bluuebunny/crossref_metadata_2025 huggingface dataset:
Complementary therapies for children undergoing stem cell transplantation
Authors: Phipps Sean , Barrera Maru , Vannatta Kathryn , Xiong Xiaoping , Doyle John J. , Alderfer Melissa A.
Published: July 2010

BACKGROUND:

Children undergoing stem cell transplant (SCT) experience high levels of somatic distress and mood disturbance. This trial evaluated the efficacy of complementary therapies (massage, humor therapy, relaxation/imagery) for reducing distress associated with pediatric SCT.

METHODS:

Across 4 sites, 178 pediatric patients scheduled to undergo SCT were randomized to a child‐targeted intervention involving massage and humor therapy, the identical child intervention plus a parent intervention involving massage and relaxation/imagery, or standard care. Randomization was stratified by site, age, and type of transplant. The interventions began at admission and continued through SCT Week +3. Primary outcomes included patient and parent reports of somatic distress and mood disturbance obtained weekly from admission through Week +6 using the Behavioral, Affective, and Somatic Experiences Scales. Secondary outcomes included length of hospitalization, time to engraftment, and usage of narcotic analgesic and antiemetic medications.

RESULTS:

A mixed model approach was used to assess longitudinal trends of patient and parent report outcomes and to test differences between groups on these measures. Significant changes across time were observed on all patient and parent report outcomes. However, no significant differences between treatment arms were found on the primary outcomes. Similarly, no significant between‐group differences were noted on any of the medical variables as secondary outcomes.

CONCLUSIONS:

Results of this multisite trial failed to document significant benefits of complementary interventions in the pediatric SCT setting. Cancer 2010. © 2010 American Cancer Society.
The tyrosine kinase c‐Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors
Authors: Koos Björn , Jeibmann Astrid , Lünenbürger Henning , Mertsch Sonja , Nupponen Nina N. , Roselli Annariikka , Leuschner Ivo , Paulus Werner , Frühwald Michael C. , Hasselblatt Martin
Published: July 2010

BACKGROUND:

Atypical teratoid/rhaboid tumors (AT/RTs) and extracranial malignant rhabdoid tumors are highly malignant neoplasms with a dismal prognosis. These tumors predominantly affect infants and targeted, adjuvant treatment approaches would be highly desirable.

METHODS:

In the current study, the authors investigated the expression and functional role of tyrosine kinases in 2 malignant rhabdoid tumor cell lines (A204 and G401) and in a series of 5 AT/RTs and 18 malignant rhabdoid tumors (13 rhabdoid tumors of the kidney and 5 extrarenal rhabdoid tumors).

RESULTS:

Both cell lines consistently expressed the tyrosine kinase c‐Abl, which promoted proliferation as assessed by small interfering RNA knockdown. Blockage of c‐Abl using the tyrosine kinase inhibitor imatinib resulted in reduced cellular growth in both cell lines. Furthermore, c‐Abl was expressed in all rhabdoid tumors, whereas expression of platelet‐derived growth factor receptor subtypes alpha and beta was infrequent and c‐Kit expression was absent.

CONCLUSIONS:

The current data pointed toward a role for c‐Abl in the biology of malignant rhabdoid tumors and provided a rationale for the investigation of tyrosine kinase inhibitors that target c‐Abl for the treatment of these aggressive tumors. Cancer 2010. © 2010 American Cancer Society
Dasatinib induces autophagic cell death in human ovarian cancer
Authors: Le Xiao‐Feng , Mao Weiqun , Lu Zhen , Carter Bing Z. , Bast Robert C.
Published: July 2010

BACKGROUND:

Dasatinib, an inhibitor of Src/Abl family kinases, can inhibit tumor growth of several solid tumors. However, the effect and mechanism of action of dasatinib in human ovarian cancer cells remains unknown.

METHODS:

Dasatinib‐induced autophagy was determined by acridine orange staining, punctate localization of GFP‐LC3, LC3 protein blotting, and electron microscopy. Significance of beclin 1, AKT, and Bcl‐2 in dasatinib‐induced autophagy and growth inhibition was assayed by small interfering RNA (siRNA) silencing and/or overexpression of the gene of interest.

RESULTS:

Dasatinib inhibited cell growth by inducing little apoptosis, but substantial autophagy in SKOv3 and HEY ovarian cancer cells. In vivo studies showed dasatinib inhibited tumor growth and induced both autophagy and apoptosis in a HEY xenograft model. Knockdown of beclin 1 and Atg12 expression with their respective siRNAs diminished dasatinib‐induced autophagy, whereas knockdown of p27Kip1 with specific siRNAs did not. Small hairpin RNA knockdown of beclin 1 expression reduced dasatinib‐induced autophagy and growth inhibition. Dasatinib reduced the phosphorylation of AKT, mTOR, p70S6K, and S6 kinase expression. Constitutive expression of AKT1 and AKT2 inhibited dasatinib‐induced autophagy in both HEY and SKOv3 cells. Dasatinib also reduced Bcl‐2 expression and activity. Overexpression of Bcl‐2 partially prevented dasatinib‐induced autophagy.

CONCLUSIONS:

Dasatinib induces autophagic cell death in ovarian cancer that partially depends on beclin 1, AKT, and Bcl‐2. These results may have implications for clinical use of dasatinib. Cancer 2010. © 2010 American Cancer Society.
Critical role of surgery in patients with gastroesophageal carcinoma with a poor prognosis after chemoradiation as defined by positron emission tomography
Authors: Patnana Srikrishna V. , Murthy Santosh B. , Xiao Lianchun , Rohren Eric , Hofstetter Wayne L. , Swisher Stephen G. , Liao Zhongxing , Lee Jeffrey H. , Bhutani Manoop S. , Macapinlac Homer A. , Wang Xuemei , Ajani Jaffer A.
Published: July 2010

BACKGROUND:

The prognosis of patients with localized gastroesophageal carcinoma (LGC) can be defined after chemoradiation by the standardized uptake value (SUV) of positron emission tomography (PET). High SUV (HSUV) after chemoradiation portends a poor prognosis. The authors retrospectively examined the role of surgery in patients with HSUV after chemoradiation.

METHODS:

The authors analyzed the postchemoradiation PET scans of 204 LGC patients. One hundred twenty‐nine patients had HSUV. Two postchemoradiation variables were evaluated: SUV and surgery and their association with overall survival (OS) and event‐free survival (EFS). The log‐rank test, multivariate Cox proportional hazards model, and Kaplan‐Meier survival plots were used to assess the association between OS or EFS and the dichotomized SUV (using the median SUV as the cutoff) and surgery.

RESULTS:

The median SUV was 4.6. The OS of the 52 patients who had an SUV above the median and did not undergo surgery (HSUV‐NS) (median OS, 1.22 years; 95% confidence interval [95% CI], 1.02‐2.16 years) was much shorter than that of the 77 patients with an SUV above the median who underwent surgery (HSUV‐S) (median OS, 2.7 years; 95% CI, 2.43 years to not reached [P<.0001]). Similarly, the EFS for patients with HSUV‐NS was significantly shorter than that for patients with HSUV‐S (P= .001). In the multivariate analyses, patients who underwent surgery (irrespective of SUV) had a lower risk of death (P= .0001) and disease progression (P= .002).

CONCLUSIONS:

The data from the current study suggest that surgery may prolong OS and EFS in patients with a poor prognosis after chemoradiation as defined by PET. However, these data need confirmation. Cancer 2010. © 2010 American Cancer Society.
Breastfeeding in survivors of Hodgkin lymphoma treated with chest radiotherapy
Authors: McCullough Laura , Ng Andrea , Najita Julie , Janov Abbe , Henderson Tara , Mauch Peter , Diller Lisa
Published: July 2010

BACKGROUND:

Female survivors of therapeutic chest radiation often question whether they will have difficulty with breast feeding, given their prior exposure to breast radiation. In the current study, the rates of successful breastfeeding in long‐term survivors who received chest radiotherapy (CXRT) as a treatment for Hodgkin lymphoma (HL) were examined.

METHODS:

A survey study of survivors of HL who were treated at the Joint Center for Radiation Therapy in Boston from 1969 through 1996 was performed. Patients were queried about childbearing and breastfeeding. The authors analyzed self‐reported breastfeeding success in women who reported live births after CXRT and compared them with a sibling control group.

RESULTS:

Overall, 83 female survivors of HL who were treated with CXRT reported at least 1 birth after treatment. There were a total of 141 post‐HL pregnancies resulting in births. In these women, the median age at the time of the HL diagnosis was 23 years (range, 14‐40 years) and the median radiation dose was 41 grays (Gy) (range, 27‐46 Gy). For survivors, 57 of the 94 (61%) breastfeeding attempts were successful, whereas within the control group, 74 of the 94 (79%) attempts were successful (P = .044). Accounting for maternal age at first birth and birth era, multivariable analysis suggested that HL survivors treated with CXRT may be less likely to breastfeed successfully than their siblings (odds ratio, 0.42; 95% confidence interval, 0.2‐1.0 [P = .06]).

CONCLUSIONS:

The majority of female HL survivors who were treated with CXRT report being able to breastfeed successfully. However, the results of the current study indicate a trend toward less successful breastfeeding in survivors as a previously unreported late effect of radiation. Cancer 2010. © 2010 American Cancer Society.
The 2006 consensus guidelines for the management of women with abnormal cervical screening tests
Authors: Colgan Terence J.
Published: July 2010

The American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for the management of women with abnormal cervical screening test results is a powerful, evidence‐based document representing an advance in the consistent treatment of women with cervical abnormalities. Nevertheless, the complexity of the guidelines is an outstanding issue, compliance with the guidelines is problematic in some areas, and there is a growing recognition of the deficiencies of colposcopy. In light of these challenges, the cytopathology community has an opportunity to play an active role in integrating data, defining risk, and recommending proper management for women screened for cervical cancer. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Molecular regulation of the developing commissural plate
Authors: Moldrich Randal X. , Gobius Ilan , Pollak Thomas , Zhang Jiangyang , Ren Tianbo , Brown Lucia , Mori Susumu , De Juan Romero Camino , Britanova Olga , Tarabykin Victor , Richards Linda J.
Published: July 2010

The commissural plate of the developing mouse brain showing all telencephalic midline commissures in single plane of tissue. The Journal of Comparative Neurology, Volume 518, Number 18, 3645–3661.
NIC‐assisted cache‐efficient receive stack for message passing over Ethernet
Authors: Goglin Brice
Published: July 2010

High‐speed networking in clusters usually relies on advanced hardware features in the NICs, such as zero‐copy capability. Open‐MX is a high‐performance message‐passing stack tailored for regular Ethernet hardware without such capabilities. We present the addition of a multiqueue support in the Open‐MX receive stack so that all incoming packets for the same process are handled on the same core. We then introduce the idea of binding the target end process near its dedicated receive queue. This model leads to a more cache‐efficient receive stack for Open‐MX. It also proves that very simple and stateless hardware features may have a significant impact on message‐passing performance over Ethernet. The implementation of this model in a firmware reveals that it may not be as efficient as some manually tuned micro‐benchmarks. But our multiqueue receive stack generally performs better than the original single queue stack, especially on large communication patterns where multiple processes are involved and manual binding is difficult. Copyright © 2010 John Wiley & Sons, Ltd.
On the Reliability of the AMBER Force Field and its Empirical Dispersion Contribution for the Description of Noncovalent Complexes
Authors: Kolář Michal , Berka Karel , Jurečka Petr , Hobza Pavel
Published: July 2010

The reliability of the AMBER force field is tested by comparing the total interaction energy and dispersion energy with the reference data obtained at the density functional theory–symmetry‐adapted perturbation treatment (DFT–SAPT)/aug‐cc‐pVDZ level. The comparison is made for 194 different geometries of noncovalent complexes (H‐bonded, stacked, mixed, and dispersion‐bound), at the equilibrium distances as well as at longer distances (up to a relative distance of two). The total interaction energies agree very well with the reference data and only the strength of H‐bonded complexes is slightly underestimated. In the case of dispersion energy, the overall agreement is even better, with the exception of the stacked aromatic systems, where the empirical dispersion energy is overestimated. The use of AMBER interaction energy and AMBER dispersion energy for different types of noncovalent complexes at equilibrium as well as at longer distances is thus justified, except for a few cases, such as the water molecule, where the dispersion energy is highly inaccurate.
Ion Interactions with the Carbon Nanotube Surface in Aqueous Solutions: Understanding the Molecular Mechanisms
Authors: Frolov Andrey I. , Rozhin Alex G. , Fedorov Maxim V.
Published: July 2010

We study the molecular mechanisms of alkali halide ion interactions with the single‐wall carbon nanotube surface in water by means of fully atomistic molecular dynamics simulations. We focus on the basic physical‐chemical principles of ion–nanotube interactions in aqueous solutions and discuss them in light of recent experimental findings on selective ion effects on carbon nanotubes.
Room‐temperature synthesis and characterization of cross‐like Pr2(C2O4)3·10H2O micro‐particles
Authors: Yin Xiaobin , Zhang Youjin , Fang Zhiyong , Xu Zhenyu , Zhu Wei , He Hongmei
Published: July 2010

Cross‐like Pr2(C2O4)3·10H2O micro‐particles were synthesized through a simple precipitation method at room temperature. The products were characterized by X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), field‐emission scanning electron microscopy (FESEM), thermogravimetry–differential thermal analysis (TG‐DTA) and photoluminescence (PL). The possible formation mechanism of the cross‐like Pr2(C2O4)3·10H2O micro‐particles was discussed, and Pr6O11 with similar morphology was obtained by calcining the oxalate precursor. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Transformation of a zinc inclusion complex to wurtzite ZnS microflowers under solvothermal conditions
Authors: Mi Liwei , Han Minle , Li Zhen , Wang Yaming , Shen Changyu , Zheng Zhi
Published: July 2010

Wurtzite zinc sulfide (ZnS) microflowers were synthesized successfully by a convenient solvothermal route in ethylene glycol (EG) and ethylenediamine (EN) using thiourea and zinc inclusion complex as starting materials. The inclusion complex {[Zn(bipy)2(H2O)2](4‐Cl‐3‐NH2‐C6H3SO3)2(bipy) (H2O)2}n was achieved by the reaction of zinc oxide (ZnO) and 4‐Cl‐3‐NH2‐C6H3SO3 with the bridging ligand bipy under moderate conditions, in which bipy is 4,4′‐bipyridine and 4‐Cl‐3‐NH2C6H3SO3NH is 4‐Chloro‐3‐aminobenzene sulfonic acid. The phase purity of bulk products was confirmed by powder X‐ray diffraction and element analysis. The factors that might affect the purity of the ZnS product during the synthesis were discussed in detail. It was found that the products were significantly affected by the mixed solvents and the starting materials. X‐ray single crystal diffraction, scanning electron microscopy (SEM), energy‐dispersive X‐ray spectrometry (EDS), and X‐ray diffraction (XRD) were used to characterize the products. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An improved technique for calculating relative response in cellular proliferation experiments
Authors: Munson Mark E.
Published: July 2010

Investigating the response of cells to specific agonists may involve the use of cell tracking dyes to assess the extent of stimulated proliferation, frequently reported as the proliferation index (PI). Calculation of PI uses a model for cell division that expects the cell number to double as cells proliferate through each successive generation. It is often useful to compare the PI of a stimulated control population with that of a population in the presence of some agent, whether chemical, pharmacologic, or cellular. For such comparison studies, the nature of the metric being used must be taken into account to accurately assess the extent of inhibition. Specifically, the metric used in ModFit LT (Verity Software House, Topsham, ME) and in FCS Express (De Novo Software, Los Angeles, CA) uses a metric with a lower limit of unity, whereas the metric used in FlowJo (Treestar, Ashland, OR) has a lower limit of zero. For studies involving cell proliferation comparisons using tracking dye dilution, a new equation is proposed as the appropriate calculation to use when determining the percent of relative response based on proliferation index values for a metric whose lower limit is unity.
Using surface plasmon resonance imaging to probe dynamic interactions between cells and extracellular matrix
Authors: Peterson Alexander W. , Halter Michael , Tona Alessandro , Bhadriraju Kiran , Plant Anne L.
Published: July 2010

Spatially resolved details of the interactions of cells with a fibronectin modified surface were examined using surface plasmon resonance imaging (SPRI). SPRI is a label‐free technique that is based on the spatial measurement of interfacial refractive index. SPRI is sensitive to short range interactions between cells and their substratum. The high contrast in SPR signal between cell edges and substratum facilitates identification of cell edges and segmentation of cell areas. With this novel technique, we demonstrate visualization of cell‐substratum interactions, and how cell‐substratum interactions change over time as cells spread, migrate, and undergo membrane ruffling. Published 2010 Wiley‐Liss, Inc.
Correlation analysis of intracellular and secreted cytokines via the generalized integrated mean fluorescence intensity
Authors: Shooshtari Parisa , Fortuno Edgardo S. , Blimkie Darren , Yu Miao , Gupta Arvind , Kollmann Tobias R. , Brinkman Ryan R.
Published: July 2010

The immune response in humans is usually assessed using immunogenicity assays to provide biomarkers as correlates of protection (CoP). Flow cytometry is the assay of choice to measure intracellular cytokine staining (ICS) of cell‐mediated immune (CMI) biomarkers. For CMI analysis, the integrated mean fluorescence intensity (iMFI) was introduced as a metric to represent the total functional CMI response as a CoP. iMFI is computed by multiplying the relative frequency (percent positive) of cells expressing a particular cytokine with the MFI of that population, and correlates better with protection in challenge models than either the percentage or the MFI of the cytokine‐positive population. While determination of the iMFI as a CoP can readily be accomplished in animal models that allow challenge/protection experiments, this is not feasible in humans for ethical reasons. As a first step toward extending the iMFI concept to humans, we investigated the correlation of the iMFI derived from a human innate immune response ICS assay with functional cytokine release into the culture supernatant, as innate cytokines need to be released to have a functional impact. Next, we developed a quantitatively more correlative mathematical approach for calculating the functional response of cytokine‐producing cells by incorporating the assignment of different weights to the magnitude (frequency of cytokine‐positive cells) and the quality (the MFI) of the observed innate immune response. We refer to this model as generalized iMFI. © 2010 International Society for Advancement of Cytometry
Cryptanalysis of a simple three‐party password‐based key exchange protocol
Authors: Yoon Eun‐Jun , Yoo Kee‐Young
Published: July 2010

In order to secure communications between two clients with a trusted server's help in public network environments, a three‐party authenticated key exchange (3PAKE) protocol is used to provide the transaction confidentiality and the efficiency. In 2009, Huang proposed a simple three‐party password‐based authenticated key exchange (HS‐3PAKE) protocol without any server's public key. By analysis, Huang claimed that the proposed HS‐3PAKE protocol is not only secure against various attacks, but also more efficient than previously proposed 3PAKE protocols. However, this paper demonstrates that HS‐3PAKE protocol is vulnerable to undetectable online password guessing attacks and off‐line password guessing attacks by any other user. Copyright © 2010 John Wiley & Sons, Ltd.
Deficits in sensitivity to spacing after early visual deprivation in humans: A comparison of human faces, monkey faces, and houses
Authors: Robbins Rachel A. , Nishimura Mayu , Mondloch Catherine J. , Lewis Terri L. , Maurer Daphne
Published: July 2010

Early visual deprivation caused by bilateral congenital cataracts produces deficits in discriminating faces that differ in the spacing of features, but not in feature shape (Le Grand et al. [2001] Nature 410: 810). We investigated whether these deficits are specific to human faces by testing patients' ability to discriminate between stimuli differing only in feature spacing in human and monkey faces (Experiment 1) and in houses (Experiment 2). Patients, as a group, showed deficits on only one task: they had lower accuracy than normal in discriminating feature spacing in human faces. In contrast, they were normal in discriminating feature spacing in monkey faces and in houses. The results suggest that early visual experience is necessary to set up (or preserve) the neural architecture used for processing human faces, but not for processing objects in general. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 775–781, 2010.
Photoperiodic differences in a forebrain nucleus involved in vocal plasticity: Enkephalin immunoreactivity reveals volumetric variation in song nucleus lMAN but not NIf in male European starlings (Sturnus vulgaris)
Authors: Stevenson Tyler J. , Ball Gregory F.
Published: July 2010

Seasonal variation in the volume of various song control nuclei in many passerine species remains one of the best examples of naturally occurring adult neuroplasticity among vertebrates. The lateral portion of the magnocellular nucleus of the anterior nidopallium (lMAN) is a song nucleus that is important for song learning and seems to be critical for inducing variability in the song structure that is later pruned via a feedback process to produce adult crystallized song. To date, lMAN has not been shown to exhibit seasonal changes in volume, probably because it is difficult to resolve the boundaries of lMAN when employing histological methods based on Nissl staining. Here, lMANcorevolumes were examined in intact photostimulated (i.e., breeding), castrated photostimulated and photorefractory (i.e., nonbreeding) male starlings (Sturnus vulgaris) to investigate the degree of seasonal variation in brain morphology. We present data demonstrating that the volumes of the total MAN and lMANcoredelineated by enkephalin immunoreactivity are greater in photostimulated male starlings as compared to photorefractory males. Moreover, two other regions associated with the song system that have not been investigated previously in the context of seasonal plasticity namely (i) the medial portion of MAN (mMAN), and (ii) the nucleus interfacialis (NIf) did not display significant volumetric variation. We propose that greater lMANcorevolumes are associated with the increase in vocal plasticity that is generally observed prior to production of stereotyped song. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 751–763, 2010
Developmental changes in neural corticosteroid receptor binding capacity in altricial nestlings
Authors: Wada Haruka , Breuner Creagh W.
Published: July 2010

Altricial nestlings typically do not show an adrenocortical response during the early post‐hatch period. This may be a result of an immature hypothalamic‐pituitary‐adrenal axis, or an enhanced control of the axis by negative feedback. To examine whether the dampened adrenocortical response is due to higher receptor densities in hypothalamus and hippocampus, the major sites for negative feedback and tonic inhibition, we explored the ontogenetic changes in glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities in the brain of white‐crowned sparrow nestlings. During the 10‐day nestling period, MR binding capacity decreased with age, whereas GR capacity was not affected. In addition, this overall decline in MR levels was driven entirely by a decline in cerebellar MR. No age‐related changes were observed in hippocampal or hypothalamic areas. Our findings suggest that enhanced negative feedback does not play a major role in the attenuated adrenocortical responses seen in white‐crowned sparrow nestlings. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 853–861, 2010
Immature astrocytes promote CNS axonal regeneration when combined with chondroitinase ABC
Authors: Filous Angela R. , Miller Jared H. , Coulson‐Thomas Yvette M. , Horn Kevin P. , Alilain Warren J. , Silver Jerry
Published: July 2010

Regeneration of injured adult CNS axons is inhibited by formation of a glial scar. Immature astrocytes are able to support robust neurite outgrowth and reduce scarring, therefore, we tested whether these cells would have this effect if transplanted into brain injuries. Utilizing an in vitro spot gradient model that recreates the strongly inhibitory proteoglycan environment of the glial scar we found that, alone, immature, but not mature, astrocytes had a limited ability to form bridges across the most inhibitory outer rim. In turn, the astrocyte bridges could promote adult sensory axon re‐growth across the gradient. The use of selective enzyme inhibitors revealed that MMP‐2 enables immature astrocytes to cross the proteoglycan rim. The bridge‐building process and axon regeneration across the immature glial bridges were greatly enhanced by chondroitinase ABC pretreatment of the spots. We used microlesions in the cingulum of the adult rat brains to test the ability of matrix modification and immature astrocytes to form a bridge for axon regeneration in vivo. Injured axons were visualized via p75 immunolabeling and the extent to which these axons regenerated was quantified. Immature astrocytes coinjected with chondroitinase ABC‐induced axonal regeneration beyond the distal edge of the lesion. However, when used alone, neither treatment was capable of promoting axonal regeneration. Our findings indicate that when faced with a minimal lesion, neurons of the basal forebrain can regenerate in the presence of a proper bridge across the lesion and when levels of chondroitin sulfate proteoglycans (CSPGs) in the glial scar are reduced. © 2010 Wiley Periodicals, Inc.Develop Neurobiol 70: 826–841, 2010
In vitro and in vivo characterization of Caenorhabditis elegans PHA‐4/FoxA response elements
Authors: Raharjo Wahyu Hendrati , Logan Brittany C. , Wen Shoubin , Kalb John M. , Gaudet Jeb
Published: July 2010

Caenorhabditis elegans PHA‐4 is a member of the FoxA group of transcription factors. PHA‐4 is critical for development of the C. elegans pharynx and directly regulates most or all pharyngeal genes. The consensus binding site of PHA‐4 has not been identified, with previous analysis of PHA‐4 targets relying on the mammalian FoxA consensus. Here, we use in vitro and in vivo analyses to demonstrate three features of PHA‐4 response elements. First, the PHA‐4 consensus matches that of other FoxA proteins, but only a subset of possible sites is active in an in vivo assay. Second, sequence flanking the core PHA‐4 site can influence the strength of reporter expression in vivo, as seen for other Fox proteins. Third, in the context of some pharyngeal promoters, PHA‐4 response elements are flanked by distinct cis‐regulatory elements that modulate response to PHA‐4, generating gene expression in specific pharyngeal cell types. Developmental Dynamics 239:NA–NA, 2010. © 2010 Wiley‐Liss, Inc.
Inducible lineage tracing of Pax7‐descendant cells reveals embryonic origin of adult satellite cells
Authors: Lepper Christoph , Fan Chen‐Ming
Published: July 2010

Descendants of E9.5 Pax7‐expressing (in red, β‐gal+) central dermomyotome cells contribute to myofibers (in green, MF‐20+, a myosin heavy chain protein) in the E16.5 mouse embryo. Nuclei are blue (DAPI). The β‐gal+/MF‐20_ cells that are intermingled with myofibers are likely myogenic progenitors. See the article by Lepper and Fan in this issue.
Simulation in maize–water relations: a case study for continental climate (Hungary)
Authors: Anda Angela , Dióssy László
Published: July 2010

Local consequences of the global climate change in the Carpathian Basin were followed on the basis of simulated stomatal resistances. The Crop Microclimate Simulation Model of Goudriaan was applied in our study. The expected weather, plant and soil modifications were based on long‐term observations during the time period 1961–1990 in the Keszthely area (Hungary, N 46°44′, E 17°14′; altitude 112 m). Besides application of the A2 and B2 SRES scenarios, the impact of extreme hot days was also included in the study. This was necessary as these events have recently occurred more and more frequently. Demonstration of weather scenarios with relatively high warming rates was made possible by the high resolution of the model, simulating even daily changes. The stomatal resistance significantly increased in all scenarios, as was indeed experienced in the last decade (1997–2006). A twofold increase in CO2 concentration approximately halves stomatal openings even under unchanged weather conditions. This can be considered as an advantageous side effect of the global climate change on the plant's water balance, important in continental climate because of scarce precipitation. In Scenarios A2 and B2, increases in resistance were close to the effect of doubled CO2 concentration. Surprisingly, the effect of an increase in the number of extreme hot days on stomatal resistance was moderate, below than what might have been expected. The common impact of the environmental and biological factors on stomatal resistance was realized using normalized leaf area indices, where the highest increases were predicted by using the hottest and driest scenario. Moderate changes in water loss and photosynthesis indicated a certain amount of available soil moisture reserve even in the extreme weather situations in July, at Keszthely. Decrease in carbon assimilation can occur in days with extreme temperatures. Our scenarios do not include significant precipitation decline because of forecast uncertainties. A significant precipitation decrease would fundamentally reshape our results, so we do not propose to extend our conclusions in the case of significant modification in rainfall amount or distribution. Copyright © 2010 John Wiley & Sons, Ltd.
Glycosylation contributes to variability in expression of murine cytomegalovirus m157 and enhances stability of interaction with the NK‐cell receptor Ly49H
Authors: Guseva Natalya V. , Fullenkamp Colleen A. , Naumann Paul W. , Shey Michael R. , Ballas Zuhair K. , Houtman Jon C. D. , Forbes Catherine A. , Scalzo Anthony A. , Heusel Jonathan W.
Published: July 2010

NK cell‐mediated resistance to murine cytomegalovirus (MCMV) is controlled by allelic Ly49 receptors, including activating Ly49H (C57BL/6 strain) and inhibitory Ly49I (129 strain), which specifically recognize MCMV m157, a glycosylphosphatidylinositol‐linked protein with homology to MHC class I. Although the Ly49 receptors retain significant homology to classic carbohydrate‐binding lectins, the role of glycosylation in ligand binding is unclear. Herein, we show that m157 is expressed in multiple, differentially N‐glycosylated isoforms in m157‐transduced or MCMV‐infected cells. We used site‐directed mutagenesis to express single and combinatorial asparagine (N)‐to‐glutamine (Q) mutations at N178, N187, N213, and N267 in myeloid and fibroblast cell lines. Progressive loss of N‐linked glycans led to a significant reduction of total cellular m157 abundance, although all variably glycosylated m157 isoforms were expressed at the cell surface and retained the capacity to activate Ly49HB6 and Ly49I129 reporter cells and Ly49H+ NK cells. However, the complete lack of N‐linked glycans on m157 destabilized the m157‐Ly49H interaction and prevented physical transfer of m157 to Ly49H‐expressing cells. Thus, glycosylation on m157 enhances expression and binding to Ly49H, factors that may impact the interaction between NK cells and MCMV in vivo where receptor–ligand interactions are more limiting.
Allergen‐specific naïve and memory CD4+ T cells exhibit functional and phenotypic differences between individuals with or without allergy
Authors: Kinnunen Tuure , Nieminen Anssi , Kwok William W. , Närvänen Ale , Rytkönen‐Nissinen Marja , Saarelainen Soili , Taivainen Antti , Virtanen Tuomas
Published: July 2010

Although allergen‐specific CD4+ T cells are detectable in the peripheral blood of both individuals with or without allergy, their frequencies and phenotypes within the memory as well as naïve repertoires are incompletely known. Here, we analyzed the DRB1*0401‐restricted responses of peripheral blood‐derived memory (CD4+CD45RO+) and naïve (CD4+CD45RA+) T cells from subjects with or without allergy against the immunodominant epitope of the major cow dander allergen Bos d 2 by HLA class II tetramers in vitro. The frequency of Bos d 2127–142‐specific memory T cells in the peripheral blood‐derived cultures appeared to be higher in subjects with allergy than those without, whereas naïve Bos d 2127–142‐specific T cells were detectable in the cultures of both groups at nearly the same frequency. Surprisingly, the TCR avidity of Bos d 2127–142‐specific T cells of naïve origin, as assessed by the intensity of HLA class II tetramer staining, was found to be higher in individuals with allergy. Upon restimulation, long‐term Bos d 2127–142‐specific T‐cell lines generated from both memory and naïve T‐cell pools from individuals with allergy proliferated more strongly, produced more IL‐4 and IL‐10, and expressed higher levels of CD25 but lower levels of CXCR3 than the T‐cell lines from individuals without allergy, demonstrating differences also at the functional level. Collectively, our current results suggest that not only the memory but also the naïve allergen‐specific T‐cell repertoires differ between individuals with or without allergy.
HCV‐specific T cells in HCV/HIV co‐infection show elevated frequencies of dual Tim‐3/PD‐1 expression that correlate with liver disease progression
Authors: Vali Bahareh , Jones R. Brad , Sakhdari Ali , Sheth Prameet M. , Clayton Kiera , Yue Feng‐Yun , Gyenes Gabor , Wong David , Klein Marina B. , Saeed Sahar , Benko Erika , Kovacs Colin , Kaul Rupert , Ostrowski Mario A.
Published: July 2010

Co‐infection of HCV with HIV has been associated with more rapid progression of HCV‐related disease. HCV‐specific T‐cell immune responses, which are essential for disease control, are attenuated in co‐infection with HIV. T‐cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death‐1 (PD‐1) and T‐cell immunoglobulin and mucin domain‐containing molecule‐3 (Tim‐3) expression in T‐cell exhaustion during HCV/HIV co‐infection. We show that in HCV/HIV co‐infection, both total and HCV‐specific T cells co‐express Tim‐3 and PD‐1 in significantly higher frequencies, compared with HCV mono‐infection. Co‐expression of these two markers on HCV‐specific CD8+ T cells positively correlated with a clinical parameter of liver disease progression. HCV‐specific CD8+ T cells showed greater frequencies of Tim‐3/PD‐1 co‐expression than HIV‐specific CD8+ T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim‐3 or PD‐1 pathways restored both HIV‐ and HCV‐specific CD8+ T‐cell expansion in the blood of co‐infected individuals. These data demonstrate that co‐expression of Tim‐3 and PD‐1 may play a significant role in HCV‐specific T‐cell dysfunction, especially in the setting of HIV co‐infection.
Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells
Authors: Ramirez Jean‐Marie , Brembilla Nicolò C. , Sorg Olivier , Chicheportiche Rachel , Matthes Thomas , Dayer Jean‐Michel , Saurat Jean‐Hilaire , Roosnek Eddy , Chizzolini Carlo
Published: July 2010

Ligands of the aryl hydrocarbon receptor (AHR), a transcription factor mediating the effects of dioxin, favor Th17 differentiation and exacerbate autoimmunity in mice. We investigated how AHR ligands affected human T‐cell polarization. We found that the high affinity and stable AHR‐ligand dioxin as well as the natural AHR‐ligand 6‐formylinolo[3,2‐b] carbazole induced the downstream AHR‐target cytochrome P450A1, and without affecting IFN‐γ, they enhanced IL‐22 while simultaneously decreasing IL‐17A production by CD4+ T cells. The specific AHR‐inhibitor CH‐223191 abolished these effects. Furthermore, blockade of IL‐23 and IL‐1, important for Th17 expansion, profoundly decreased IL‐17A but not IL‐22 production. AHR agonists reduced the expression of the Th17 master transcription factor retinoic acid‐related orphan receptor C (RORC), without affecting T‐bet, GATA‐3 and Foxp3. They also decreased the expression of the IL‐23 receptor. Importantly, AHR‐ligation did not only decrease the number of Th17 cells but also primed naïve CD4+ T cells to produce IL‐22 without IL‐17 and IFN‐γ. Furthermore, IL‐22 single producers did not express CD161, which distinguished them from the CD161+ Th17 cells. Hence, our data provide compelling evidence that AHR activation participates in shaping human CD4+ T‐cell polarization favoring the emergence of a distinct subset of IL‐22‐producing cells that are independent from the Th17 lineage.
Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells
Authors: Kersseboom Rogier , Kil Laurens , Flierman Roelof , van der Zee Marten , Dingjan Gemma M. , Middendorp Sabine , Maas Alex , Hendriks Rudi W.
Published: July 2010

B‐cell receptor (BCR)‐mediated signals provide the basis for B‐cell differentiation in the BM and subsequently into follicular, marginal zone, or B‐1 B‐cell subsets. We have previously shown that B‐cell‐specific expression of the constitutive active E41K mutant of the BCR‐associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low‐level expression of the E41K or E41K‐Y223F Btk mutants was associated with reduced follicular B‐cell numbers and significantly increased proportions of B‐1 cells in the spleen. Crosses with 3‐83μδ and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B‐1 B‐cell fate choice, but resulted in selective expansion or survival of B‐1 cells. Residual B cells were hyperresponsive and manifested sustained Ca2+ mobilization. They were spontaneously driven into germinal center‐independent plasma cell differentiation, as evidenced by increased numbers of IgM+ plasma cells in spleen and BM and significantly elevated serum IgM. Because anti‐nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes defective B‐cell tolerance, emphasizing that Btk signals are essential for appropriate regulation of B‐cell activation.
Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha
Authors: Mönnich Maren , Hess Isabell , Wiest Waltraud , Bachrati Csanad , Hickson Ian D. , Schorpp Michael , Boehm Thomas
Published: July 2010

All organisms possess at least one type IA DNA topoisomerase. These topoisomerases function as part of a DNA structure‐specific “dissolvasome,” also known as the RTR complex, which has critical functions in faithful DNA replication, recombination, and chromosome segregation. In humans, the heteromeric RTR complex consists of RMI1, RMI2, the Bloom's syndrome gene product (BLM), and topoisomerase 3A (TOP3A) proteins. Here, we describe the identification and characterization of two deleterious mutations in the zebrafish top3a gene that reveal an unexpected tissue‐specific requirement of top3a function in developing thymocytes. Deficiency in top3a activates a p53‐dependent check‐point but does not affect VDJ recombination. Our results suggest that TOP3A could be a candidate gene involved in human primary immunodeficiency syndromes.
Convergent pathways of macrophage polarization: The role of B cells
Authors: Sica Antonio , Porta Chiara , Riboldi Elena , Locati Massimo
Published: July 2010

The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote infiltration of leukocyte populations, among which tumor‐associated macrophages (TAM) represent a paradigm for cancer‐promoting inflammation. TAM orchestrate various aspects of cancer, including diversion and skewing of adaptive responses, cell growth, angiogenesis, matrix deposition and remodelling, the construction of a metastatic niche and actual metastasis, response to hormones and chemotherapeutic agents. Several lines of evidence indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, suggesting that during tumor progression macrophages undergo a phenotypic “switch”, eventually exhibiting the alternatively activated, “M2”, phenotype that is associated with immunosuppression, promotion of tumor angiogenesis and metastasis. Although recent studies have attempted to address the role of microenvironmental signals on TAM “reprogramming”, the interplay between innate and adaptive immunity is emerging as a crucial step of this event. In this issue of the European Journal of Immunology, a study demonstrates that B1 lymphocytes expressing IL‐10 play a key role in promoting a pro‐tumoral M2‐biased phenotype of macrophages. This article defines a new in vivo pathway of macrophage polarization and suggests that targeting B cells is a possible therapeutic intervention to reinstate anti‐cancer functions by TAM.
The Vibrational Spectra of the Cyanide Ligand Revisited: Double Bridging Cyanides
Authors: Kettle Sidney F. A. , Diana Eliano , Marchese Edoardo M. C. , Boccaleri Enrico , Croce Gianluca , Sheng Tianlu , Stanghellini Pier Luigi
Published: July 2010

The vibrational behaviour of complexes of general formula [(ML5CN)2M′L′4] with either a cis or trans geometry has been studied. The ν(CN) modes have been assigned on the basis of both infrared and Raman intensities. The CN vibrators are but weakly coupled, particularly so in the cis arrangement. The spectroscopic analysis offers insights into the interpretation of the spectra of Prussian Blue species as cis and trans M–CN–M′–NC–M complexes may be regarded as building blocks of Prussian Blue. The structure of the complex [(CO)5MoCNNi(Bipy)2NCMo(CO)5] confirms the expected cis geometry of the metal core. The complex [Cp(dppe)FeNCRu(4‐EtPy)4CNFeCp(dppe)]3+[PF6–]3 was prepared by oxidising the reduced form (2+ cation) and its crystal structure was determined and compared with that of the starting complex. Analysis of the structural and spectroscopic data led to the conclusion that the two iron atoms in the oxidised form have different charges and that the vibrations of the two CN groups are essentially independent. DFT calculations indicate that although π‐bonding and antibonding occur, electrostatic effects (as described by the IVSE model) are probably more important.
pH‐Responsive Switching of the Near‐Infrared Absorption of the Water‐Soluble Bis(o‐diiminobenzosemiquinonato)platinum(II) Complex
Authors: Masuya Atsuko , Iki Nobuhiko , Kabuto Chizuko , Ohba Yasunori , Yamauchi Seigo , Hoshino Hitoshi
Published: July 2010

The electronic structure of a water‐soluble near‐infrared (NIR)‐absorbing complex was determined to be singlet diradical [PtII(LISQ)2]2– [(LISQ)2–· = o‐diiminosulfobenzosemiquinonate radical] by X‐ray diffraction and 1H NMR spectroscopy. Cyclic voltammetry (CV) showed redox reactions of [PtII(LISQ)2]2– to give [PtII(LISQ)(LIBQ)]– (E${1 \over 2}$1 = –0.26 V vs. Fc+/Fc) and [PtII(LISQ)(LPDI)]3– (E${1 \over 2}$2 = –1.46 V) [(LIBQ)– = o‐diiminosulfobenzoquinonate, (LPDI)3– = o‐phenylenediiminesulfonate]. The monoradical structure of the latter was confirmed by electron paramagnetic resonance (EPR) spectroscopy. Splitting of the reduction wave of [PtII(LISQ)(LIBQ)]– in CV and the weak EPR signal suggested the formation of a dimer. Because the rest potential of the solution exceeds Epa1 at pH 4.0, the decrease in the NIR absorption at pH < 4.0 can be attributed to the oxidation of [PtII(LISQ)2]2– followed by dimerization.
Synthesis and Reaction Chemistry of Heterodi‐ and Heterotrimetallic Transition‐Metal Complexes Based on 1‐(Diphenylphosphanyl)‐1′‐terpyridylferrocene
Authors: Hildebrandt Alexander , Wetzold Nora , Ecorchard Petra , Walfort Bernhard , Rüffer Tobias , Lang Heinrich
Published: July 2010

The reaction of [Fe(η5‐C5H4PPh2)(η5‐C5H4terpy)] (5; terpy = 2,2′:6′,2″‐terpyridin‐4′‐yl) with diverse transition‐metal compounds including [PtCl2(Et2S)2], [Pd(cod)X2], [AuCl(tht)], [CuBr], [Mo(CO)4(nbd)], and [{RhCl(cod)}2] (X = Cl, Br; tht = tetrahydrothiophene; nbd = norbornadiene; cod = cyclooctadiene) to afford heterobi‐ and trimetallic complexes and a coordination polymer is reported. The following compounds were prepared: [Fe(η5‐C5H4PPh2{PtCl2(SEt2)})(η5‐C5H4terpy)] (7), trans‐[PtCl2{(Ph2P‐η5‐C5H4)(η5‐C5H4terpy)Fe}2] (9), [Fe(η5‐C5H4PPh2PdCl2)(η5‐C5H4terpy)] (12), [Fe{η5‐C5H4PPh2(Cl3Pd–)}(η5‐C5H4terpy{(dmso)2ClNi+})] (14), trans‐[PdX2{(Ph2P‐η5‐C5H4)(η5‐C5H4terpy)Fe}2] (16a, X = Cl;16b, X = Br), [Mo(CO)4{(η5‐C5H4PPh2)(η5‐C5H4terpy)Fe}2](17), [Fe{η5‐C5H4Ph2P(CuBr)}(η5‐C5H4terpy)]n (19), [Fe{η5‐C5H4Ph2P(AuCl)}(η5‐C5H4terpy)] (22), [Fe(η5‐C5H4Ph2P{Rh(cod)Cl})(η5‐C5H4terpy)] (23), [Ru({η5‐C5H4Ph2P(AuCl)}(η5‐C5H4terpy)Fe)2]Cl2 (25), and [Fe{η5‐C5H4PPh2(PdCl2)}{η5‐C5H4‐CH=CHC(O)(py)}] (26). The molecular structures of 5, 9, 12, 14, 16b, 22, and 26 in the solid state are reported. They show typical features of related phosphanylferrocenes and terpyridylferrocenes. Characteristic of 12 is a C–H activation as a result of the close distance of palladium to the terpyridyl moiety. Complexes 12, 26, and [PdCl2(dppf)] [dppf = 1,1′‐bis(diphenylphosphanyl)ferrocene], for comparison, were used in preliminary studies as catalysts in the carbon–carbon coupling of iodobenzene with tert‐butyl acrylate to give (E)‐tert‐butyl cinnamate. The conversion amounts to 80 % with a turnover number of 160 and turnover frequency of 48 h–1.
“Tail–Tail Dimerization” of Ferrocene Amino Acid Derivatives
Authors: Siebler Daniel , Förster Christoph , Heinze Katja
Published: July 2010

Acid anhydrides of N‐protected 1′‐aminoferrocene‐1‐carboxylic acid (Fca) have been prepared and spectroscopically characterized (protection group Boc, Fmoc, Ac; 4a–4c). The structure of the Boc‐derivative 4a has been determined by single‐crystal X‐ray crystallography. An intramolecular N–H···O hydrogen bond involving the carbamate units results in a ring structure containing the two ferrocene units, the anhydride moiety, and the hydrogen bond. In the crystal, the individual molecules are connected by intermolecular N–H···O hydrogen bonds of the carbamate unit. Experimental and theoretical studies suggest that the ring motif is also a dominant species in solution. Electronic communication across the anhydride moiety is found to be very weak as judged from electrochemical, spectroscopic, and theoretical experiments.