bluuebunny/crossref_metadata_2025 huggingface dataset:
Herpesvirus prevalence and viral load in healthy blood donors by quantitative real‐time polymerase chain reaction
Authors: Hudnall S. David , Chen Tiansheng , Allison Paul , Tyring Stephen K. , Heath Ashley
Published: April 2008

BACKGROUND: After primary infection, human herpesviruses (HHVs) maintain long‐term latent persistence, often punctuated years later by sporadic episodes of symptomatic lytic activation. Also, blood‐borne herpesvirus from healthy persistently infected blood donors can lead to active primary infection of immunocompromised transfusion recipients.

STUDY DESIGN AND METHODS: Utilizing a set of newly developed real‐time polymerase chain reaction assays for detection and quantification of all eight human herpesviruses, the prevalence and viral DNA load of white cell–enriched blood from 100 randomly selected blood donors from the southeast Texas region are reported.

RESULTS: Herpes simplex viruses 1 and 2 (HSV‐1 and HSV‐2), varicella‐zoster virus (VZV), and HHV‐8 DNA were not detected in any donor sample. In contrast, Epstein‐Barr virus (EBV) (72%) and HHV‐7 (65%) were commonly detected, HHV‐6 (30%) was often detected (Type B only), and cytomegalovirus (CMV; 1%) was rarely detected. Median viral loads of positive samples (per milliliter of blood) ranged from 4278 for HHV‐6 to less than 46 for EBV.

CONCLUSIONS: These results suggest that the potential for transfusion‐mediated transmission of herpesviruses from healthy adult blood donors is high for EBV and HHV‐7; moderately high for HHV‐6; uncommon for CMV; and rare for HSV‐1, HSV‐2, VZV, and HHV‐8. Perhaps the most remarkable finding in this study was the detection of a single donor sample with greater than 6.1 × 107 HHV‐6 Type B genome equivalents per mL blood. Given that this extraordinarily high level of HHV‐6 DNA was obtained from a healthy adult blood donor, this phenomenon is likely unrelated to active infection or immunodeficiency.
Detailed immunophenotypic characterization of different major and minor subsets of peripheral blood cells in patients with paroxysmal nocturnal hemoglobinuria
Authors: Hernández‐Campo Pilar M. , Almeida Julia , Acevedo María J. , Sánchez María L. , Alberca Ignacio , Vidriales Belén , Martínez Elvira , Romero Juan R. , Orfao Alberto
Published: April 2008

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a deficient expression of glycosylphosphatidylinositol‐anchored proteins (GPI‐APs), due to somatic mutations of the phosphatidylinositolglycan complementation Class A (PIG‐A) gene.

STUDY DESIGN AND METHODS: In this study, the expression of a high number of GPI‐APs on different subsets of peripheral blood (PB) cells from 14 PNH patients and their potential association with underlying genetic abnormalities has been analyzed.

RESULTS: This study confirms the existence of variable patterns of expression of different GPI‐APs on both major and minor PB‐cell subsets from PNH patients. The size of the PNH clone within PB neutrophils and monocytes was systematically higher than that of other cell populations. Genetic changes were detected in the PIG‐A gene in 5 of 13 cases analyzed. Interestingly, the reactivity for many GPI‐APs was significantly higher on different subsets of normal PB cells from PNH patients than those observed on healthy volunteers.

CONCLUSION: The best combination of markers for the diagnostic screening of PNH would include evaluation of CD14 on monocytes and of CD16 on neutrophils, although further analysis of CD55 and CD59 expression may contain additional clinically useful information. Clear association between the genetic changes detected in the PIG‐A gene in 5 of 13 cases analyzed, and the phenotypic profile of PNH cells has not been found. Additionally, an abnormally higher expression of several GPI‐APs among normal residual cells from PNH patients in comparison to healthy donors was observed, suggesting that factors other than the PIG‐A mutation could determine the phenotypic profile of PB cells in PNH.
An algorithm based on peripheral CD34+ cells and hemoglobin concentration provides a better optimization of apheresis than the application of a fixed CD34 threshold
Authors: Delamain Márcia T. , Marques José F.C. , De Souza Carmino A. , Lorand‐Metze Irene , Metze Konradin
Published: April 2008

BACKGROUND: Optimization of peripheral blood stem cell (PBSC) collection for autologous bone marrow transplantation is necessary for a good standard of care and cost‐effectiveness. An algorithm was validated for prediction of the day of maximum peripheral CD34+ cell concentration after mobilization chemotherapy (DayCD34peak).

STUDY DESIGN AND METHODS: This study compared mobilization and collection variables of a cohort of patients where apheresis was started at the DayCD34peak predicted by the algorithm with a patient group where PBSCs were collected when PB CD34+ cell concentration reached 10 per µL per day (DayCD34threshold). DayCD34peak was calculated according to the equation DayCD34peak = −0.41 × HbD0 + 0.99 × DayCD34threshold + 7.8 (with HbD0 representing the hemoglobin value on Day 0).

RESULTS: The mean number of apheresis procedures per patient based on the DayCD34threshold was 1.74, but decreased to 1.35 when applying the new method (DayCD34peak). For lymphomas, the mean number of apheresis procedures decreased from 1.98 to 1.47 (p = 0.03), while in patients with multiple myeloma it did not change significantly (1.23 and 1.26, respectively). Age and primary disease influenced the number of apheresis procedures needed to achieve the collection target.

CONCLUSION: The application of our algorithm can lower the number of apheresis procedures by improving the timing, especially in patients suffering from malignant lymphomas with a poor marrow potential after several chemotherapy lines.
Post‐Globalization
Authors: GARDELS NATHAN
Published: April 2008

Globalization has so thoroughly transformed the world that we may now be entering a new phase: post‐globalization. This phase is characterized less by a flattening of old differences than the appearance of new ones.
Peeling Away the Western Veneer
Authors: MAHBUBANI KISHORE
Published: April 2008

Globalization has indeed flattened the earth, paving the way for new beginnings and the resurgence of old cultures alike by levelling the playing field for all comers. While this new era of post‐globalization certainly heralds de‐Westernization by century's end, is it more likely to mean a revival of the old ways of the East or the new hybrid ways of the first global civilization?

Some of Asia's most provocative voices, as well as the world's most renowned cellist and cross‐pollinating musician, offer their views.
Paths of Globalization: From the Berbers to Bach
Authors: MA YO‐YO
Published: April 2008

Globalization has indeed flattened the earth, paving the way for new beginnings and the resurgence of old cultures alike by levelling the playing field for all comers. While this new era of post‐globalization certainly heralds de‐Westernization by century's end, is it more likely to mean a revival of the old ways of the East or the new hybrid ways of the first global civilization?

Some of Asia's most provocative voices, as well as the world's most renowned cellist and cross‐pollinating musician, offer their views.
China Must Convince the World Its Rise Is Peaceful
Authors: YEW LEE KUAN
Published: April 2008

Globalization has indeed flattened the earth, paving the way for new beginnings and the resurgence of old cultures alike by levelling the playing field for all comers. While this new era of post‐globalization certainly heralds de‐Westernization by century's end, is it more likely to mean a revival of the old ways of the East or the new hybrid ways of the first global civilization?

Some of Asia's most provocative voices, as well as the world's most renowned cellist and cross‐pollinating musician, offer their views.
This Is Not America's Final Crisis
Authors: ATTALI JACQUES
Published: April 2008

Globalization has indeed flattened the earth, paving the way for new beginnings and the resurgence of old cultures alike by levelling the playing field for all comers. While this new era of post‐globalization certainly heralds de‐Westernization by century's end, is it more likely to mean a revival of the old ways of the East or the new hybrid ways of the first global civilization?

Some of Asia's most provocative voices, as well as the world's most renowned cellist and cross‐pollinating musician, offer their views.
Secularism Is a Women's Affair
Authors: GÖLE NILUFER
Published: April 2008

The drama between the secularist legacy of Ataturk and the popular surge of Islamist‐rooted politics continues in Turkey, centered on the debate over the headscarf. Is it a sign of religious reaction, or a sign of non‐Western modernization that will ensure higher education for Muslim women? We represent here all sides of the debate.

Elsewhere in the Muslim world are the reformers and critics listening to each other, or impeding progress with a blame game? Europe's most controversial figures in this debate—Ayaan Hirsi Ali and Tariq Ramadan—engage here.
Beneath the Headscarf: A Modern Individual
Authors: USLU ZEYNEP KARAHAN
Published: April 2008

The drama between the secularist legacy of Ataturk and the popular surge of Islamist‐rooted politics continues in Turkey, centered on the debate over the headscarf. Is it a sign of religious reaction, or a sign of non‐Western modernization that will ensure higher education for Muslim women? We represent here all sides of the debate.

Elsewhere in the Muslim world are the reformers and critics listening to each other, or impeding progress with a blame game? Europe's most controversial figures in this debate—Ayaan Hirsi Ali and Tariq Ramadan—engage here.
Here We Are: A Response to Ayaan Hirsi Ali
Authors: RAMADAN TARIQ
Published: April 2008

The drama between the secularist legacy of Ataturk and the popular surge of Islamist‐rooted politics continues in Turkey, centered on the debate over the headscarf. Is it a sign of religious reaction, or a sign of non‐Western modernization that will ensure higher education for Muslim women? We represent here all sides of the debate.

Elsewhere in the Muslim world are the reformers and critics listening to each other, or impeding progress with a blame game? Europe's most controversial figures in this debate—Ayaan Hirsi Ali and Tariq Ramadan—engage here.
Beyond the Blame Game
Authors: ANEES MUNAWAR AHMAD
Published: April 2008

The drama between the secularist legacy of Ataturk and the popular surge of Islamist‐rooted politics continues in Turkey, centered on the debate over the headscarf. Is it a sign of religious reaction, or a sign of non‐Western modernization that will ensure higher education for Muslim women? We represent here all sides of the debate.

Elsewhere in the Muslim world are the reformers and critics listening to each other, or impeding progress with a blame game? Europe's most controversial figures in this debate—Ayaan Hirsi Ali and Tariq Ramadan—engage here.
Comprehensive Linkage of Defect and Phase Equilibria Through Ferroelectric Transition Behavior in BaTiO3‐Based Dielectrics: Part 2. Defect Modeling Under Low Oxygen Partial Pressure Conditions
Authors: Lee Soonil , Randall Clive A. , Liu Zi‐Kui
Published: April 2008

Defect and phase equilibria have been investigated through the ferroelectric phase transition behavior of pure and equilibrated nonstoichiometric BaTiO3powders. The paraelectric–ferroelectric phase transition temperature (TC–T) was found to vary systematically with materials fabricated with different Ba/Ti ratio (g*) and under various oxygen partial pressure () conditions.1The solubility regime, as determined through theTC–Tvariation, decreased with decreasing.2Determining the solubility limits and equilibrating the defect reactions at the solubility limits provide a direct approach to calculate the defect formation energies and provide data to test a new defect model for concurrent defect reactions of partial Schottky and reduction defects. A refined approach introduces a balanced equilibrium between the oxygen vacancy concentrations controlled by the partial Schottky and reduction reactions. In the limiting ambient cases the approach gives the expected results, and also fully explains the solubility trends under low's. Universally, the theory supports all the experimental data over different temperatures and's.
Strain‐Induced Relaxor Behavior in PbSc0.50Nb0.25Ta0.25O3 Thin Films: A Comparison with Nanoceramics
Authors: Correa Margarita , Kumar Ashok , Katiyar Ram S.
Published: April 2008

Comparative studies of the microstructure, micro‐Raman spectroscopy, and dielectric properties of PbSc0.50Nb0.25Ta0.25O3 (PSNT) thin films and nanoceramics were carried out over a wide range of temperature (100–520 K) and frequency (100 Hz to 1 MHz). The microstructure of PSNT films revealed an in‐plane compressive strain, whereas PSNT nanoceramics showed an average grain size of 10–15 nm although these nanoordered regions are not capable of producing relaxor behavior. We have observed a shift of 65 K in the dielectric maxima temperature in PSNT films toward the lower temperature side compared with bulk, which confirms the in‐plane compressive strain in the films. We have proposed a dielectric model to calculate the shift in dielectric maxima temperature. Using our experimental data of PSNT thin films, the theoretical model predicted a shift of 62 K in the dielectric maxima temperature, which matched well with our experimental observation. The modified Curie–Wiess law showed a broad relaxation (γ∼2) and a higher disorder level (δ=90 K) for PSNT thin films compared with PSNT nanoceramics having γ∼1.60 and δ=15 K. Well‐behaved hysteresis loops were observed in a broad temperature range for PSNT thin films and slim hysteresis for nanoceramics, indicating a relaxor ferroelectric and diffused ferroelectric phase transition (DFPT) nature, respectively. The temperature‐dependent micro‐Raman spectroscopy revealed that the ferroelectric state in PSNT nanoceramics was accompanied by the appearance of a new peak as a shoulder at ∼80 cm−1 to the lowest F2g mode ∼57 cm−1. Its half‐widths and intensity reduced to zero near the phase transition temperature, whereas the A1g mode showed a doublet namely at (805 and 830 cm−1) below DFPT and an intermediate singlet frequency at 820 cm−1 above DFPT. The micro‐Raman spectra for the thin film matched quite well with the nanoceramics, except that the missing second F2g mode at ∼360 cm−1 was interpreted due to a shorter coherence length in the dipole arrangement in thin films. The in‐plane compressive strain, dipole arrangement, and the size of the nanoordered regions vary the dielectric response of the PSNT films compared with the nanoceramics.
Preparation of Inorganic Compounds at Near Room Temperature by the Direct Conversion of Borate Glass in Solutions of the Corresponding Anions
Authors: Huang Wenhai , Rahaman Mohamed N. , Day Delbert E. , Liu Xin
Published: April 2008

The preparation of alkaline‐earth chromate, selenite, and stannate compounds at near room temperature by the direct conversion of borate glass in aqueous solutions of the corresponding anions was investigated. Borate glass particles (150–300 μm) with the composition 20Na2O·20CaO·60B2O3 or 20Na2O·20BaO·60B2O3 (mol%) were prepared by conventional methods and immersed in dilute solutions of K2CrO4, K2SeO3, or K2SnO3 at 37°C. The conversion of the glasses was monitored using weight loss and pH measurements, while X‐ray diffraction (XRD), X‐ray fluorescence, and scanning electron microscopy were used to characterize the structure and composition of the products. After a reaction for 140–320 h, porous crystalline products identified by XRD as CaSeO3.H2O, CaSnO3.3H2O, BaCrO4, and BaSeO3 were obtained. The conversion of fibers (0.5–1.0 mm in diameter) of the Na2O–BaO–B2O3 glass in K2CrO4 solution was pseudomorphic. The kinetics and mechanisms of the conversion process, as well as the structure of the products, are discussed.
Egg resorption behaviour by the solitary egg parasitoid Anaphes nitens under natural conditions
Authors: Carbone Serena Santolamazza , Nieto Montserrat Pestaña , Rivera Adolfo Cordero
Published: April 2008

We investigated under outdoor conditions and inside a climate chamber: (i) whether Anaphes nitens Girault (Hymenoptera: Mymaridae), an egg parasitoid of the Eucalyptus snout beetle, Gonipterus scutellatus Gyllenhal (Coleoptera: Curculionidae), experienced egg resorption, and (ii) how various treatments (location, food, and/or host supply) and body size influenced egg load, egg resorption, fecundity, and longevity. One‐day‐old females were mated and randomly assigned to five groups: (A) honey + hosts, (B) water + hosts, (C) only honey, (D) only water, and (E) control females killed at emergence. We compared the egg load of the newly emerged females, which represent the control group (egg load = ovarian eggs present at emergence), with the lifetime egg load (i.e., ovarian eggs + emerged offspring + not emerged offspring) of the females with various host and diet treatments, by dissection of the ovaries to find evidence of egg resorption. All groups reared outdoors had fewer eggs than the control, while indoors there was no significant difference. Outdoors, starved but host‐provided wasps (B) experienced the highest reduction of the lifetime egg load (51%). Groups without access to food (B + D) resorbed more eggs than groups provided with honey (A + C). Females with honey and hosts (A) had the highest lifetime fecundity, but those with water and hosts (B) showed a higher daily realized fecundity. Host‐deprived females with access to food (C) attained the longest lifespan. Our results suggest that under stress conditions, such as low temperature and food shortage, A. nitens females practice egg resorption, probably to save energy.
A comparative study on the efficacy of a pest‐specific and prey‐marking enzyme‐linked immunosorbent assay for detection of predation
Authors: Mansfield Sarah , Hagler James R. , Whitehouse Mary E. A.
Published: April 2008

The efficacy of two different antigen–antibody combinations to detect predation on eggs of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) was compared. The first method was an indirect enzyme‐linked immunosorbent assay (ELISA) using monoclonal antibody‐based gut content analysis that detects H. armigera egg protein. The second method was a sandwich ELISA that detects an exotic protein [rabbit immunoglobulin G (IgG)] applied as an external marker to H. armigera eggs. The target predators were the predatory beetles Dicranolaius bellulus (Guerin‐Meneville) (Coleoptera: Melyridae) and Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae). Beetles were fed with H. armigera eggs that had been marked with rabbit IgG and then held at various intervals after prey consumption. Each individual beetle was then assayed by both ELISA techniques to identify the prey remains in their guts. The two ELISA methods were further tested on field‐collected predators. Specifically, protein‐marked egg masses were strategically placed in a cotton field. Then, predators from surrounding cotton plants were collected at various time intervals after the marked eggs were exposed and assayed by both ELISAs to detect the frequency of predation on the marked eggs. The rabbit IgG‐specific sandwich ELISA had a higher detection rate than the H. armigera‐specific indirect ELISA under controlled and field conditions for both predator species. Moreover, a greater proportion of field‐collected D. bellulus tested positive for predation than H. variegata. The advantages and disadvantages of using prey‐marking ELISAs instead of pest‐specific ELISA assays are discussed.
Immunosuppression induced by immature dendritic cells is mediated by TGF‐β/IL‐10 double‐positive CD4+ regulatory T cells
Authors: Cools N. , Van Tendeloo V.F.I. , Smits E.L.J.M. , Lenjou M. , Nijs G. , Van Bockstaele D.R. , Berneman Z.N. , Ponsaerts P.
Published: April 2008

Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady‐state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)‐β and interleukin (IL)‐10 double‐positive CD4+ T cells within 1 week of autologous DC/T cell co‐cultures. In iDC/T cell cultures, where antigen‐specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF‐β and IL‐10 secreted by CD4+CD25−FOXP3− T cells. In addition, the suppressive capacity of CD4+ T cells conditioned by iDC was transferable to already primed antigen‐specific CD8+ T cell cultures. In contrast, addition of CD4+ T cells conditioned by mDC to primed antigen‐specific CD8+ T cells resulted in enhanced CD8+ T cell responses, notwithstanding the presence of TGF‐β+/IL‐10+ T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine‐secreting regulatory T cells. We show that iDC‐conditioned CD4+ T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4+ T cells. Furthermore, TGF‐β+/IL‐10+ T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.
ARG3.1/ARC expression in hippocampal dentate gyrus astrocytes: ultrastructural evidence and co‐localization with glial fibrillary acidic protein
Authors: Rodríguez J. J. , Davies H. A. , Errington M. L. , Verkhratsky A. , Bliss T. V. P. , Stewart M. G.
Published: April 2008

Synaptic efficacy following long‐term potentiation (LTP) and memory consolidation is associated with changes in the expression of immediate early genes (IEGs). These changes are often accompanied by increased expression of glial fibrillary acidic protein (GFAP). While the protein products of the majority of IEGs are mainly restricted to the cell body, Arg3.1/Arc product is rapidly delivered to dendrites, where it accumulates close to synaptic sites. Arg3.1/Arc protein was originally considered neurone specific; however, we have recently found Arg3.1/Arc immunoreactivity (Arg3.1/Arc‐IR) within glial cells and demonstrated its increased expression after LTP in the hippocampal dentate gyrus (DG). Here, we have further investigated this novel finding, using electron microscopic immunocytochemistry to determine the localization and sub‐cellular distribution of Arg3.1/Arc protein in GFAP positive glia (GFAP‐IR) in the DG. Arg3.1/Arc labelling was seen prominently in GFAP‐IR glial cell bodies and in large‐ and medium‐sized glial filamentous processes. GFAP‐labelled medium–small peri‐synaptic glial profiles also displayed Arg3.1/Arc‐IR; however, the very thin and distal glial filaments only displayed Arc‐IR. Arc‐IR was distributed throughout the cytoplasm, often associated with GFAP filaments, and along the plasma membrane of glial processes. Peri‐synaptic glial Arg3.1/Arc‐IR processes were apposed to pre‐ and/or post‐synaptic profiles at asymmetric axospinous synapses. These data, taken with our earlier study which provided evidence for an increase in astrocytic Arg3.1/Arc‐IR after the induction of LTP, suggest a role for glial Arg3.1/Arc in structural and synaptic plasticity which may be critical for the maintenance of cognitive functions.
Consequences of altered eicosanoid patterns for nociceptive processing in mPGES‐1‐deficient mice
Authors: Brenneis Christian , Coste Ovidiu , Schmidt Ronald , Angioni Carlo , Popp Laura , Nusing Rolf M. , Becker Wiebke , Scholich Klaus , Geisslinger Gerd
Published: April 2008

Cyclooxygenase‐2 (COX‐2)‐dependent prostaglandin (PG) E2synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2synthase‐1 (mPGES‐1) isomerizes COX‐2‐derived PGH2to PGE2. Here, we evaluated the effect of mPGES‐1‐deficiency on the noci‐ceptive behavior in various models of nociception that depend on PGE2synthesis. Surprisingly, in the COX‐2‐dependent zymosan‐evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES‐1‐deficient mice despite a marked decrease of the spinal PGE2synthesis. Similarly, the nociceptive behavior was unaltered in mPGES‐1‐deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES‐1‐deficient mice showed a redirection of the PGE2synthesis to PGD2, PGF2αand 6‐keto‐PGF1α(stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci‐ception they may compensate the loss of PGE2synthesis in mPGES‐1‐deficient mice.
Pro‐inflammatory effects of hydrogen sulphide on substance P in caerulein‐induced acute pancreatitis
Authors: Bhatia Madhav , Sidhapuriwala Jenab N. , Wei Ng Siaw , Tamizhselvi Ramasamy , Moochhala Shabbir M.
Published: April 2008

Hydrogen sulphide (H2S), a novel gasotransmitter, has been recognized to play an important role in inflammation. Cystathionine‐γ‐lyase (CSE) is a major H2S synthesizing enzyme in the cardiovascular system and DL‐propargylglycine (PAG) is an irreversible inhibitor of CSE. Substance P (SP), a product of preprotachykinin‐A (PPT‐A) gene, is a well‐known pro‐inflammatory mediator which acts principally through the neurokinin‐1 receptor (NK‐1R). We have shown an association between H2S and SP in pulmonary inflammation as well as a pro‐inflammatory role of H2S and SP in acute pancreatitis. The present study was aimed to investigate the interplay between pro‐inflammatory effects of H2S and SP in a murine model of caerulein‐induced acute pancreatitis. Acute pancreatitis was induced in mice by 10 hourly intraperitoneal injections of caerulein (50 (g/kg). PAG (100 mg/kg, i.p.) was administered either 1 hr before (prophylactic) or 1 hr after (therapeutic) the first caerulein injection. PAG, given prophylactically as well as therapeutically, significantly reduced plasma H2S levels and pancreatic H2S synthesizing activities as well as SP concentrations in plasma, pancreas and lung compared with caerulein‐induced acute pancreatitis. Furthermore, prophylactic as well as therapeutic administration of PAG significantly reduced PPT‐A mRNA expression and NK‐1R mRNA expression in both pancreas and lung when compared with caerulein‐induced acute pancreatitis. These results suggest that the pro‐inflammatory effects of H2S may be mediated by SP‐NK‐1R pathway in acute pancreatitis.
Opposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytes
Authors: Mazzola Alessia , Amoruso Emanuela , Beltrami Elena , Lecca Davide , Ferrario Silvia , Cosentino Simona , Tremoli Elena , Ceruti Stefania , Abbracchio Maria P.
Published: April 2008

We previously showed that the human heart expresses all known P2X and P2Y receptors activated by extra‐cellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine‐ and uracil‐preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL‐1 cardiomyocytes. RT‐PCR analysis showed that HL‐1 cardiomyocytes express all known P2X receptors (except for P2X2), as well as the P2Y2,4,6,14subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow‐cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)‐α, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect ‘per se’, but fully counteracted the deleterious effects induced by adenine nucleotides and TNF‐α, even if added to cardiomyocytes after beginning exposure to these cell death‐inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the presence of TNF‐α contributes to cell death, an effect which is counteracted by uracil‐preferring P2 receptors. Cardiomyocytes do not need to be ‘primed’ by uracil nucleotides to become insensitive to adenine nucleotides‐induced death, suggesting the existence of a possible ‘therapeutic’ window for uracil nucleotides‐mediated protection. Thus, release of UTP during cardiac ischaemia and in chronic heart failure may protect against myocardial damage, setting the basis for developing novel cardioprotective agents that specifically target uracil‐preferring P2Y receptors.
Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy
Authors: Docheva Denitsa , Padula Daniela , Popov Cvetan , Mutschler Wolf , Clausen‐Schaumann Hauke , Schieker Matthias
Published: April 2008

Within the bone lie several different cell types, including osteoblasts (OBs) and mesenchymal stem cells (MSCs). The MSCs are ideal targets for regenerative medicine of bone due to their differentiation potential towards OBs. Human MSCs exhibit two distinct morphologies: rapidly self‐renewing cells (RS) and flat cells (FC) with very low proliferation rates. Another cell type found in pathological bone conditions is osteosarcoma. In this study, we compared the topographic and morphometric features of RS and FC cells, human OBs and MG63 osteosarcoma cells by atomic force microscopy (AFM). The results demonstrated clear differences: FC and hOB cells showed similar ruffled topography, whereas RS and MG63 cells exhibited smoother surfaces. Furthermore, we investigated how selected substrates influence cell morphometry. We found that RS and MG63 cells were flatter on fibrous substrates such as polystyrene and collagen I, but much more rounded on glass, the smoothest surface. In contrast, cells with large area, namely FC and hOB cells, did not exhibit pronounced changes in flatness with regards to the different substrates. They were, however, remarkably flatter in comparison to RS and MG63 cells. We could explain the differences in flatness by the extent of adhesion. Indeed, FC and hOB cells showed much higher content of focal adhesions. Finally, we used the AFM to determine the cellular Young's modulus. RS, FC and hOB cells showed comparable stiffness on the three different substrates, while MG63 cells demonstrated the unique feature of increased elasticity on collagen I. In summary, our results show, for the first time, a direct comparison between the morphometric and biophysical features of different human cell types derived from normal and pathological bone. Our study manifests the opinion that along with RNA, proteomic and functional research, morphological and biomechanical characterization of cells also reveals novel cell features and interrelationships.
The unfolded protein response in hereditary haemochromatosis
Authors: De Almeida S.F. , De Sousa M.
Published: April 2008

To cope with the accumulation of unfolded or misfolded proteins the endoplasmic reticulum (ER) has evolved specific signalling pathways collectively called the unfolded protein response (UPR). Elucidation of the mechanisms governing ER stress signallinghas linked this response to the regulation of diverse physiologic processes as well as to the progression of a number of diseases. Interest in hereditary haemochromatosis (HH) has focused on the study of proteins implicated in iron homeostasis and on the identification of new alleles related with the disease. HFE has been amongst the preferred targets of interest, since the discovery that its C282Y mutation was associated with HH. However, the discrepancies between the disease penetrance and the frequency of this mutation have raised the possibility that its contribution to disease progression might go beyond the mere involvement in regulation of cellular iron uptake. Recent findings revealed that activation of the UPR is a feature of HH and that this stress response may be involved in the genesis of immunological anomalies associated with the disease. This review addresses the connection of the UPR with HH, including its role in MHC‐I antigen presentation pathway and possible implications for new clinical approaches to HH.
The functions and possible significance of Kremen as the gatekeeper of Wnt signalling in development and pathology
Authors: Nakamura T , Nakamura T , Matsumoto K
Published: April 2008

Introduction

Identification and structure of Krm

Krm as a negative regulator in Wnt signalling

Expression of Krm

Krm in development

Wnt signalling in stem cell regulation and diseases

Wnt signalling, Krm and cancer

Perspectives

Kremen (Krm) was originally discovered as a novel transmembrane protein containing the kringle domain. Both Krm1 (the first identified Krm) and its relative Krm2 were later identified to be the high‐affinity receptors for Dickkopf (Dkk), the inhibitor of Wnt/β‐catenin signalling. The formation of a ternary complex composed of Krm, Dkk, and Lrp5/6 (the coreceptor of Wnt) inhibits Wnt/β‐catenin signalling. In Xenopus gastrula embryos, Wnt/β‐catenin signalling regulates anterior‐posterior patterning, with low‐signalling in anterior regions. Inhibition of Krm1/2 induces embryonic head defects. Together with anterior localization of Krms and Dkks, the inhibition of Wnt signalling by Dkk‐Krm action seems to allow anterior embryonic development. During mammalian development, krm1 mRNA expression is low in the early stages, but gradually and continuously increases with developmental progression and differentiation. In contrast with the wide, strong expression of krm1 mRNA in mature tissues, expression of krm1 is diminished in a variety of human tumor cells. Since stem cells and undifferentiated cells rely on Wnt/β‐catenin signalling for maintenance in a low differentiation state, the physiological shutdown of Wnt/β‐catenin signalling by Dkk‐Krm is likely to set cells on a divergent path toward differentiation. In tumour cells, a deficit of Krm may increase the susceptibility to tumourigenic transformation. Both positive and negative regulation of Wnt/β‐catenin signalling definitively contributes to diverse developmental and physiological processes, including cell‐fate determination, tissue patterning and stem cell regulation. Krm is quite significant in these processes as the gatekeeper of the Wnt/β‐catenin signalling pathway.
Histology far away from Flatland: 3D roller‐coasting into grade‐dependent angiogenetic patterns in oligodendrogliomas
Authors: Cassoni P. , Gaetano L. , Senetta R. , Bussolati B. , Molinaro L. , Bussolati G.
Published: April 2008

Angiogenesis plays a key role in tumour progression, and undergoes structural changes associated to tumour biology itself. Although vessel density can be easily evaluated in brain tumours using a traditional immuno‐histochemical approach, other parameters of conceptual/biological interest, such as the complex patterns of vascular growth, cannot be fully understood using a traditional bi‐dimensional evaluation. We use here surgical specimens derived from oligodendrogliomas as a model for a novel elucidative 3D reconstruction of the grade‐dependent vascular arborisation in brain tumours.
Neural stem cells, inflammation and NF‐κB: basic principle of maintenance and repair or origin of brain tumours?
Authors: Widera D. , Kaus A. , Kaltschmidt C. , Kaltschmidt B.
Published: April 2008

Neural Stem Cells

Inflammation, NF‐κB and neural stem cells

Inflammation, NF‐κB and cancer

NSCs and brain cancer

NF‐κB target genes affecting NSCs and tumour formation

Conclusion

Several recent reports suggest that inflammatory signals play a decisive role in the self‐renewal, migration and differentiation of multipotent neural stem cells (NSCs). NSCs are believed to be able to ameliorate the symptoms of several brain pathologies through proliferation, migration into the area of the lesion and either differentiation into the appropriate cell type or secretion of anti‐inflammatory cytokines. Although NSCs have beneficial roles, current evidence indicates that brain tumours, such as astrogliomas or ependymomas are also caused by tumour‐initiating cells with stem‐like properties. However, little is known about the cellular and molecular processes potentially generating tumours from NSCs. Most pro‐inflammatory conditions are considered to activate the transcription factor NF‐κB in various cell types. Strong inductive effects of NF‐κB on proliferation and migration of NSCs have been described. Moreover, NF‐κB is constitutively active in most tumour cells described so far. Chronic inflammation is also known to initiate cancer. Thus, NF‐κB might provide a novel mechanistic link between chronic inflammation, stem cells and cancer. This review discusses the apparently ambivalent role of NF‐κB: physiological maintenance and repair of the brain via NSCs, and a potential role in tumour initiation. Furthermore, it reveals a possible mechanism of brain tumour formation based on inflammation and NF‐κB activity in NSCs.
Molecular mechanism of regulation of the calcium‐binding protein calbindin‐D9k,and its physiological role(s) in mammals: a review of current research
Authors: Choi Kyung‐Chul , Jeung Eui‐Bae
Published: April 2008

Introduction

Phenotype ofCaBP‐9kknockout mouse

Uterine expression and regulation of CaBP‐9k

Placental expression and regulation ofCaBP‐9k

Duodenal and renal expression and regulation of CaBP‐9k

Pituitary expression and regulation of CaBP‐9k

Transcriptional regulation of CaBP‐9k

Conclusions

Calbindin‐D9k(CaBP‐9k) is a cytosolic calcium‐binding protein that is expressed in a variety of tissues, such as uterus, placenta, intestine, kidney, pituitary gland and bone. At present, the precise role(s) of CaBP‐9k remains to be clarified. CaBP‐9k‐null mice are normal, which indicates that other calcium‐transporter genes can compensate for the lack CaBP‐9k. Uterine CaBP‐9k has been shown to be involved in the regulation of myometrial activity by intracellular calcium. In the uterus and placenta,CaBP‐9kexpression is regulated by the sex steroid hormones oestrogen (E2) and progesterone (P4). IntestinalCaBP‐9kis involved in intestinal calcium absorption, and is regulated at the transcriptional and post‐transcriptional levels by 1,25‐dihydroxyvitamin D3, the hormonal form of vitamin D. Thus, evidence to date suggests thatCaBP‐9kmay be regulated in a tissue‐specific manner. In this review, we will summarize current data on the molecular mechanism of regulation ofCaBP‐9kin mammals, including recent research data generated in our laboratories.
Mouse models with human immunity and their application in biomedical research
Authors: Zhang Baojun , Duan Ziyuan , Zhao Yong
Published: April 2008

Introduction

Recipient mouse selection for engrafting xenogeneic human haematopoietic and immune cells

Pre‐conditioning regimens for establishing humanized mice

Transplantation strategies to establish humanized mice

A proposed ideal humanized mouse model

Applications of humanized mouse models in biomedical research

Conclusions and perspectives

Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)null mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Ragnull mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non‐genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well.
Histopathological changes in collagen and matrix metalloproteinase levels in articular condyle of experimental model rats with jaw deformity
Authors: Watanabe A , Yamaguchi M , Utsunomiya T , Yamamoto H , Kasai K
Published: April 2008

Structured Abstract

Authors –  Watanabe A, Yamaguchi M, Utsunomiya T, Yamamoto H, Kasai K

Objective –  To investigate the dynamics of the cartilage matrix in the articular condyle after removal of a side shift plate; Emergence of type I, II, and III collagen in the matrix as well as changes in levels of matrix metalloproteinase (MMP)‐1, ‐8, and ‐13 that degrade collagen were studied histopathologically and immunohistochemically.

Design –  Lateral displacement of the mandible was achieved by attaching a side shift plate to the anterior teeth of the maxilla in male rats at 6 weeks. The wearing period of the side shift plate was 8 weeks. Observations were made at 0, 1, 2, 4 and 8 weeks after removal.

Results –  In histopathological findings, the timing of proliferation of the layer of hypertrophy varied between the bilateral sides. In immunohistochemical findings a significant decline in the expression of type II collagen in the displacement side was observed immediately after removal. Moreover, the expressions of MMPs were elevated in both sides on 0 weeks. At 1 week after removal, a significant elevated in the expression of type II collagen, MMPs was decline in both sides.

Conclusions –  After removal, the levels of MMP‐1, ‐8, and 13 were reduced and the emergence of type II collagen increased. Thus, cellular outgrowth was initiated to trigger intracartilaginous ossification to restore the cartilage matrix.
Exchange transfusion in infants with extreme hyperbilirubinemia: an experience from a developing country
Authors: Salas Ariel A , Mazzi Eduardo
Published: April 2008

Objective: To determine the clinical and epidemiological features of infants with extreme hyperbilirubinemia who require exchange transfusion (ET).

Study design: Term and near‐term infants admitted to a paediatric hospital over a 5‐year period in La Paz, Bolivia, were included in the study if they met the following criteria: age less than 30 days; total serum bilirubin (TSB) levels ≥428 μmol/L (≥25 mg/dL) on admission and if they had undergone an ET.

Results: Fifty‐six infants were identified during the study period. Most of them were exclusively breastfed (98.2%). Median age at admission was 7 days. Weight loss of more than 12% since birth, as well as dehydration, was registered in more than one‐third of cases. Extreme hyperbilirubinemia was considered as secondary to increased enterohepatic circulation (EHC) in most cases (73%). The mean TSB level on admission was 531.8 μmol/L (31.1 mg/dL). Fifteen infants (26.8%) showed signs of acute bilirubin encephalopathy (ABE). Early ABE was reversible after ET in most cases but all infants with advanced ABE developed severe kernicteric sequelae. Nine patients (16.1%) developed adverse events attributable to ET.

Conclusions: Dehydration and weight loss in breastfed infants appeared to be an important factor associated with extreme hyperbilirubinemia and secondary brain damage during the first week of life. This may well be avoided if signs of ABE and its associated conditions are identified appropriately by follow‐up programmes.
A new technique for transumbilical insertion of central venous silicone catheters in newborn infants
Authors: Haumont D , De Beauregard V Gouder , Van Herreweghe I , Delanghe G , Ciardelli R , Haelterman E
Published: April 2008

Aim: A new technique allowing placement of umbilical silicone venous catheters (USVC) is described and compared with percutaneous silicone venous catheters (PSVC).

Methods: Data were retrospectively recorded for 198 infants with USVC and 141 infants with PSVC.

Results: Overall rate of complications was low and comparable in both groups: thrombosis 1.2%, catheter‐related sepsis 3.5% and mechanical obstruction 5%.

Conclusion: A new device allows safe introduction of silicone catheters into the umbilical vein.
Christians and Jews: Competitive Siblings or the Israel of God?
Authors: McDade John
Published: April 2008

Dabru Emet, the important statement by Jewish scholars on the religious significance of Christianity and the Jewish relation to the Church, stimulated an articulate debate among Jews: Jon Levenson fears that the anodyne character of Dabru Emet lacks a conceptually coherent pluralism and commits Jews to positions which alter the fundamental character of Judaism. Does dialogical engagement with another tradition substantially modify the features of a religion? The Christian theologian Paul van Buren outlines three stages in the relationship of the two faiths which seem to lead to radical revision, certainly of Christianity. Van Buren's approach raises the question of the weighting accorded to different ‘moments’ in the dynamic of revelation springing from Israel. If Christianity is ‘reconfigured Judaism’, and the relation to Judaism is at the heart of Christian identity, then the two traditions exercise a conjoined, single mission on behalf of the truth of God. Israel according to the flesh and the community of reconfigured Israel are two communities, focused upon different but inseparable moments in ‘the design of the Lord of the covenant’, which might be designated as ‘the Israel of God’.
Theological Issues in Christian-Muslim Dialogue
Authors: Hewer Chris
Published: April 2008

An initial analysis of the theological aspects of Christian-Muslim relations. After setting the historical scene, the following theological issues are briefly explored: consequences of two faiths worshipping God, prophethood of Muhammed, status of the Qur'an, Jesus as “Son of God”, a Qur'anic Christology, “People of the Book” vs. “People of the Incarnate Revelation”, the divine/human relationship in heaven, salvation and original sin, free-will and predeterminism, unicity of God vs. Trinity, Unitarians as “true Christians”, death and resurrection vs. “undead ascension”, and has the magisterium of the Church distorted the true message of Jesus? Three dimensions of the issues are covered: Content: what are the theological issues? Method: how do we handle the issues? Consequences: what difference might that make for Christian theological reflection? The challenge is to develop a methodology that moves beyond polemic or apologetics, that recognises the limitations of understanding and that returns theological discourse to the realm of faith and accountability before God.