bluuebunny/crossref_metadata_2025 huggingface dataset:
Das EnergieWertHaus als Beitrag zum nachhaltigen Mauerwerksbau
Authors: Heße Markus
Published: April 2008

Nicht nur die Nachhaltigkeit beim Bauen steht beim EnergieWertHaus von Xella im Vordergrund, sondern auch der nachhaltige Umgang mit den Ressourcen zum Betrieb dieses Hauses. Die einzelnen Komponenten des Konzeptes greifen eng verzahnt ineinander und schaffen damit den entscheidenden Beitrag dafür, dass ein EnergieWertHaus auf Zukunft gebaut wird. Der Beitrag zu dem Thema erläutert sowohl die technischen Bestandteile als auch das Marketingnetzwerk für dieses bundesweit bisher einmalige Konzept für den modernen Mauerwerksbau. Vor dem Hintergrund des fortschreitenden Klimawandels soll hiermit ein Beitrag zum ressourcenschonenden Bauen und Betrieb von Immobilien aufgezeigt werden, der im gesamten Lebenszyklus des Gebäudes stets das ökologische Gleichgewicht im Fokus hat.
B cell activation regulates exosomal HLA production
Authors: Arita Shuji , Baba Eishi , Shibata Yoshihiro , Niiro Hiroaki , Shimoda Shinji , Isobe Taichi , Kusaba Hitoshi , Nakano Shuji , Harada Mine
Published: April 2008

Exosomes are nanovesicles produced constitutively and inducibly by several types of cells. They are generated as intraluminal vesicles of multivesicular bodies and express MHC and several endosomal/lysosomal proteins. In spite of their potential role in cellular immunity, the regulatory mechanisms of exosome production are largely unknown. In this study, we have established a novel ELISA system to quantify exosomal HLA using a combination of anti‐HLA class I and anti‐HLA‐DR mAb. We found that exosomal HLA production of B cells was enhanced by contact with CD4+ T cells. Neutralizing anti‐CD154 (CD40L) mAb inhibited this effect, and a soluble CD40L significantly increased production of exosomal HLA in B cells. In addition, B cell stimulation via BCR and TLR9 enhanced their production while IL‐4 stimulation alone failed to do so. Strikingly, an inhibitor of the classical NF‐κB pathway drastically inhibited exosomal HLA production in stimulated B cells, indicating that the classical NF‐κB pathway is critical for exosomal HLA production in B cells. Together, these findings suggest a pivotal role of B cell activation in exosomal HLA production in vivo.

See accompanying article: http://dx.doi.org/10.1002/eji200838374
Airway epithelial cells modify immune responses by inducing an anti‐inflammatory microenvironment
Authors: Mayer Anja K. , Bartz Holger , Fey Fabian , Schmidt Lotte M. , Dalpke Alexander H.
Published: April 2008

The upper airways are prone to contact with pathogenic as well as non‐pathogenic microbes, therefore immune recognition principles have to be tightly controlled. Here we show that human BEAS‐2B bronchial epithelial cells inhibited secretion of the pro‐inflammatory cytokines TNF‐α and IL‐12 by monocytes, macrophages and dendritic cells. This inhibitory effect could be transferred by supernatant of resting BEAS‐2B cells and was also observed when primary murine tracheal epithelial cells were prepared. In contrast to inhibition of pro‐inflammatory cytokine secretion epithelial cell‐conditioned dendritic cells showed increased expression of IL‐10 and arginase‐1, thus displaying properties of alternative activation. Accordingly, Toll‐like receptor‐mediated up‐regulation of CD40, CD86 and PD‐L2 (CD273) on murine dendritic cells was reduced in the presence of bronchial epithelial cell supernatant. However, expression of negative regulatory PD‐L1 (CD274) was increased and dendritic cell induced proliferation of T lymphocytes was diminished. Epithelial cells also showed a direct inhibitory effect on T lymphocyte proliferation and this was due to the constitutive secretion of TGF‐β by bronchial epithelial cells. Moreover, epithelial cell‐conditioned T lymphocytes showed increased differentiation towards IL‐10‐producing Tr1 cells. The results indicate that bronchial epithelial cells induce a non‐inflammatory microenvironment that regulates local immune homeostasis.
Activation of myelin reactive T cells in multiple sclerosis: A possible role for T cell degeneracy?
Authors: Stinissen Piet , Hellings Niels
Published: April 2008

While it is widely accepted that myelin reactive T cells are key players in the immunopathogenesis of multiple sclerosis (MS), the initial triggers that turn on these self‐reactive T‐cells remain to be determined. One mechanism, which is already text book knowledge for a decade, is molecular mimicry by which viral or microbial antigens are able to cross‐activate T cells specific for myelin epitopes, the major target in MS pathology. Although proof of concept for this principle was given in animal model studies, evidence for such a mechanism in MS is limited. In this issue, Zhang et al. demonstrate an increased frequency of T cells that cross‐react with a wide variety of antigens, a phenomenon termed as T cell degeneracy. While the role of these degenerate T cells in MS remains to be determined the authors now provide new elegant tools to study this T cell population, thus providing a starting point to better understand their function in MS.

See accompanying article http://dx.doi.org/10.1002/eji200737519
Cover Picture: Nanoparticles target distinct dendritic cell populations according to their size – Eur. J. Immunol. 5/2008
Authors: Manolova Vania , Flace Anna , Bauer Monika , Schwarz Katrin , Saudan Philippe , Bachmann Martin F.
Published: April 2008

The cover shows a colour series of mouse footpads injected with small fluorescent nanoparticles. The image depicts the afferent lymphatic vessels connecting the injection site with the draining popliteal lymph node and the more distal sciatic lymph node. Lymphatic vessels (in green in the left row) run together with the veins (darker curves) and carry free draining antigen to the lymph nodes. This image was provided by the authors of Manolova (pp.

1404–1413)

, in which it is demonstrated that particle size critically influences the mode of antigen transport to the draining lymph nodes; DC are strictly required for transport of large (500–2000 nm) particles, whereas smaller particles (20–200 nm), such as virus‐like particles (30 nm), drain freely.
CE‐MSn of complex pectin‐derived oligomers
Authors: Coenen Gerd‐Jan , Kabel Mirjam A. , Schols Henk A. , Voragen Alphons G. J.
Published: April 2008

As pectin molecules are too large and heterogeneous to analyze as a whole, the polymer is usually degraded to smaller oligomers, which are often analyzed by high‐performance anion exchange chromatography (HPAEC). However, the high salt concentration necessary to elute pectin oligomers by HPAEC is incompatible with online mass detection. To overcome such a disadvantage, a CE‐IT‐MS system was set up to further elucidate the fine structure of charged oligosaccharides. An effective separation of differently substituted galacturonic acid containing oligomers was obtained by low‐pH CE‐LIF analysis. By adapting the buffer and capillary online MS detection was enabled. Moreover, with MS/MS it was possible to localize sugar residues' substitutions. With this combined CE‐MS approach LIF electropherograms of xylogalacturonan and rhamnogalacturonan I digests could be annotated. The method was further exemplified by a complex oligomer mixture of acid hydrolyzed apple pectin, which was separated and characterized by CE‐MSn. Oligomers present in low amounts could be localized by their corresponding m/z, as was demonstrated by selected mass range representation.
Characterization of Atropa belladonna L. compounds by capillary electrophoresis‐electrospray ionization‐time of flight‐mass spectrometry and capillary electrophoresis‐electrospray ionization‐ion trap‐mass spectrometry
Authors: Arráez‐Román David , Zurek Gabriela , Bäßmann Carsten , Segura‐Carretero Antonio , Fernández‐Gutiérrez Alberto
Published: April 2008

This short communication describes the characterization of seven tropane alkaloid compounds in Atropa belladonna L. Thus a rapid and easy CE‐electrospray interface (ESI)‐TOF‐MS procedure is developed to analyze these compounds in a pharmaceutical preparations of A. belladonna L. leaf extract. Optimum electrophoretic separation is obtained using an alkaline solution of 60 mM ammonium acetate at pH 8.5 containing 5% isopropanol. Under the optimum CE‐ESI‐TOF‐MS conditions several important compounds such as tropine, belladonnine, norhyoscyamine, apoatropine, hyoscyamine, 6β‐hydroxyhyoscyamine, and scopolamine have been simultaneously identified from A. belladonna L. CE‐ESI‐IT‐MS has been used to discriminate the putative presence of littorine. The sensitivity, together with mass accuracy and true isotopic pattern of the TOF‐MS, allowed the identification of a broad series of tropane alkaloid compounds present in pharmaceutical preparations of A. belladonna L. leaf extract.
Characterization of intact lipopolysaccharides from the Haemophilus influenzae strain RM 118 using electrophoresis‐assisted open‐tubular liquid chromatography‐mass spectrometry
Authors: Dzieciatkowska Monika , Schweda Elke K. H. , Moxon E. Richard , Richards James C. , Li Jianjun
Published: April 2008

We have applied an electrophoresis‐assisted open‐tubular LC‐MS method for analyzing intact lipopolysaccharides (LPSs) from Haemophilus influenzae strain RM118 (Rd). We were able to obtain structural information on both core oligosaccharides (OSs) and the lipid A moiety including the sialylation, glycylation, and the distribution of fatty acid residues on the disaccharide backbone of lipid A. The fragmentation patterns of sodiated and protonated LPS molecules were investigated for determining the location of sialic acid. It was found that the tandem mass spectra of sodiated ions provided unambiguous evidence of both sialylated lactose and sialylated lacto‐N‐neotetraose. In contrast, the fragment ions of protonated ions only offered the evidence for the existence of sialylated lacto‐N‐neotetraose. The lipid A of Gram‐negative bacteria, as the principal endotoxic component of LPS, plays a major role in the pathogenesis of bacterial infections. We have previously characterized lipid A species after mild acid hydrolysis of LPS during which lipid A precipitates. In this study, intact LPS was directly introduced to a tandem mass spectrometer. In‐source dissociation strategy was employed, followed by multiple‐stage MS/MS on the ions originating from the lipid part to obtain structural information. This is the first time that the structure of lipid A of H. influenzae was characterized by MS/MS on intact LPS molecules without any prior chemical modifications. In the same way information on the OS can be obtained by MS/MS by focusing on ions originating from core OS.
Determination of sialic acids released from glycoproteins using capillary zone electrophoresis/electrospray ionization mass spectrometry
Authors: Ortner Karin , Buchberger Wolfgang
Published: April 2008

A simple method for the determination of the two most abundant sialic acids released from glycoproteins based on CZE‐MS is presented. Several parameters like BGE with various organic modifiers and sheath liquids were studied with respect to their suitability for the fast and easy analysis of the selected compounds by CZE‐MS. Finally, a BGE containing 10 mM ammonium acetate allowed the quantification of N‐acetylneuraminic acid (Neu5Ac) and N‐glycolylneuraminic acid (Neu5Gc) in glycoproteins as well as human plasma samples. LOD and LOQ were 2 µg/mL and 6 µg/mL, respectively.
Capillary isoelectric focusing hyphenated to single‐ and multistage matrix‐assisted laser desorption/ionization‐mass spectrometry using automated sheath‐flow‐assisted sample deposition
Authors: Lechner Michael , Seifner Alexandra , Rizzi Andreas M.
Published: April 2008

In this paper CIEF combined with MALDI‐MS is described using a sheath‐liquid‐assisted automatic sample deposition from the separation capillary onto a MALDI target. Sample/matrix preparation techniques on the target resembling the dried droplet and the thin layer methods were evaluated in the context of the automatic spotting. Volatile buffers were used as IEF catholyte solutions. Test samples consisting of tryptic peptides, glycopeptides, and phosphopeptides of well‐known proteins showed that CIEF‐MALDI‐MS can be used as effective preseparation method prior to MS, allowing to obtain the amino acid sequence coverage of proteins similar to that achieved with CZE‐MALDI‐MS and CZE‐ESI‐MS. Particularly, completeness and reliability of glycopeptide analysis is much enhanced by the preseparation. The effect is less pronounced but still significantly found with phosphopeptides present in the test protein. Finally, a test sample of five standard proteins demonstrates the suitability of this technique also for the treatment of intact proteins. This technique has potential to emerge as a faster method analogous and complementary to 2‐DE and to IPG‐IEF‐MALDI‐MS demonstrated before by the group of Loo [1].
Nonaqueous capillary electrophoresis‐electrospray ionization‐ion trap‐mass spectrometry analysis of pyrrolo‐ and pyrido[1,2‐a]azepine alkaloids in Stemona
Authors: Sturm Sonja , Schinnerl Johann , Greger Harald , Stuppner Hermann
Published: April 2008

Stemona alkaloids represent an outstanding class of natural compounds due to their pharmacological profile and their complex and unusual molecular structures. The aim of this study was the development of the first CE method for the separation, identification and quantification of these pyrrolo‐ and pyrido[1,2‐a]azepine derivatives in three Stemona species. The best results were obtained with a NACE‐ESI‐IT‐MS method, utilizing an electrolyte of 50 mM ammonium acetate, 1 M acetic acid and 10% methanol in ACN and a separation voltage of 30 kV. Samples were injected voltage‐assisted with 20 kV for 1 s. Isopropanol:water (1:1) was used as ESI sheath liquid at a flow rate of 3 µL/min. The assay was applied for the qualitative profiling of Stemona alkaloids in S. curtisii, S. collinsae and S. tuberosa. For unambiguous peak assignment of more than forty unidentified alkaloids MS/MS experiments were performed and fragmentation patterns studied. Subsequently the method was validated for the quantitative determination of four selected derivatives (RSD inter‐ and intraday <6%, LODs <7.5 µg/mL, LOQs <25.0 µg/mL, for all analytes, recovery rates >98.9%) in several Stemona sp. extracts.
Redistribution of archaeological assemblages in plowzones
Authors: Navazo Marta , Díez Carlos
Published: April 2008

Archaeological surface surveys have located open‐air sites on cropland in the Sierra de Atapuerca (Burgos, Spain). To what degree agricultural disturbances have impacted archaeological site integrity is poorly defined and may greatly affect interpretations of prehistoric land use. This paper presents the results of three experiments concerned with the effects of tillage on artifact distribution, focusing specifically on lateral and vertical artifact displacement. We demonstrate highly variable horizontal displacement of artifacts by plowing and overall downward movement of lithic materials within the soil. This results in an expansion of site boundaries and reduction of surface artifact density, yielding a biased and unrepresentative picture of past human activity. More experimental studies are needed to better define agricultural disturbances to surface archaeological assemblages. © 2008 Wiley Periodicals, Inc.
Geoarchaeological study of the Phoenician cemetery of Tyre‐Al Bass (Lebanon) and geomorphological evolution of a tombolo
Authors: Carmona Pilar , Ruiz José Miguel
Published: April 2008

The geoarchaeological record of the Phoenician necropolis of Al Bass (Lebanon) provides information concerning the geomorphological evolution of a late Holocene tombolo. Physical and chemical analysis of sediments indicates that the cemetery (9th century B.C.) was located near a littoral lagoon, between the dunes of a cuspate spit pointing toward the island of Tyre. From the sea apex of this spit, the moles mentioned in historical chronicles were constructed. Once mainland and island were connected, at the northern coast (where the port of Sidon was located), a sediment trap was formed, which quickly filled with silt. Afterwards, an extensive field of sand dunes buried all the archaeological remains from Phoenician to Roman times. © 2008 Wiley Periodicals, Inc.
Stratigraphic landscape analysis: Charting the Holocene movements of the Nile at Karnak through ancient Egyptian time
Authors: Bunbury J. M. , Graham A. , Hunter M. A.
Published: April 2008

Geological analysis of 5–10‐m‐long sediment cores in the context of the anthropologically derived materials within them has allowed us to identify ancient landscape features in the Theban area around Luxor, Egypt. From these observations we propose a sequence of island formation and northwestward movement of the Nile from the Middle Kingdom onward in the area of the temple complexes of Karnak. The geoarchaeological techniques used appear to document the Holocene lateral migration and vertical aggradation of the Nile. Our method can be used to test postulated movements and is applicable to sites in river or coastal plains where sediments were being deposited during the occupation of the site. The sediments were sieved to retrieve sherds and numerous other small items (2 mm and larger), which included worked stone fragments, rootlet concretions (rhizocretions), desert polished sand grains, and occasionally beads. The small stone fragments can be correlated with buildings and sherds of known age within the site, while the rhizocretions and desert sand grains indicate environmental conditions prevailing at the time of deposition. © 2008 Wiley Periodicals, Inc.
Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice
Authors: Diaz Mauricio Berriel , Krones-Herzig Anja , Metzger Dagmar , Ziegler Anja , Vegiopoulos Alexandros , Klingenspor Martin , Müller-Decker Karin , Herzig Stephan
Published: April 2008

In mammals, triglycerides (TG) represent the most concentrated form of energy. Aberrant TG storage and availability are intimately linked to the negative energy balance under severe clinical conditions, such as starvation, sepsis, or cancer cachexia. Despite its crucial role for energy homeostasis, molecular key determinants of TG metabolism remain enigmatic. Here we show that the expression of nuclear receptor cofactor receptor interacting protein (RIP) 140 was induced in livers of starved, septic, and tumor-bearing mice. Liver-specific knockdown of RIP140 led to increased hepatic TG release and alleviated hepatic steatosis in tumor-bearing, cachectic animals. Indeed, hepatic RIP140 was found to control the expression of lipid-metabolizing genes in liver.

Conclusion:

By preventing the mobilization of hepatic TG stores, the induction of RIP140 in liver provides a molecular rationale for hepatic steatosis in starvation, sepsis, or cancer cachexia. Inhibition of hepatic RIP140 transcriptional activity might, thereby, provide an attractive adjunct scheme in the treatment of these conditions. (Hepatology 2008.)
Diminished 5‐HT functioning in CBCL pediatric bipolar disorder‐profiled ADHD patients versus normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance
Authors: Zepf F. D. , Wöckel L. , Poustka F. , Holtmann M.
Published: April 2008

Objective

There is a current debate on characterizing children with pediatric bipolar disorder (PBD) through a profile within the child behaviour checklist (CBCL), and on the involvement of the 5‐HT system in the underlying neurobiological processes of PBD. The aim of the present paper was to investigate reaction time performance in patients with CBCL‐PBD and to discriminate ADHD from ADHD with CBCL‐PBD with respect to diminished 5‐HT functioning and reaction time.

Methods

Twenty‐two patients with ADHD received the rapid tryptophan depletion test (RTD) thus lowering the central‐nervous 5‐HT synthesis rate within a placebo‐controlled double‐blind within‐subject crossover design. Reaction time was assessed using a competitive reaction time game with low and high provocation after both depletion and placebo intake. The study sample was divided into high and low scorers according to their CBCL‐PBD scores.

Results

Comparing those six patients with the highest and clinically significant CBCL‐PBD scores versus those six patients with the lowest, patients with a high CBCL‐PBD score showed a slower reaction time under RTD compared to patients with low CBCL‐PBD scores after high provocation. CBCL‐‘aggression’ discriminated between the two groups.

Conclusions

The results suggest alterations in 5‐HT functioning in CBCL‐PBD‐spectrum patients, and ‘aggression’ as a potential moderator variable to ADHD. Copyright © 2008 John Wiley & Sons, Ltd.
Modelling the non‐linear hydrological behaviour of a small Mediterranean forested catchment
Authors: Medici C. , Butturini A. , Bernal S. , Vázquez E. , Sabater F. , Vélez J. I. , Francés F.
Published: April 2008

A progressive perceptual understanding approach was used to identify a model structure able to represent the non‐linear behaviour of the hydrological cycle in a small intermittent Mediterranean stream. The initial lumped model structure consisting of a series of four connected water tanks (LU3) progressed to a model with five tanks (LU4), and finally to a semidistributed model structure (SD4) in which spatial variability of the evapotranspiration according to the vegetation cover and to the local aspect was considered. In the final model structure, which gave the best fit (Nash–Sutcliffe efficiency index = 0·78), an additional tank representing the riparian zone was included (SD4‐R). Results showed that the abrupt changes of the riparian water table during summer and the formation of a perched water table during the transition from dry to wet conditions were the main mechanisms leading to the non‐linear hydrological behaviour. The transpiration process from the saturated zone and the spatial variability of evapotranspiration resulted in key factors successfully representing the annual water balance. The spatial and temporal validations carried out for each of the four model structures considered in this study supported the hypothesis adopted during the calibration process. Copyright © 2008 John Wiley & Sons, Ltd.
The influence of preferential flow on hillslope hydrology in a semi‐arid watershed (in the Spanish Dehesas)
Authors: van Schaik N. L. M. B. , Schnabel S. , Jetten V. G.
Published: April 2008

Preferential flow is known to influence hillslope hydrology in many areas around the world. Most research on preferential flow has been performed in temperate regions. Preferential infiltration has also been found in semi‐arid regions, but its impact on the hydrology of these regions is poorly known. The aim of this study is to describe and quantify the influence of preferential flow on the hillslope hydrology from small scale (infiltration) to large scale (subsurface stormflow) in a semi‐arid Dehesa landscape. Precipitation, soil moisture content, piezometric water level and discharge data were used to analyse the hydrological functioning of a catchment in Spain. Variability of soil moisture content during the transition from dry to wet season (September to November) within horizontal soil layers leads to the conclusion that there is preferential infiltration into the soils. When the rainfall intensity is high, a water level rapidly builds up in the piezometer pipes in the area, sometimes even reaching soil surface. This water level also drops back to bedrock within a few hours (under dry catchment conditions) to days (under wet catchment conditions). As the soil matrix is not necessarily wet while this water layer is built up, it is thought to be a transient water table in large connected pores which drain partly to the matrix, partly fill up bedrock irregularities and partly drain through subsurface flow to the channels. When the soil matrix becomes wetter the loss of water from macropores to the matrix and bedrock decreases and subsurface stormflow increases. It may be concluded that the hillslope hydrological system consists of a fine matrix domain and a macropore domain, which have their own flow characteristics but which also interact, depending on the soil matrix and macropore moisture contents. The macropore flow can result in subsurface flow, ranging from 13% contribution to total discharge for a large event of high intensity rainfall or high discharge to 80% of total discharge for a small event with low intensity rainfall or low discharge. During large events the fraction of subsurface stormflow in the discharge is suppressed by the large amount of surface runoff. Copyright © 2008 John Wiley & Sons, Ltd.
Isotype‐specific inhibitors of the glycolytic key regulator pyruvate kinase subtype M2 moderately decelerate tumor cell proliferation
Authors: Spoden Gilles A. , Mazurek Sybille , Morandell Dieter , Bacher Nicole , Ausserlechner Michael J. , Jansen‐Dürr Pidder , Eigenbrodt Erich , Zwerschke Werner
Published: April 2008

Tumor cells express the glycolytic regulator pyruvate kinase subtype M2 (M2‐PK), which can occur in a tetrameric form with high affinity to its substrate phosphoenolpyruvate (PEP) and a dimeric form with a low PEP affinity. The transition between both conformations contributes to the control of glycolysis and is important for tumor cell proliferation and survival. Here we targeted M2‐PK by synthetic peptide aptamers, which specifically bind to M2‐PK and shift the isoenzyme into its low affinity dimeric conformation. The aptamer‐induced dimerization and inactivation of M2‐PK led to a significant decrease in the PK mass‐action ratio as well as ATP:ADP ratio in the target cells. Furthermore, the expression of M2‐PK‐binding peptide aptamers moderately reduced the growth of immortalized NIH3T3 cell populations by decelerating cell proliferation, but without affecting apoptotic cell death. Moreover, the M2‐PK‐binding peptide aptamers also reduced the proliferation rate of human U‐2 OS osteosarcoma cells. In the present study, we developed the first specific inhibitors of the pyruvate kinase isoenzyme type M2 and present evidence that these inhibitors moderately decelerate tumor cell proliferation. © 2008 Wiley‐Liss, Inc.
Lung cancer epigenetics and genetics
Authors: Risch Angela , Plass Christoph
Published: April 2008

Lung cancer is the leading cause of cancer‐related death and thus a major health problem. The efficiency of current treatment modalities for lung cancer depends strongly on the time of diagnosis, with better chances of survival if a tumor has been detected at an early stage. Thus, there is an urgent need for rapid and efficient early detection methods. Biomarkers represent a possible alternative to current, rather expensive, screening tools such as spiral computer tomography (CT), or may allow the identification of high risk groups for whom screening would be cost efficient. Although most lung cancers are the consequence of smoking, a substantial fraction of molecular‐epidemiological studies point to high‐prevalence, low‐penetrance genetic polymorphisms as modifiers of environmental lung cancer risk. In the past the genomics field has also made significant advances in identifying genetic lesions that can now be harvested with the goal of identifying novel biomarkers for lung cancer. Furthermore, the importance of epigenetic changes that occur during lung cancer development has been reported, but has been underestimated in the past. Novel high‐throughput, quantitative assays for the detection of DNA methylation or histone tail modifications are now applied, to search for alterations in the lung cancer genome and will identify novel cancer‐related genes that may become attractive targets for treatment, provide new insight into the biology of lung cancers, and could also become useful biomarkers for the early detection of lung cancer in sputum, or may be used as prognostic markers. Thus, an integrative approach in lung cancer research combining epidemiological, genetic and epigenetic information becomes an important concept for the future. © 2008 Wiley‐Liss, Inc.
Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine
Authors: Stresemann Carlo , Lyko Frank
Published: April 2008

The cytosine analogues 5‐azacytosine (azacytidine) and 2′‐deoxy‐5‐azacytidine (decitabine) are the currently most advanced drugs for epigenetic cancer therapies. These compounds function as DNA methyltransferase inhibitors and have shown substantial potency in reactivating epigenetically silenced tumor suppressor genes in vitro. However, it has been difficult to define the mode of action of these drugs in patients and it appears that clinical responses are influenced both by epigenetic alterations and by apoptosis induction. To maximize the clinical efficacy of azacytidine and decitabine it will be important to understand the molecular changes induced by these drugs. In this review, we examine the pharmacological properties of azanucleosides and their interactions with various cellular pathways. Because azacytidine and decitabine are prodrugs, an understanding of the cellular mechanisms mediating transmembrane transport and metabolic activation will be critically important for optimizing patient responses. We also discuss the mechanism of DNA methyltransferase inhibition and emphasize the need for the identification of predictive biomarkers for the further advancement of epigenetic therapies. © 2008 Wiley‐Liss, Inc.
Histone deacetylases as transducers and targets of nuclear signaling
Authors: Walkinshaw Donald R. , Tahmasebi Soroush , Bertos Nicholas R. , Yang Xiang‐Jiao
Published: April 2008

Histone deacetylase (HDAC) activity was first discovered about 40 years ago, but it was not until the molecular identification of the first HDACs in 1996 that this family of enzymes gained prominence. In addition to histones, HDACs reverse lysine acetylation of various non‐histone proteins located in the nucleus and the cytoplasm. Here, we examine the nuclear roles of these enzymes, with a specific focus on their active crosstalk with different chromatin regulators. J. Cell. Biochem. 104: 1541–1552, 2008. © 2008 Wiley‐Liss, Inc.
Centromeres in cell division, evolution, nuclear organization and disease
Authors: Gonçalves dos Santos Silva Amanda , Sarkar Rahul , Harizanova Jana , Guffei Amanda , Mowat Michael , Garini Yuval , Mai Sabine
Published: April 2008

As the spindle fiber attachment region of the chromosome, the centromere has been investigated in a variety of contexts. Here, we will review current knowledge about this unique chromosomal region and its relevance for proper cell division, speciation, and disease. Understanding the three‐dimensional organization of centromeres in normal and tumor cells is just beginning to emerge. Multidisciplinary research will allow for new insights into its normal and aberrant nuclear organization and may allow for new therapeutic interventions that target events linked to centromere function and cell division. J. Cell. Biochem. 104: 2040–2058, 2008. © 2008 Wiley‐Liss, Inc.
Gliotoxin enhances radiotherapy via inhibition of radiation‐induced GADD45a, p38, and NFκB activation
Authors: Hur Jung‐Mu , Yun Hye‐Jeong , Yang Soo‐Hyung , Lee Woo‐Yiel , Joe Min‐ho , Kim Dongho
Published: April 2008

The purpose of the study was to elucidate the mechanism underlying the enhancement of radiosensitivity to 60Co γ‐irradiation in human hepatoma cell line HepG2 pretreated with gliotoxin. Enhancement of radiotherapy by gliotoxin was investigated in vitro with human hepatoma HepG2 cell line. Apoptosis related proteins were evaluated by Western blotting. Annexin V/PI and reactive oxygen species (ROS) were quantified by Flow Cytometric (FACS) analysis. Gliotoxin (200 ng/ml) combined with radiation (4 Gy) treated cells induced apoptosis. Cells treated with gliotoxin (200 ng/ml) prior to irradiation at 4 Gy induced the expression of bax and nitric oxide (NO). The gliotoxin‐irradiated cells also increased caspase‐3 activation and ROS. Gadd45a, p38, and nuclear factor kappa B (NFκB) activated in irradiated cells was inhibited by Gliotoxin. Specific inhibitors of p38 kinase, SB203580, significantly inhibited NFκB activation and increased the cytotoxicity effect in cells exposed to gliotoxin combined with irradiation. However, SB203580 did not suppress the activation of Gadd45a in irradiated cells. Gliotoxin inhibited anti‐apoptotic signal pathway involving the activation of Gadd45a‐p38‐NFκB mediated survival pathway that prevent radiation‐induced cell death. Therefore, gliotoxin, blocking inflammation pathway and enhancing irradiation‐induced apoptosis, is a promising agent to increase the radiotherapy of tumor cells. J. Cell. Biochem. 104: 2174–2184, 2008. © 2008 Wiley‐Liss, Inc.
Peer victimization and depression among Hong Kong adolescents
Authors: Cheng Sheung‐Tak , Cheung Kelvin C. C. , Cheung Chau‐kiu
Published: April 2008

The present study examined the gender differences in the relationship between victimization and depression, as well as in the buffering effect of social support, in Hong Kong adolescents. Based on social role theory, we predicted (a) that victimization would be associated with higher depression in boys than in girls, and (b) that social support would have a stronger buffering effect in boys than in girls. Results showed that boys reported more victimizations than girls, and victimization was slightly more strongly associated with depressive symptoms in boys than in girls. Parental support had a direct effect on depression, but no buffering effect. A buffering effect was found for friend support, but only in boys; high support from friends was associated with fewer depressive symptoms at high levels of victimization. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:766–776, 2008.
Effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia
Authors: Beeres Saskia L.M.A. , Lamb Hildo J. , Roes Stijntje D. , Holman Eduard R. , Kaandorp Theodorus A.M. , Fibbe Willem E. , de Roos Albert , van der Wall Ernst E. , Schalij Martin J. , Bax Jeroen J. , Atsma Douwe E.
Published: April 2008

Purpose

To evaluate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia.

Materials and Methods

In 24 patients (19 male; 65 ± 9 years) with refractory angina (Canadian Cardiovascular Society [CCS] class III–IV) 84.6 ± 28.7 × 106 bone marrow‐derived mononuclear cells were injected intramyocardially (using the NOGA system) in regions with ischemia on Tc‐99m tetrofosmin single photon emission computed tomography (SPECT). Diastolic function was evaluated at baseline and at three months using magnetic resonance imaging (MRI) and tissue Doppler imaging (TDI).

Results

MRI revealed an increased early (E) peak filling rate (374 ± 121 mL/second vs. 412 ± 102 mL/second; P = 0.04), whereas the atrial (A) peak filling rate remained unchanged (340 ± 81 mL/second vs. 334 ± 93 mL/second; P = not significant [NS]). The E/A peak flow ratio increased from 1.09 ± 0.33 to 1.23 ± 0.47 at three months (P = 0.02). TDI demonstrated a significant improvement in early diastolic velocity (E′) from 4.4 ± 1.7 cm/second to 4.8 ± 1.6 cm/second at three months (P = 0.03), whereas the late diastolic velocity (A′) remained unchanged (6.0 ± 1.6 cm/second vs. 6.0 ± 1.7 cm/second; P = NS). Consequently, the E′/A′ ratio increased from 0.74 ± 0.19 to 0.84 ± 0.28 at three months (P = 0.02).

Conclusion

Intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia improved MRI and TDI‐derived parameters of diastolic function. J. Magn. Reson. Imaging 2008;27:992–997. © 2008 Wiley‐Liss, Inc.
3D myocardial tissue tracking with slice followed cine DENSE MRI
Authors: Spottiswoode Bruce S. , Zhong Xiaodong , Lorenz Christine H. , Mayosi Bongani M. , Meintjes Ernesta M. , Epstein Frederick H.
Published: April 2008

Purpose

To track three‐dimensional (3D) myocardial tissue motion using slice followed cine displacement encoded imaging with stimulated echoes (DENSE).

Materials and Methods

Slice following (SF) has previously been developed for 2D myocardial tagging to compensate for the effect of through‐plane motion on 2D tissue tracking. By incorporating SF into a cine DENSE sequence, and applying displacement encoding in three orthogonal directions, we demonstrate the ability to track discrete elements of a slice of myocardium in 3D as the heart moves through the cardiac cycle. The SF cine DENSE tracking algorithm was validated on a moving phantom, and the effects of through‐plane motion on 2D cardiac strain were investigated in six healthy subjects.

Results

A through‐plane tracking accuracy of 0.46 ± 0.32 mm was measured for a typical range of myocardial motion using a rotating phantom. In vivo 3D measurements of cardiac motion were consistent with prior myocardial tagging results. Through‐plane rotation in a mid‐ventricularshort‐axis view was shown to decrease the magnitude of the 2D end‐systolic circumferential strain by 3.91 ± 0.43% and increase the corresponding radial strain by 6.01 ± 1.07%.

Conclusion

Slice followed cine DENSE provides an accurate method for 3D tissue tracking. J. Magn. Reson. Imaging 2008;27:1019–1027. © 2008 Wiley‐Liss, Inc.
Arterial spin labeling of cerebral perfusion territories using a separate labeling coil
Authors: Paiva Fernando F. , Tannús Alberto , Talagala S. Lalith , Silva Afonso C.
Published: April 2008

Purpose

To obtain cerebral perfusion territories of the left, the right, and the posterior circulation in humans with high signal‐to‐noise ratio (SNR) and robust delineation.

Materials and Methods

Continuous arterial spin labeling (CASL) was implemented using a dedicated radio frequency (RF) coil, positioned over the neck, to label the major cerebral feeding arteries in humans. Selective labeling was achieved by flow‐driven adiabatic fast passage and by tilting the longitudinal labeling gradient about the Y‐axis by θ = ± 60°.

Results

Mean cerebral blood flow (CBF) values in gray matter (GM) and white matter (WM) were 74 ± 13 mL · 100 g−1 · minute−1 and 14 ± 13 mL · 100 g−1 · minute−1, respectively (N = 14). There were no signal differences between left and right hemispheres when θ = 0° (P > 0.19), indicating efficient labeling of both hemispheres. When θ = +60°, the signal in GM on the left hemisphere, 0.07 ± 0.06%, was 92% lower than on the right hemisphere, 0.85 ± 0.30% (P < 1 × 10−9), while for θ = −60°, the signal in the right hemisphere, 0.16 ± 0.13%, was 82% lower than on the contralateral side, 0.89 ± 0.22% (P < 1 × 10−10). Similar attenuations were obtained in WM.

Conclusion

Clear delineation of the left and right cerebral perfusion territories was obtained, allowing discrimination of the anterior and posterior circulation in each hemisphere. J. Magn. Reson. Imaging 2008;27:970–977. © 2008 Wiley‐Liss, Inc.
Positive contrast MR‐lymphography using inversion recovery with ON‐resonant water suppression (IRON)
Authors: Korosoglou Grigorios , Tang Lijun , Kedziorek Dorota , Cosby Kenyatta , Gilson Wesley D. , Vonken Evert‐Jan , Schär Michael , Sosnovik David , Kraitchman Dara L. , Weiss Robert G. , Weissleder Ralf , Stuber Matthias
Published: April 2008

Purpose

To investigate the utility of inversion recovery with ON‐resonant water suppression (IRON) to create positive signal in normal lymph nodes after injection of superparamagnetic nanoparticles.

Materials and Methods

Experiments were conducted on six rabbits, which received a single bolus injection of 80 μmol Fe/kg monocrystalline iron oxide nanoparticle (MION‐47). Magnetic resonance imaging (MRI) was performed at baseline, 1 day, and 3 days after MION‐47 injection using conventional T1‐ and T2*‐weighted sequences and IRON. Contrast‐to‐noise ratios (CNR) were measured in blood and in paraaortic lymph nodes.

Results

On T2*‐weighted images, as expected, signal attenuation was observed in areas of paraaortic lymph nodes after MION‐47 injection. However, using IRON the paraaortic lymph nodes exhibited very high contrast enhancement, which remained 3 days after injection. CNR with IRON was 2.2 ± 0.8 at baseline, increased markedly 1 day after injection (23.5 ± 5.4, P < 0.01 vs. baseline), and remained high after 3 days (21.8 ± 5.7, *P < 0.01 vs. baseline). CNR was also high in blood 1 day after injection (42.7 ± 7.2 vs. 1.8 ± 0.7 at baseline, P < 0.01) but approached baseline after 3 days (1.9 ± 1.4, P = NS vs. baseline).

Conclusion

IRON in conjunction with superparamagnetic nanoparticles can be used to perform ‘positive contrast’ MR‐lymphography, particularly 3 days after injection of the contrast agent, when signal is no longer visible within blood vessels. The proposed method may have potential as an adjunct for nodal staging in cancer screening. J. Magn. Reson. Imaging 2008;27:1175–1180. © 2008 Wiley‐Liss, Inc.
A tracking‐based diffusion tensor imaging segmentation method for the detection of diffusion‐related changes of the cervical spinal cord with aging
Authors: Van Hecke Wim , Leemans Alexander , Sijbers Jan , Vandervliet Evert , Van Goethem Johan , Parizel Paul M.
Published: April 2008

Purpose

To compare region of interest (ROI)‐based and diffusion tensor tractography (DTT)‐based methods for evaluating diffusion properties of the spinal cord as a function of age.

Materials and Methods

Commonly, an ROI segmentation is used to delineate the spinal cord. In this work, new segmentation methods are developed based on DTT. In a first, DTT‐based, segmentation approach, the diffusion properties are calculated on the tracts. In a second method, the diffusion properties are analyzed in the spinal cord voxels that contain a certain number of tracts. We studied the changes in diffusion properties of the human spinal cord in subjects of different ages. Diffusion tensor imaging (DTI) measurements of the cervical spinal cord were acquired on 42 healthy volunteers (age range = 19–87 years). The fractional anisotropy (FA), the mean diffusivity (MD), and eigenvalues (λ1, λ2, and λ3) were compared for the ROI‐ and DTT‐based segmentation methods.

Results

Our automatic techniques are shown to be highly reproducible and sensitive for detecting DTI changes. FA decreased (r = –0.38; P < 0.05), whereas MD and eigenvalues increased (r = ± 0.45; P < 0.05) with age. These trends were not statistically significant for the ROI‐based segmentation (P > 0.05).

Conclusion

DTT is a robust and reproducible technique to segment the voxels of interest in the spinal cord. J. Magn. Reson. Imaging 2008;27:978–991. © 2008 Wiley‐Liss, Inc.
Diffusion‐weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft‐tissue sarcomas
Authors: Dudeck Oliver , Zeile Martin , Pink Daniel , Pech Maciej , Tunn Per‐Ulf , Reichardt Peter , Ludwig Wolf‐Dieter , Hamm Bernd
Published: April 2008

Purpose

To determine if diffusion‐weighted imaging (DWI) can be used as a surrogate marker of tumor response to anticancer therapy in patients with soft‐tissue sarcomas.

Materials and Methods

Magnetic resonance imaging (MRI) including echo‐planar DWI sequences was performed prospectively in 23 consecutive patients with soft‐tissue sarcomas before and after initiation of regional or systemic chemotherapy. The mean interval between initial and follow‐up MRI was 56.9 ± 23.2 days. Tumor volumes were determined by manual segmentation of tumor borders on contrast‐enhanced T1‐weighted images. The apparent diffusion coefficient (ADC) was calculated from corresponding sections of ADC maps on initial and follow‐up DWI. Subsequently, changes in tumor volumes and ADC were correlated using the Pearson correlation coefficient.

Results

A high degree of correlation was found when changes in tumor volumes and ADC values were compared (r = −0.925, P < 0.0001), regardless of the effectiveness of anticancer therapy expressed as changes of tumor volume.

Conclusion

DWI can be used as a supplement to morphologic imaging for the evaluation of tumor response to anticancer therapy in patients with soft‐tissue sarcomas. As cellular changes are expected to precede morphologic changes in treated tumors, DWI performed at an early stage of fractionated therapy may provide unique prognostic information of its effectiveness. J. Magn. Reson. Imaging 2008;27:1109–1113. © 2008 Wiley‐Liss, Inc.
Delayed enhancement in hypertrophic cardiomyopathy: Comparison with myocardial tagging MRI
Authors: Kim Young Jin , Choi Byoung Wook , Hur Jin , Lee Hye‐Jeong , Seo Jae Seung , Kim Tae Hoon , Choe Kyu Ok , Ha Jong‐Won
Published: April 2008

Purpose

To evaluate the relationship between delayed enhancement (DE) and regional left ventricular function in hypertrophic cardiomyopathy (HCM) using gadolinium enhancement MRI and myocardial tagging MRI.

Materials and Methods

Cine imaging, delayed enhancement imaging, and tagging MRI were performed in 25 patients with HCM. The location, pattern, and extent of DE were evaluated. Circumferential shortening (Ecc) was obtained by analyzing MR tagging images with HARP software.

Results

DE occurred in 21 (84%) patients with a high frequency of localization in the septum and the right ventricular attachment sites. Circumferential shortening was significantly decreased in the enhanced segments compared with nonenhanced segments (P < 0.0001). The myocardial wall was thicker in the enhanced segments than in the nonenhanced segments (P < 0.0001). However, circumferential shortening was significantly decreased in the enhanced segments of the same thickness (P < 0.0001). Circumferential shortening was more substantially impaired in the segments with focal nodular enhancement than those in the segments with ill‐defined patchy enhancement (P = 0.0002).

Conclusion

In HCM, DE is commonly found and circumferential shortening is significantly impaired in the regions with DE, regardless of the degree of myocardial hypertrophy. Focal nodular enhancement is particularly related with regional dysfunction in patients with HCM. J. Magn. Reson. Imaging 2008;27:1054–1060. © 2008 Wiley‐Liss, Inc.
Evaluation and adaptation of a regional climate model for the Horn of Africa: rainfall climatology and interannual variability
Authors: Segele Zewdu T. , Leslie Lance M. , Lamb Peter J.
Published: April 2008

This study evaluates the ability of the Abdus Salam International Center for Theoretical Physics (ICTP) version 3 Regional Climate Model (RegCM3) to reproduce the observed rainfall amounts and distribution over the topographically varied region of the Horn of Africa. Simulations are performed for the widespread very dry 1984 and locally very wet 1996 years using all of the alternative convective schemes available in the ICTP RegCM3. Extensive comparisons of simulations for 1984 and 1996 reveal that the Emanuel scheme best captures the rainfall patterns and interannual variations for the two extreme years over the Horn of Africa. This scheme therefore is selected for specific adaptation for the region, despite its excessive rainfall estimation there and its demonstrated deficiencies over other regions of Africa not of interest in this study.

To reduce rainfall overestimation by the Emanuel scheme, several sensitivity experiments are performed by varying the key parameters that control the rate of convective mass flux, the fraction of condensed water converted to precipitation, and the heating and moistening characteristics of the environment. Results show that the amount of condensed water that ultimately falls out as rain crucially affects simulated rainfall amounts. With an appropriate adjustment to this key parameter, the excessive rainfall amount produced by the Emanuel scheme is reduced substantially. Furthermore, evaluation of RegCM3 simulations for 1982–1999 shows that the modified Emanuel convective scheme not only reproduces the 18‐year average rainfall realistically but also captures the interannual variability adequately over the Horn of Africa. The correlation between the modified Emanuel‐simulated and Ethiopian station rainfall is quite strong (+0.66). This customized ICTP RegCM3 model now can be used with confidence for the Horn of Africa to study regional rainfall processes and variability and to dynamically downscale seasonal rainfall forecasts. Copyright © 2008 Royal Meteorological Society