) and AMP, are found to be the earliest cofactors bound to proteins, agreeing with the current understanding of evolutionary history. Second, the finding that about 30% of ligands are shared by two or more domains will help with drug discovery, such as in finding new functions from old drugs, developing promiscuous drugs and depending more on natural products.
Interactions of TANGO and leukocyte integrin CD11c/CD18 regulate the migration of human monocytes
Authors: Arndt Stephanie , Melle Christian , Mondal Krishna , Klein Gerd , Von Eggeling Ferdinand , Bosserhoff Anja-Katrin 
Published: August 2007

AbstractThe TANGO gene was originally identified as a new member of the MIA gene family. It codes for a protein of yet unknown function. TANGO revealed a very broad expression pattern in contrast to the highly restricted expression pattern determined for the other family members. The only cells lacking TANGO expression are cells of the hematopoietic system. One of the major differences between mature hematopoietic cells and other tissue cells is the lack of adhesion until these cells leave the bloodstream. In this study, we observed that TANGO expression was induced after adhesion of human monocytic cells to substrate. To understand the mechanism of TANGO function during monocyte adhesion we isolated interacting proteins and found an interaction between TANGO and the leukocyte-specific integrin CD11c. In functional assays, we observed reduced attachment of human monocytic cells to fibrinogen, ICAM-1 and to human microvascular endothelial cells (HMECs) after stimulation with recombinant TANGO protein. Additionally, the migrating capacity of premonocytic cells through fibrinogen or HMECs was increased after stimulation of these cells with recombinant TANGO. Therefore, we suggest that TANGO reduced the attachment to fibrinogen or other cell adhesion molecules. As TANGO does not compete for CD11c ligand binding directly, we hypothesize TANGO function by modulation of integrin activity. Taken together, the results from this study present TANGO as a novel ligand for CD11c, regulating migratory processes of hematopoietic cells.
A SELDI-TOF MS study of the genetic and post-translational molecular heterogeneity of eosinophil cationic protein
Authors: Eriksson Jenny , Woschnagg Charlotte , Fernvik Eva , Venge Per 
Published: August 2007

AbstractEosinophil cationic protein (ECP), a secretory protein of the eosinophil granulocyte, is a basic and highly heterogeneous protein. This heterogeneity is dependent on polymorphisms in the ECP gene and post-translational modifications, and it affects the functional properties of the protein in terms of cytotoxicity. The aim of this study was to further investigate the molecular heterogeneity, hence, an affinity capture assay based on an antigen-antibody interaction with the surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) technique was developed. Of three monoclonal antibodies tested, that is, EG2, 614, and 652, the 614 mab was chosen for the experiments. ECP heterogeneity of single individuals was studied in extracts of purified blood eosinophils, and the presence of ∼5 major molecular species was demonstrated in each subject. ECP from subjects with different ECP 434(G&gt;C) genotypes (arg97thr) showed mass differences corresponding to the amino acid shift from arginine to threonine. ECP purified from pooled leukocytes of large numbers of healthy blood donors demonstrated an extensive mass heterogeneity with ∼10 major molecular species. By the use of a variety of glucosidases it was shown that this heterogeneity was mainly due to N-linked oligosaccharides on which sialic acid, galactose, and acetylglucosamine was positioned. We conclude that the SELDI-TOF MS technique using specific monoclonal antibodies is a convenient and versatile tool; by means of this technique, we could detect both genetic and post-translational causes of the molecular heterogeneity of the eosinophil cationic protein.
Insulin Resistance Is Unrelated to Circulating Retinol Binding Protein and Protein C Inhibitor
Authors: Promintzer Miriam , Krebs Michael , Todoric Jelena , Luger Anton , Bischof Martin Georg , Nowotny Peter , Wagner Oswald , Esterbauer Harald , Anderwald Christian 
Published: August 2007

AbstractContext: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant.Objective: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen.Design and Setting: This was a clinical study.Patients: Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 ± 1.9 yr, body mass index 26 ± 1 kg/m2) and low (IR; n = 20, 14 females, six males, aged 45.5 ± 1.7 yr, body mass index 28 ± 1 kg/m2) insulin-stimulated glucose-disposal (M) participated in this study.Main Outcome Measures: M was measured by 2-h hyperinsulinemic (40 mU·min−1·m−2)-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting.Results: M (80–120 min) was higher in IS (10.9 ± 0.6 mg·min−1·kg−1) than IR (4.0 ± 0.2; P &lt; 10−12). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 ± 0.3; IR: 4.6 ± 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 ± 0.5, IR 8.3 ± 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P &lt; 0.001), prealbumin (r = 0.63, P &lt; 0.0001), and vitamin A (r = 0.75, P &lt; 10−6).Conclusions: Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport.
Relationships of Urinary Adrenal Steroids at Age 8 Years with Birth Weight, Postnatal Growth, Blood Pressure, and Glucose Metabolism
Authors: Honour John W. , Jones Richard , Leary Sam , Golding Jean , Ong Ken K. , Dunger David B. 
Published: August 2007

Abstract
Introduction: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids.
Methods: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2–8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5α-androgen reduction of androgens and cortisol metabolites and 11β-hydroxy steroid dehydrogenase activity were calculated.
Results: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5α-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11β-hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex.
Conclusions: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth.
Exon Splice Enhancer Mutation (GH-E32A) Causes Autosomal Dominant Growth Hormone Deficiency
Authors: Petkovic Vibor , Lochmatter Didier , Turton James , Clayton Peter E. , Trainer Peter J. , Dattani Mehul T. , Eblé Andrée , Robinson Iain C. , Flück Christa E. , Mullis Primus E. 
Published: August 2007

AbstractContext and Objective: Alteration of exon splice enhancers (ESE) may cause autosomal dominant GH deficiency (IGHD II). Disruption analysis of a (GAA) (n) ESE motif within exon 3 by introducing single-base mutations has shown that single nucleotide mutations within ESE1 affect pre-mRNA splicing.Design, Setting, and Patients: Confirming the laboratory-derived data, a heterozygous splice enhancer mutation in exon 3 (exon 3 + 2 A→C) coding for GH-E32A mutation of the GH-1 gene was found in two independent pedigrees, causing familial IGHD II. Because different ESE mutations have a variable impact on splicing of exon 3 of GH and therefore on the expression of the 17.5-kDa GH mutant form, the GH-E32A was studied at the cellular level.Interventions and Results: The splicing of GH-E32A, assessed at the protein level, produced significantly increased amounts of 17.5-kDa GH isoform (55% of total GH protein) when compared with the wt-GH. AtT-20 cells coexpressing both wt-GH and GH-E32A presented a significant reduction in cell proliferation as well as GH production after forskolin stimulation when compared with the cells expressing wt-GH. These results were complemented with confocal microscopy analysis, which revealed a significant reduction of the GH-E32A-derived isoform colocalized with secretory granules, compared with wt-GH.Conclusion: GH-E32A mutation found within ESE1 weakens recognition of exon 3 directly, and therefore, an increased production of the exon 3-skipped 17.5-kDa GH isoform in relation to the 22-kDa, wt-GH isoform was found. The GH-E32A mutant altered stimulated GH production as well as cell proliferation, causing IGHD II.
Transcriptional Inhibition of Oxytocin Receptor Expression in Human Myometrial Cells by Melatonin Involves Protein Kinase C Signaling
Authors: Sharkey James , Olcese James 
Published: August 2007

Abstract
Context: Our laboratory recently characterized the expression of the melatonin receptors in the human myometrium and showed that the expression of these receptors is suppressed during late pregnancy.
Objective: In an effort to understand better the significance of melatonin in the human myometrium, we explored the mechanisms through which this hormone influences the expression of the oxytocin receptor in vitro.
Design: The stable melatonin analog iodomelatonin was presented to cultured telomerase-immortalized myometrial cells of the human telomerase reverse transcriptase line under physiological doses and durations. Pharmacological inhibitors of melatonin binding, gene transcription, phospholipase C, and protein kinase C signaling were used to define the mechanism of melatonin action.
Results: Our results reveal that melatonin significantly inhibits oxytocin receptor mRNA expression primarily via the melatonin 2 receptor. The melatonin-dependent decrease in oxytocin receptor transcripts involves suppression of gene transcription rather than enhanced rates of transcript degradation. Melatonin effects were abolished by pretreating the cells with the phospholipase C inhibitor U73122 or the protein kinase C inhibitor C1.
Conclusions: Melatonin, like oxytocin, can negatively regulate oxytocin receptor transcription in human myometrial cells via modulation of protein kinase C signaling. This is consistent with the hypothesis that the reduced melatonin receptor expression during late pregnancy, which occurs at a time when oxytocin receptors are up-regulated, may be physiologically important for the subsequent timing of labor.
Estradiol Fatty Acid Esters in Adipose Tissue and Serum of Pregnant and Pre- and Postmenopausal Women
Authors: Badeau Maija , Vihma Veera , Mikkola Tomi S. , Tiitinen Aila , Tikkanen Matti J. 
Published: August 2007

AbstractContext: The 17β-estradiol fatty acid esters are hormone derivatives with long-lasting estrogenic effect. They are transported in serum lipoproteins and thought to be sequestered in adipose tissue.Objective: Our objective was to determine the 17β-estradiol fatty acid ester concentrations in serum and adipose tissue in women of various hormonal states.Design: After several chromatographic steps separating esterified from free estradiol, time-resolved fluoroimmunoassay was used as a quantifying tool.Participants: Samples were obtained from pregnant women undergoing cesarean section (n = 13), or premenopausal (n = 8) and postmenopausal women (n = 6) during gynecological surgery.Main Outcome Measures: 17β-Estradiol and 17β-estradiol fatty acid ester concentrations in serum, and visceral and sc adipose tissue were examined.Results: The ratio of esterified to free estradiol in plasma increased with decreasing estradiol level from 0.5% in pregnant, to 15% in premenopausal and 110% in postmenopausal women. Estradiol esters constituted about 10% of the free estradiol present in adipose tissue in pregnancy. In nonpregnant women, most of the adipose tissue estradiol was in esterified form, the median ester to free ratio being elevated to 150–490%. After menopause, the overwhelming majority of estradiol in both free and esterified form was present in adipose tissue.Conclusions: The overall higher ester to free estradiol ratio in adipose tissue than in serum indicates active esterification capacity in adipose tissue. The predominance of esterified and free estradiol in postmenopausal adipose tissue compared with serum suggests in situ production and storage. Whether the estradiol esters have an independent physiological role in adipose tissue remains to be clarified.
A Detection Method for Oscillating Chemical Reactions by Resonance Light Scattering Technique
Authors: Yan Ping , Li Yuan Fang , Huang Cheng Zhi 
Published: August 2007

Abstract
In this contribution, a resonance light-scattering (RLS) detection method is proposed for the measurements of oscillating reaction with H2O2–KSCN–CuSO4–NaOH close system as an example. The seasonal change of oscillating chemical reactions concerning the particle size is examined, and the qualitative analytical information could be obtained from this straightforward and expeditious approach.
Efficient Conversion of Carbon Dioxide to Methanol Using Copper Catalyst by a New Low-temperature Hydrogenation Process
Authors: Liu Yong , Zhang Yi , Wang Tiejun , Tsubaki Noritatsu 
Published: August 2007

Abstract
By employing a new low-temperature process for methanol synthesis, high activity of methanol production from CO2 hydrogenation was achieved at 443 K and 5 MPa in a slurry-phase reactor over the copper catalysts prepared by an oxalate-gel coprecipitation (OC) method.
Association of classical and related inflammatory markers with high-sensitivity C-reactive protein in healthy individuals: results from the Stanislas cohort
Authors: Berrahmoune Hind , Herbeth Bernard , Lamont John V. , Lambert Daniel , Blankenberg Stefan , Tiret Laurence , FitzGerald Peter S. , Siest Gérard , Visvikis-Siest Sophie 
Published: August 2007

AbstractClin Chem Lab Med 2007;45:1339–46.
High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction
Authors: Elmas Elif , Lang Siegfried , Erik Dempfle Carl , Kälsch Thorsten , Hannak Dieter , Sueselbeck Tim , Wolpert Christian , Borggrefe Martin , Brueckmann Martina 
Published: August 2007

AbstractClin Chem Lab Med 2007;45:1360–5.
Frequency Control of Motor Patterning by Negative Sensory Feedback
Authors: Ausborn Jessica , Stein Wolfgang , Wolf Harald 
Published: August 2007

The sensory system plays a key role in the generation of behavior by providing the nervous system with information about the environment and feedback about body movements such that motor output can continuously be adapted to changing circumstances. Although the effects of sensory organs on nervous system function have been demonstrated in many systems, the impact of sensory activity has rarely been studied in conditions in which motor output and sensory activity can interact as they do in behaving animals. In such situations, emergent properties may surface and govern the characteristics of the motor system.We studied the dynamics of sensorimotor interaction with a combination of electrophysiological experiments and computational modeling in the locust flight pattern generator, including its sensory components. The locust flight motor output is produced by a central pattern generator that interacts with phasic sensory feedback from the tegula, a proprioceptor that signals downstroke movement of the wing. We modeled the flight control system, and we tested the model predictions by replacing tegula feedback in the animal with artificial feedback through computer-controlled electric stimulation of the appropriate sensory nerves.With reference to the cycle frequency in the locust flight rhythm, our results show that motor patterns can be regulated via the variation of sensory feedback loops. In closed-loop conditions, tegula feedback strength determines cycle frequency in the model and the biological preparation such that stronger feedback results in lower frequencies. This regulatory mechanism appears to be a general emergent property of negative feedback systems.