bluuebunny/crossref_metadata_2025_split huggingface dataset:
Na+/H+ exchanger 1 inhibition contributes to K562 leukaemic cell differentiation
Authors: Jin Weina , Li Qinghua , Wang Jian , Chang Guoqiang , Lin Yani , Li Huawen , Wang Lihong , Gao Wei , Pang Tianxiang 
Published: April 2012

AbstractThe effect of hypoxia on the differentiation of chronic myeloid leukaemic K562 cells were studied, as was the role of the NHE1 (Na+/H+ exchanger 1). Hypoxia induced differentiation of K562 cells as seen by modifications in their morphological features, up‐regulation of C/EBPα (CCAAT/enhancer‐binding protein α), and marked IL‐8 (interleukin‐8) release. Inhibition of NHE1 under hypoxia additionally enhanced the level of C/EBPα and further promoted leukaemic cells differentiation. Pharmacological inhibition of p38 MAPK (mitogen‐activated protein kinase) also significantly suppressed C/EBPα expression under hypoxia conditions after NHE1 inhibition. These results indicate the enhancement of hypoxia‐induced K562 differentiation by NHE1 inhibition, which may be due to up‐regulation of C/EBPα via p38 MAPK signalling pathway, which suggests a possible therapeutic target of NHE1 under hypoxia microenvironment in the treatment of leukaemic diseases.
New AAC Access Strategy for Gesture Tracking: A Technical Note
Authors: Fager Susan , Jakobs Tom , Beukelman David , Ternus Tricia , Schley Haylee 
Published: April 2012

Abstract
This article summarizes the design and evaluation of a new augmentative and alternative communication (AAC) interface strategy for people with complex communication needs and severe physical limitations. This strategy combines typing, gesture recognition, and word prediction to input text into AAC software using touchscreen or head movement tracking access methods. Eight individuals with movement limitations due to spinal cord injury, amyotrophic lateral sclerosis, polio, and Guillain Barre syndrome participated in the evaluation of the prototype technology using a head-tracking device. Fourteen typical individuals participated in the evaluation of the prototype using a touchscreen.
What Are the Attention Demands of Aided AAC?
Authors: Thistle Jennifer J. , Wilkinson Krista M. 
Published: April 2012

Abstract
The act of communicating requires the management and use of attention. Communicating using aided Augmentative and Alternative Communication (AAC) may place unique attentional demands because of the length of time it can take to convey a message. From turning on the AAC device to activating the voice output, there are multiple tasks that call upon attention. Reducing the length of time to communicate may reduce the amount of attention required. Using the existing literature base related to display design, we offer considerations for designing the visual display that influence the speed of aided AAC.
Identifying, Locating, and Sequencing Visual-Graphic Symbols: A Perspective on the Role of Visuospatial and Temporal Memory
Authors: Wagner Barry T. , Shaffer Lauren A. , Swim Olivia A. 
Published: April 2012

Abstract
It is well documented in the augmentative and alternative communication (AAC) literature that many children exhibit difficulty identifying visual-graphic symbols on aided communication displays during the communication process. Researchers have identified a number of variables that influence children's abilities to identify these symbols. Some of these variables include the type of symbol used, language organization, display type, and the actual physical dimensions of symbols such as size and color. One important variable that has not been considered or evaluated in AAC display designs is children's developmental visuospatial and temporal memory abilities. In this article, we will discuss the role that developing visuospatial and temporal memory may play in the identification, location, and sequence of visual-graphic symbols. We will review basic terminology regarding memory function related to object-location memory and present clinical considerations for easing the memory and attentional processing demands of selecting visual-graphic symbols.
Strategies for Transitioning From PECS to SGD. Part 2: Maintaining Communication Competency
Authors: Frost Lori , McGowan Joy Silverman 
Published: April 2012

Abstract
The Picture Exchange Communication System (PECS) is an evidence-based AAC system that often is chosen as a first intervention for young children with complex communication needs who are not developing spoken communication. Speech language pathologists (SLPs) often plan to transition to a speech-generating device (SGD) for long-term use after students successfully progress through the PECS protocol. The minimum criterion for device selection and purchase should be appropriate and independent use of the SGD across environments. The transition process should begin with an assessment of the student's PECS skills so modifications can be made to facilitate the transition to the SGD. Teaching strategies that are part of the PECS protocol are used to teach spontaneous, efficient, and effective use of the SGD. Successful transition occurs when the student uses the SGD in social interactions similar to his use of PECS and when he or she has developed the skills that will ensure continued language growth.
Local Anesthetic-like Inhibition of Voltage-gated Na+Channels by the Partial μ-opioid Receptor Agonist Buprenorphine
Authors: Leffler Andreas , Frank Georg , Kistner Katrin , Niedermirtl Florian , Koppert Wolfgang , Reeh Peter W. , Nau Carla 
Published: April 2012

Background
Opioids induce analgesia mainly by inhibiting synaptic transmission via G protein-coupled opioid receptors. In addition to analgesia, buprenorphine induces a pronounced antihyperalgesia and is an effective adjuvant to local anesthetics. These properties only partially apply to other opioids, and thus targets other than opioid receptors are likely to be employed. Here we asked if buprenorphine inhibits voltage-gated Na(+) channels.

Methods
Na(+) currents were examined by whole cell patch clamp recordings on different recombinant Na(+) channel α-subunits. The effect of buprenorphine on unmyelinated mouse C-fibers was examined with the skin-nerve preparation. Data are presented as mean ± SEM.

Results
Buprenorphine induced a concentration-dependent tonic (IC(50) 33 ± 2 μM) and use-dependent block of endogenous Na(+) channels in ND7/23 cells. This block was state-dependent and displayed slow on and off characteristics. The effect of buprenorphine was reduced on local anesthetic insensitive Nav1.4-mutant constructs and was more pronounced on the inactivation-deficient Nav1.4-WCW mutant. Neuronal (Nav1.3, Nav1.7, and Nav1.8), cardiac (Nav1.5), and skeletal muscle (Nav1.4) α-subunits displayed small differences in tonic block, but similar degrees of use-dependent block. According to our patch clamp data, buprenorphine blocked electrically evoked action potentials in C-fiber nerve terminals. Buprenorphine was more potent than other opioids, including morphine (IC(50) 378 ± 20 μM), fentanyl (IC(50) 95 ± 5 μM), sufentanil (IC(50) 111 ± 6 μM), remifenatil (IC(50) 612 ± 17 μM), and tramadol (IC(50) 194 ± 9 μM).

Conclusions
Buprenorphine is a potent local anesthetic and blocks voltage-gated Na(+) channels via the local anesthetic binding site. This property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia.
Indications, Methodology, and Interpretation of Combined Esophageal Impedance‐pH Monitoring in Children
Authors: Wenzl Tobias G. , Benninga Marc A. , Loots Clara M. , Salvatore Silvia , Vandenplas Yvan ,   ESPGHAN EURO‐PIG Working Group
Published: April 2012

ABSTRACTAim:The aim of the study was to provide an updated position statement from the ESPGHAN European Pediatric Impedance Working Group on different technical aspects such as indications, methodology, and interpretation of multichannel intraluminal impedance‐pH monitoring (MII‐pH).Methods:Evidence was used where available, but the article is based mainly on expert opinion and consensus.Results:MII‐pH provides more information than simple pH monitoring because reflux detection is not limited to acid reflux. Different companies provide commercialized MII‐pH recording systems, making the method widely available and useable in daily clinical practice; however, the technique still has limitations: high cost, limited additional value regarding therapeutic implications, and lack of evidence‐based parameters for the assessment of gastroesophageal reflux and symptom association in children.Conclusions:MII‐pH recording is a promising procedure needing further validation and development to increase its additional benefit over conventional investigation techniques. The added value of the technique regards mainly clinical circumstances in which nonacid or weakly acid reflux may be relevant such as persisting symptoms during antireflux treatment with proton pump inhibitors and feeding‐related reflux; and assessing specific discontinuous symptoms thought to be associated with gastroesophageal reflux; and research.
Increased plasma LIGHT levels in patients with atopic dermatitis
Authors: Kotani H , Masuda K , Tamagawa-Mineoka R , Nomiyama T , Soga F , Nin M , Asai J , Kishimoto S , Katoh N 
Published: April 2012

SummaryLIGHT [the name of which is derived from ‘homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes’], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1β in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.
Nuclear carrier and RNA‐binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes
Authors: Davidson Y. S. , Robinson A. C. , Hu Q. , Mishra M. , Baborie A. , Jaros E. , Perry R. H. , Cairns N. J. , Richardson A. , Gerhard A. , Neary D. , Snowden J. S. , Bigio E. H. , Mann D. M. A. 
Published: April 2012

Y. S. Davidson, A. C. Robinson, Q. Hu, M. Mishra, A. Baborie, E. Jaros, R. H. Perry, N. J. Cairns, A. Richardson, A. Gerhard, D. Neary, J. S. Snowden, E. H. Bigio and D. M. A. Mann (2013) Neuropathology and Applied Neurobiology39, 157–165Nuclear carrier and RNA‐binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changesAims: We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA‐binding protein‐associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD‐FUS). Methods: Eight cases of FTLD‐FUS (five cases of atypical FTLD‐U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP‐43 inclusions served as reference cases. Results: The inclusion bodies in FTLD‐FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP‐43 aggregations in FTLD. Conclusions: Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP‐43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements.
Effects of cocaine self‐administration and extinction on D2‐like and A2A receptor recognition and D2‐like/Gi protein coupling in rat striatum
Authors: Frankowska Malgorzata , Marcellino Daniel , Adamczyk Przemyslaw , Filip Malgorzata , Fuxe Kjell 
Published: April 2012

ABSTRACTStriatal adenosine (A)2‐dopamine (D)2 receptor (R) heteromers exist with antagonistic interactions. We have studied these Rs and their interactions during cocaine self‐administration and extinction using a ‘yoked’ protocol to understand the role of motivational mechanisms behind the adaptive observed. In the ventral striatum, a significant increase in the A2AR density was observed in rats that received ‘yoked’ cocaine during maintenance phase and following its extinction while this significant increase was only observed after extinction from cocaine self‐administration. In the dorsal striatum, a significant increase in the affinity of A2ARs was determined in the two groups of rats that received cocaine during maintenance. D2‐like Rs were significantly increased in the dorsal striatum of animals that received ‘yoked’ cocaine during maintenance. In the rat dorsal, but not the ventral, striatum significant reductions in the EC50 values for dopamine and increases in the guanosine5′‐([γ]‐thio)triphosphate (GTPγS) accumulation were observed following active and passive cocaine injections during maintenance. After 10‐day extinction, a significant reduction of the Bmax value of GTPγS accumulation was demonstrated in the dorsal striatum of rats previously self‐administered cocaine, while a significant reduction of the EC50 value for dopamine in the ventral striatum was found in the ‘yoked’ cocaine group. By comparing the cocaine self‐administration group with the ‘yoked’ cocaine group, evidence for the existence of motivational mechanisms that guide adaptive changes in the A2AR and D2R and in the D2‐Gi coupling differentially developed in the ventral and dorsal striatum during cocaine maintenance and its extinction has been demonstrated.
Long‐term effects of PERV‐specific RNA interference in transgenic pigs
Authors: Semaan Marwan , Kaulitz Danny , Petersen Björn , Niemann Heiner , Denner Joachim 
Published: April 2012

Semaan M, Kaulitz D, Petersen B, Niemann H, Denner J. Long‐term effects of PERV‐specific RNA interference in transgenic pigs. Xenotransplantation 2012; 19: 112–121. © 2012 John Wiley & Sons A/S.Abstract: Background:  Porcine endogenous retroviruses (PERVs) represent a risk of xenotransplantation using porcine cells, tissues, or organs, as they are integrated in the porcine genome and have been shown to be able to infect human cells in vitro. To increase viral safety by RNA interference, transgenic pigs expressing a PERV‐specific small hairpin (sh)RNA targeted to a highly conserved sequence in the pol gene (pol2) were generated in which expression of PERVs was reduced (Xenotransplantation, 15, 2008, 38). However, it remains to be shown how long expression of the shRNA and the RNA interference is effective in reducing PERV expression.Methods:  To analyze the long‐term duration of RNA interference, expression of the PERV‐specific pol2 shRNA and inhibition of PERV expression was studied repeatedly in fibroblasts and peripheral blood mononuclear cells (PBMCs) of transgenic pigs over a period of 3 yr, when animals were sacrificed and expression was studied in different organs. Expression of the PERV‐specific shRNA was measured using a newly developed real‐time PCR, and expression of PERV was measured using a PERV‐specific real‐time PCR.Results:  Over a period of 3 yr, PERV‐specific shRNA and green fluorescent protein (GFP) as reporter of the vector system were consistently expressed in transgenic animals. PERV expression was significantly reduced during the entire period. Levels of PERV and shRNA expression were different in the various organs. PERV expression was highest in the spleen and the lungs and lowest in liver and heart. However, in all organs of the transgenic pigs, PERV expression was inhibited compared with the vector control animals.Conclusions:  Transgenic pigs expressing PERV‐specific shRNA maintained their specific RNA interference long term, suggesting that PERV expression in the xenotransplants will be suppressed over extended periods of time.
Evaluation of a novel reconstituted bone xenograft using processed bovine cancellous bone in combination with purified bovine bone morphogenetic protein
Authors: Long Bi , Dan Li , Jian Liu , Yunyu Hu , Shu He , Zhi Yuan 
Published: April 2012

Long B, Dan L, Jian L, Yunyu H, Shu H, Zhi Y. Evaluation of a novel reconstituted bone xenograft using processed bovine cancellous bone in combination with purified bovine bone morphogenetic protein. Xenotransplantation 2012; 19: 122–132. © 2012 John Wiley & Sons A/S.Abstract: Background:  Xenogeneic grafting represents an alternative to autogenous grafting in osseous reconstruction and exhibits many beneficial properties. However, the usefulness of xenogeneic bone relies on necessary processing procedures for removing antigens and viruses, and preserving biological activities simultaneously. By chemical treatment of bovine cancellous bone to make it an antigen‐free scaffold, and extraction of bone morphogenetic protein (BMP) from bovine cortical bone, followed by recombination of the scaffold with the BMP, we developed a new grafting material, reconstituted bone xenograft (RBX).Methods:  In this study, scanning electron microscope and energy dispersive X‐ray were first employed to observe the structure and components of RBX. Then the biomechanical property was evaluated by applying compression in a materials testing machine. Subsequently, the immunologic evaluation was performed by measuring galactose‐alpha‐1,3‐galactose (α‐gal) epitope in vivo and proinflammatory cytokine (TNF‐α) secreted by human monocytic cell line (THP‐1) in vitro. Finally, this RBX was implanted into segmental radial defects in a rabbit model, and its ability to treat large bone defects was specifically evaluated.Results:  Although the compressive strength of RBX was 10% lower than that of unprocessed bovine cancellous bone (UBCB), the basic porous structure and natural components were still kept in this composite. The α‐gal xenoantigen level was significantly lower in RBX (P < 0.05) compared with UBCB. Moreover, the TNF‐α level was significantly (P < 0.05) reduced compared with UBCB when THP‐1 was exposed to RBX. On the other hand, RBX appeared to induce cartilage formation from immature cell populations and resulted in osteogenesis through endochondral‐like ossification from 4 to 12 weeks in repairing segmental bone defects.Conclusions:  These results demonstrate that RBX, with its natural microstructure and components, certain mechanical strength and strong osteoinductivity without evoking immune rejection, has significant potential for the treatment of bone defects.
Identification of human preformed antibody targets in GTKO pigs
Authors: Burlak Christopher , Wang Zheng‐Yu , Chihara Ray K. , Lutz Andrew J. , Wang Yueren , Estrada Jose L. , Tector A. Joseph 
Published: April 2012

Burlak C, Wang ZY, Chihara RK, Lutz AJ, Wang Y, Estrada JL, Tector AJ. Identification of human preformed antibody targets in GTKO pigs. Xenotransplantation 2012; 19: 92–101. © 2012 John Wiley & Sons A/S.Abstract: Background:  Human preformed antibodies continue to recognize porcine xenografts, despite the advent of α‐galactosyltransferase knockout (GTKO) pigs. This study examined the potential reactivity of human preformed IgG and IgM antibodies toward antigens in the GTKO pig liver.Methods:  Human serum was analyzed for the concentration of IgG, IgM, anti‐αgal antibody, anti‐non‐αgal antibody and cytotoxicity toward domestic and GTKO fibroblasts and liver sinusoidal endothelial cells (LSEC). We detected preformed antibodies in human serum directed toward GTKO pig liver cells and tissue samples using advanced proteomic techniques. The targets of preformed antibodies were identified by MALDI TOF TOF mass spectrometry and validated by confocal microscopy, immunoblot, and immunoprecipitation.Results:  Human serum used in this study contained 2.06 μg/ml IgG and 0.013 μg/ml IgM directed toward GTKO fibroblasts. Human IgG and IgM bound to GTKO LSEC in a dose‐dependent manner and were cytotoxic. We detected 357 protein spots recognized by human IgG and 233 by human IgM. Two hundred and nineteen proteins were common to both human IgG and IgM. Mass spectrometry identified numerous immunoreactive proteins, of which 19 were membrane proteins on liver cells. The most significant to this study were α‐enolase, CFTR, and E‐cadherin, which were abundant in GTKO pig tissues and expressed on the surface of GTKO LSEC. Human IgG captured α‐enolase, CFTR, and E‐cadherin by immunoprecipitation validating the proteomic identification.Conclusion:  These experiments indicate that several membrane antigens in GTKO pigs could be recognized directly by human IgG or IgM. Further studies on the contribution of these antigens to antibody‐mediated xenograft rejection are necessary.