bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sprouty4 levels are increased under hypoxic conditions by enhanced mRNA stability and transcription
Authors: Haigl Barbara , Mayer Christoph-Erik , Siegwart Gerald , Sutterlüty Hedwig 
Published: May 2010

Abstract
Sprouty (Spry) proteins are well-known negative regulators of receptor tyrosine kinase-mediated signalling. Their expression is controlled by mitogens, implying a negative feedback loop. Correspondingly, the different members of the family fulfil important roles during organogenesis by adjustment of growth factor-induced processes. In addition, Spry4, one member of this protein family, has been shown to regulate angiogenesis by inhibiting vascular endothelial cell growth factor-induced extracellular signalling-regulated kinase (ERK) activation. Because oxygen is an important regulator of angiogenesis, we investigated Spry4 expression patterns under hypoxic conditions. Our data demonstrate that both hypoxia and desferrioxamine (DFO) treatment increased Spry4 expression. Following iron depletion, elevated Spry4 levels were detected in several cell types independent of tissue origin, presence of mitogens, cell differentiation and malignancy. Evaluation of the underlying regulative mechanisms revealed that augmented transcription and increased mRNA stability enhance mRNA levels of Spry4 in response to DFO. This study unveils a growth factor-independent regulation mechanism of Spry4 expression. Because increased Spry4 levels are accompanied by disappearing ERK phosphorylation, Spry4 might be involved in the timely restriction of MAPK signals under hypoxic conditions, similar to its role in mitogen-regulated processes. However, the functional significance of the observed upregulation of Spry4 during iron depletion remains to be clarified.
Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.
Authors: Rapala-Kozik Maria , Karkowska-Kuleta Justyna , Ryzanowska Agnieszka , Golda Anna , Barbasz Anna , Faussner Alexander , Kozik Andrzej 
Published: May 2010

AbstractThe secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to be activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases ofCandidaspp. yeasts, the major fungal pathogens of humans. Of severalCandidaspecies studied,C. parapsilosisandC. albicansin their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases ofCandidaspp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism.
Molecular contortionism – on the physical limits of serpin ‘loop-sheet’ polymers
Authors: Huntington James A. , Whisstock James C. 
Published: May 2010

AbstractMembers of the serpin (serineproteaseinhibitor) superfamily fold into a metastable conformation that is crucial for proper function. As a consequence, serpins are susceptible to mutations that cause misfolding and the intracellular accumulation of pathogenic polymers. The mechanism of serpin polymerisation remains to be resolved, however, over the past two decades the ‘loop-sheet’ hypothesis has gained wide acceptance. In this mechanism the reactive centre loop of one serpin monomer inserts into the β-sheet A of another (in trans), in a manner similar to what is seen for reactive centre loop-cleaved and latent conformations (in cis). The hypothesis has been refined in response to certain experimental data, but it has proved difficult to assess the various propositions without creating molecular models. Here we evaluate the loop-sheet mechanism by creating models of pentamers of the archetypal serpin α1-antitrypsin. We conclude that an inescapable consequence of the loop-sheet mechanism is polymer compaction and rigidity, properties that are inconsistent with the ‘beads-on-a-string’ morphology of polymers obtained from human tissue. The recent crystal structure of a domain-swapped serpin dimer suggests an alternative mechanism that is consistent with known polymer properties, including the requirement of partial unfolding to induce polymer formationin vitro, and polymerisation from a folding intermediatein vivo.
Proteases in lymphocyte killer function: redundancy, polymorphism and questions remaining
Authors: Sutton Vivien R. , Trapani Joseph A. 
Published: May 2010

AbstractProteases of the serine and cysteine protease families are involved in many processes crucial to the lytic functions of cytotoxic T lymphocytes and natural killer cells. In this study we describe those functions and attempt to place them in the pathophysiological context of defence to pathogen invasion. In particular, we stress that the co-evolution of pathogens with the immune systems of higher organisms over evolutionary time has ensured that redundancy, flexibility and polymorphism of the proteases can be identified, both within the protease repertoire of a given species, and by comparing orthologous protease functions across species.
Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates
Authors: Mariuzza Roy A. , Velikovsky C. Alejandro , Deng Lu , Xu Gang , Pancer Zeev 
Published: May 2010

Abstract
Adaptive immunity in jawless vertebrates is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Whereas antibodies and T cell receptors (TCRs) are composed of immunoglobulin (Ig) domains, the variable lymphocyte receptors (VLRs) of jawless fish consist of leucine-rich repeat (LRR) modules. As with antibodies and TCRs, VLRs are assembled by DNA recombination in a process that generates a vast repertoire of receptors. VLRs recognize as diverse an array of particulate and soluble antigens as Ig-based antibodies, and do so with similar affinity and specificity. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens have shown that these LRR-based receptors use nearly all their concave surface to bind ligands, in addition to a highly variable loop in their C-terminal LRR capping module. This structural information, combined with a comprehensive analysis of VLR sequences, has revealed an almost perfect match between antigen-contacting positions and positions with highest sequence diversity. The independent evolution approximately 500 million years ago of LRR-based and Ig-based receptors of comparable diversity and antigen-binding properties provides evidence for the survival value of adaptive immunity in vertebrates.
Small-angle X-ray and neutron scattering as a tool for structural systems biology
Authors: Svergun Dmitri I. 
Published: May 2010

Abstract
Small-angle scattering (SAS) of X-rays and neutrons reveals low-resolution structures of biological macromolecules in solution. With the recent experimental and methodological advances, SAS became a unique tool for characterising biological systems. The method covers an extremely broad range of molecule sizes (from a few kDa to hundreds of MDa) and experimental conditions (temperature, pH, salinity, ligand addition, etc.), which is of primary importance for a systemic approach in structural biology. The method provides unique information about the overall structure and conformational changes of native individual proteins, functional complexes, flexible macromolecules and hierarchical systems. New developments in small-angle X-ray and neutron scattering studies of biological macromolecules in solution are briefly reviewed, with a special emphasis on technical and methodological approaches useful for structural systems biology. Possibilities of synergistic use of the method with other techniques are considered.
Urine particle evaluation: a comparison between the UF-1000i and quantitative microscopy
Authors: Manoni Fabio , Tinello Agostino , Fornasiero Lucia , Hoffer Paolo , Temporin Valeria , Valverde Sara , Gessoni Gianluca 
Published: May 2010

Abstract

Background: The study of urine particles plays a key role in the diagnosis of kidney diseases. In this study, the authors evaluated the correlation between the UF-1000i and quantitative manual microscopy.

Methods: A total of 214 untreated urine samples were studied using the Sysmex UF-1000i and compared with results obtained from quantitative manual microscopy using the Fuchs-Rosenthal counting chamber.

Results: Using Pearson statistics, we observed satisfactory correlation between the UF-1000i and quantitative microscopy: for red blood cells (RBCs) r was 0.98, for white blood cells (WBCs) r was 1.00, for epithelial cells (EC) r was 0.96, and for casts r was 0.69. Using linear regression statistics, we also observed satisfactory correlation between the UF-1000i and quantitative microscopy: for RBCs R2 was 0.95, for WBCs R2 was 0.99, for EC R2 was 0.92, and for casts R2 was 0.48.

Conclusions: In our experience, automated urine particle analysis performed using the Sysmex UF-1000i analyzer is sufficiently precise and improves the workflow in a routine laboratory. Precision was satisfactory and concordance with the reference method is good for RBC, WBC and EC; for casts microscopic observation is required for flagged samples to discriminate hyaline from pathologic casts.
Clin Chem Lab Med 2010;48:1107–11.
Non-invasive fetal RHD genotyping in the first trimester of pregnancy
Authors: Cardo Leyre , García Belén Prieto , Alvarez Francisco V. 
Published: May 2010

Abstract

Background: Hemolytic disease of the fetus and newborn (HDN) is caused primarily by feto-maternal RhD incompatibility. Although all RhD negative pregnant women undergo routine antenatal RhD prophylaxis at 28 weeks of gestation, and following delivery if the newborn is RhD positive, HDN has not been eradicated. Here, we investigated fetal Rhesus D (RHD) genotype in maternal plasma during the first trimester of pregnancy in our area.

Methods: Plasma samples were obtained from 111 RhD negative pregnant women, between 9 and 13 weeks of gestation. DNA from maternal plasma containing cell-free fetal DNA (cffDNA) was analyzed by quantitative PCR (qPCR) to detect RHD exons 5 and 7. A β-globin (HBB) sequence was quantified to estimate total DNA concentration. qPCR results were compared with newborn RhD determined in cord blood serum. The influence of several gestational parameters on DNA concentration was also analyzed.

Results: The specificity and sensitivity of the assay was 93% and 100%, respectively, with 97% diagnostic accuracy. Cell-free DNA concentrations during the first trimester of pregnancy were not affected by the gestational parameters studied (free-β fraction of human chorionic gonadotropin and pregnancy-associated plasma protein A concentrations, fetal sex, materno-fetal ABO blood group incompatibility, maternal weight and gestational age).

Conclusions: Non-invasive fetal RHD genotyping during the first trimester of pregnancy can be determined with a high specificity, thus representing a valuable tool for improving the management of RhD negative pregnant women. As a high percentage of pregnant women participate in the routine first trimester combined screening program for aneuploidies, the fetal RHD study could be of immediate implementation, since the same blood collection could be used.
Clin Chem Lab Med 2010;48:1121–6.
Homocysteine in small-for-gestational age and appropriate-for-gestational age preterm neonates from mothers receiving folic acid supplementation
Authors: Gomes Thushari S. , Lindner Ulrike , Tennekoon Kamani H. , Karandagoda Wimal , Gortner Ludwig , Obeid Rima 
Published: May 2010

Abstract

Background: Prematurity and small-for-gestational age (SGA) neonates are at risk for postnatal complications. Concentrations of total homocysteine (tHcy) might be related to neonatal outcome. We hypothesized that concentrations of tHcy are not related to growth restriction in neonates from mothers receiving 5 mg/day folic acid. We studied a total of 133 preterm neonates from normotensive mothers; SGA (n=96) and appropriate-for-gestational age (AGA, n=37).

Methods: Concentrations of tHcy, folate and vitamin B12 were measured in venous umbilical cord plasma.

Results: AGA preterm neonates had higher mean birth weight (BW) compared to SGA preterms (2472 g vs. 2007 g; p<0.001) of comparable mean gestational age (GA) (35.1 vs. 35.7 weeks; p=0.059). Concentrations of tHcy (4.86 vs. 4.95 μmol/L), folate (63.3 vs. 55.7 nmol/L), and vitamin B12 (409 vs. 394 pmol/L) were not significantly different between the groups. GA was a strong positive predictor, BW was a significant negative predictor of cord plasma folate. Vitamin B12 concentration was a significant negative predictor of cord tHcy.

Conclusions: Concentrations of tHcy did not differ between SGA and AGA preterm neonates born to mothers supplemented with folic acid. This finding argues against a causal role for folate deficiency or increased tHcy in growth restriction.
Clin Chem Lab Med 2010;48:1157–61.
Blood cell and iron status analytes of preterm and full-term infants from 20 weeks onwards during the first year of life
Authors: Takala Timo I. , Mäkelä Enni , Suominen Pauli , Matomäki Jaakko , Lapinleimu Helena , Lehtonen Liisa , Rajamäki Allan , Irjala Kerttu , Lähteenmäki Päivi M. 
Published: May 2010

AbstractBackground:The goal of this study was to evaluate the dynamics of blood cell and iron status laboratory analytes in preterm and full-term infants during the first year of life.Methods:This was a prospective study of 100 preterm and 50 full-term infants. Preterm infants received iron supplementation beginning at 3 weeks of age. Laboratory tests were serially analyzed up to 12 months of corrected age.Results:Estimated means and the 95% reference intervals (RIs) from 20 weeks of age and onwards are presented separately for preterm and full-term infants. At the age of 20 weeks, mean hemoglobin (Hb) in preterm infants was lower than mean Hb in full-term infants, but this difference changed during follow-up. Ferritin concentrations were initially lower in preterm infants, but decreased to similar levels in both groups. Estimated mean values for transferrin receptor and reticulocyte Hb content were quite stable between the ages of 20 and 55 weeks in both groups.Conclusions:Our study suggests that the same RIs for preterm and full-term infants can be used from the age of 20 or 30 weeks onwards, depending on the analyte. The RIs will help physicians detect iron deficiency or other problems of erythropoiesis in infants.Clin Chem Lab Med 2010;48:1295–301.
Changes in Functional Performance Measures in Adults Undergoing Chemoradiation for Primary Malignant Glioma: A Feasibility Study
Authors: Jones Lee W. , Mourtzakis Marina , Peters Katherine B. , Friedman Allan H. , West Miranda J. , Mabe Stephanie K. , Kraus William E. , Friedman Henry S. , Reardon David A. 
Published: May 2010

Abstract

Purpose.
To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients.

Methods.
Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO2peak) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy–Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery.

Results.
Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO2peak and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values &lt; .05).

Conclusions.
Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.
Plasma Soluble VEGFR-1 Is a Potential Dual Biomarker of Response and Toxicity for Bevacizumab with Chemoradiation in Locally Advanced Rectal Cancer
Authors: Duda Dan G. , Willett Christopher G. , Ancukiewicz Marek , Tomaso Emmanuelle , Shah Mira , Czito Brian G. , Bentley Rex , Poleski Martin , Lauwers Gregory Y. , Carroll Madeline , Tyler Douglas , Mantyh Christopher , Shellito Paul , Clark Jeffrey W. , Jain Rakesh K. 
Published: May 2010

Abstract
We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR-1), and sVEGFR-2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002–2008 with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR-1—an endogenous blocker of VEGF and PlGF, and a factor linked with “vascular normalization”—was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR-1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.
The Immediate Reduction in Low Back Pain Intensity Following Lumbar Joint Mobilization and Prone Press-ups Is Associated With Increased Diffusion of Water in the L5-S1 Intervertebral Disc
Authors: Beattie Paul F. , Arnot Cathy F , Donley Jonathan W. , Noda Harmony , Bailey Lane 
Published: May 2010

Study Design Single-group, prospective repeated-measures design. Objectives To determine differences in the changes of diffusion of water in the L5-S1 intervertebral disc between subjects with nonspecific low back pain (LBP) who reported an immediate reduction in pain intensity of 2 or greater on an 11-point (0–10) numeric rating scale after a 10-minute session of lumbar joint mobilization, followed by prone press-up exercises, compared to those who did not report an immediate reduction in pain intensity of 2 or greater on the pain scale. Background Combining lumbar joint mobilization and prone press-up exercises is a common intervention for patients with LBP; however, there is conflicting evidence regarding the effectiveness and efficacy of this approach. Increased knowledge of the physiologic effects of the combined use of these treatments, and the relationship to pain reports, can lead to refinement of their clinical application. Methods Twenty adults, aged 22 to 54, participated in this study. All subjects reported LBP of at least 2 on an 11-point (0–10) verbally administered numeric rating scale at the time of enrollment in the study and were classified as being candidates for the combination of joint mobilization and prone press-ups. Subjects underwent T2- and diffusion-weighted lumbar magnetic resonance imaging scans before and immediately after receiving a 10-minute session of lumbar pressures in a posterior-to-anterior direction and prone press-up exercises. Subjects who reported a decrease in current pain intensity of 2 or greater immediately following treatment were classified as immediate responders, while the remainder were classified as not-immediate responders. The apparent diffusion coefficient, representing the diffusion of water in the nucleus pulposis, was calculated from the midsagittal diffusion-weighted images. Results Following treatment, immediate responders (n = 10) had a mean increase in the apparent diffusion coefficient in the middle portion of the L5-S1 intervertebral disc of 4.2% compared to a mean decrease of 1.6% for the not-immediate responders (P<.005). Conclusion In a group of subjects with LBP, who were classified as being candidates for extension-based treatment, the report of an immediate reduction in pain intensity of 2/10 of greater after a treatment of posterior-to-anterior-directed pressures, followed by prone press-up exercises, was associated with an increase in diffusion of water in the nuclear region of the L5-S1 intervertebral disc. Subjects who did not report a pain reduction of at least 2/10 did not have a change in diffusion. J Orthop Sports Phys Ther 2010;40(5)256–264. doi:102519/jospt.2010.3284