bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for Transitioning From PECS to SGD. Part 2: Maintaining Communication Competency
Authors: Frost Lori , McGowan Joy Silverman
Published: April 2012

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.
Self-Anchored Rating Scales: Creating Partnerships for Post-Aphasia Change
Authors: Fox Lynn E. , Andrews Mary A. , Andrews James
Published: April 2012

The self-anchored rating scale (SARS) is a technique used by systemic family counselors that has been applied to treating speech and language disorders, most recently aphasia. SARS aids the clinician in understanding the lived experience of the person with aphasia and members of his or her social support network. Skilled use of SARS helps people with aphasia and their families identify reasonable therapy goals and shows how their opinions and actions contribute to achieving those goals. In this article, we describe five steps in the SARS process, as well as specific counseling techniques that help the clinician involve the person with aphasia and his or her family in all aspects of the therapeutic process. Case study data illustrate outcomes for one family, showing improvement in behaviors identified as important by a client, the client's spouse, and their clinician.
Role of surface trap states on two-dimensional electron gas density in InAlN/AlN/GaN heterostructures
Authors: Pandey S. , Cavalcoli D. , Fraboni B. , Cavallini A. , Brazzini T. , Calle F.
Published: April 2012

In order to clarify the effect of charged dislocations and surface donor states on the transport mechanisms in polar AlInN/AlN/GaN heterostructures, we have studied the current-voltage characteristics of Schottky junctions fabricated on AlInN/AlN/GaN heterostructures. The reverse-bias leakage current behaviour has been interpreted with a Poole-Frenkel emission of electrons from trap states near the metal-semiconductor junction to dislocation induced states. The variation of the Schottky barrier height as a function of the AlN layer thickness has been measured and discussed, considering the role of the surface states in the formation of the two dimensional electron gas at AlN/GaN interface.
Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations
Authors: Brailsford John A. , Danishefsky Samuel J.
Published: April 2012

Nonglycosylated erythropoietin bearing acetamidomethyl protecting groups at the cysteine residues has been synthesized via chemical methods. Alanine ligation was used to assemble four peptide fragments, themselves prepared by solid phase peptide synthesis. This work outlines a route for the synthesis of homogeneous glycosylated erythropoietin.
Context-specific control and the Stroop negative priming effect
Authors: Milliken Bruce , Thomson David R. , Bleile Karmen , MacLellan Ellen , Giammarco Maria
Published: April 2012

The present study highlights the utility of context-specific learning for different probe types in accounting for the commonly observed dependence of negative priming on probe selection. Using a Stroop priming procedure, Experiments 1a and 1b offered a demonstration that Stroop priming effects can differ qualitatively for selection and no-selection probes when probe selection is manipulated between subjects, but not when it is manipulated randomly from trial to trial within subject (see also Moore, 1994). In Experiments 2 and 3, selection and no-selection probes served as two contexts that varied randomly from trial to trial, but for which proportion repeated was manipulated separately. A context-specific proportion repeated effect was observed in Experiment 2, characterized by modest quantitative shifts in the repetition effects as a function of the context-specific proportion repeated manipulation. However, with a longer intertrial interval in Experiment 3, a context-specific proportion repeated manipulation that focused on the no-selection probes changed the repetition effect qualitatively, from negative priming when the proportion repeated was .25 to positive priming when the proportion repeated was .75. The results are discussed with reference to the role of rapid, context-specific learning processes in the integration of prior experiences with current perception and action.
An initial search for visual overshadowing
Authors: Harris Kevin R. , Paul Stephen T. , Adams-Price Carolyn E.
Published: April 2012

A consistent, albeit fragile, finding over the last couple of decades has been that verbalization of hard-to-verbalize stimuli, such as faces, interferes with subsequent recognition of the described target stimulus. We sought to elicit a similar phenomenon whereby visualization interferes with verbal recognition—that is, visual overshadowing. We randomly assigned participants ( n = 180) to either concrete (easy to visualize) or abstract (difficult to visualize) sentence conditions. Following presentation, participants were asked to verbalize the sentence, visualize the sentence, or work on a filler task. As predicted, visualization of an abstract verbal stimulus resulted in significantly lower recognition accuracy; unexpectedly, however, so did verbalization. The findings are discussed within the framework of fuzzy-trace theory.
On the flexibility of letter position coding during lexical processing: Evidence from eye movements when reading Thai
Authors: Winskel Heather , Perea Manuel , Ratitamkul Theeraporn
Published: April 2012

Previous research supports the view that initial letter position has a privileged role in comparison to internal letters for visual-word recognition in Roman script. The current study examines whether this is the case for Thai. Thai is an alphabetic script in which ordering of the letters does not necessarily correspond to the ordering of a word's phonemes. Furthermore, Thai does not normally have interword spaces. We examined whether the position of transposed letters (internal, e.g., porblem, vs. initial, e.g., rpoblem) within a word influences how readily those words are processed when interword spacing and demarcation of word boundaries (using alternatingbold text) is manipulated. The eye movements of 54 participants were recorded while they were reading sentences silently. There was no apparent difference in degree of disruption caused when reading initial and internal transposed-letter nonwords. These findings give support to the view that letter position encoding in Thai is relatively flexible and that actual identity of the letter is more critical than letter position. This flexible encoding strategy is in line with the characteristics of Thai—that is, the flexibility in the ordering of the letters and the lack of interword spaces, which creates a certain level of ambiguity in relation to the demarcation of word boundaries. These findings point to script-specific effects operating in letter encoding in visual-word recognition and reading.
Palestinian youth and the Arab Spring. Learning to think critically: a case study
Authors: Naser-Najjab Nadia
Published: April 2012

The subject of this paper is a case study based on evidence gathered informally through delivery of a course at Birzeit University entitled ‘Modern and Contemporary European Civilization’ and from end-of-semester evaluations that asked students to reflect on the impact of the course on their lives. The author is, naturally, aware of the limitation of the methodology used in this study, and does not claim that its findings can be generalized authoritatively to a wider group of people in the Arab world. What is clear, however, if one considers reviews of internet blogs and media programme debates, is that extrapolations from this evidence have wider reference, revealing commonalities and similarities between Palestinians living in the Occupied Territories and Arab youth involved in the Arab Spring on the subject of political reform. The discussions engaged in by my students actually parallel the debates generated by traditionalists and secularists in post-revolution Egypt and Tunisia. These debates revolve around what it means to live in a civil, democratic state that grants social justice and freedoms, and crucially, at present led by scholars and politicians, address the possibility of reconciling the concept of modernity with Islam and the legislative framework of Islamic law (sharīʿah). It could be argued that the data collected are specific to this one case study, since Palestinians living under Israeli occupation form a unique group in the Arab world and probably are more concerned with basic issues of daily life and more sensitive to Western concepts of modernity. The significance of this data is, however, that gathered during the Arab Spring, they were based on reactions to material covered in a class which related to issues raised by the Arab revolutions, such as democracy, liberalism and revolution. Furthermore, these tentative findings suggest that more research is needed into issues such as the role of education, gender, tolerance and the reconciliation of Islam with modernity – areas of interest which are of particular importance at a time when Islamic groups are winning elections and debates on concepts of authority, democracy and liberalism occupy the foreground of media programmes in countries such as Egypt and Tunisia.
Adherence of heart failure patients to exercise: barriers and possible solutions
Authors: Conraads Viviane M. , Deaton Christi , Piotrowicz Ewa , Santaularia Nuria , Tierney Stephanie , Piepoli Massimo F. , Pieske Burkert , Schmid Jean‐Paul , Dickstein Kenneth , Ponikowski Piotr P. , Jaarsma Tiny
Published: April 2012

The practical management of heart failure remains a challenge. Not only are heart failure patients expected to adhere to a complicated pharmacological regimen, they are also asked to follow salt and fluid restriction, and to cope with various procedures and devices. Furthermore, physical training, whose benefits have been demonstrated, is highly recommended by the recent guidelines issued by the European Society of Cardiology, but it is still severely underutilized in this particular patient population. This position paper addresses the problem of non‐adherence, currently recognized as a main obstacle to a wide implementation of physical training. Since the management of chronic heart failure and, even more, of training programmes is a multidisciplinary effort, the current manuscript intends to reach cardiologists, nurses, physiotherapists, as well as psychologists working in the field.
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

Aim:

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.
Disentangling the relationship between sex-biased gene expression and X-linkage
Authors: Meisel Richard P. , Malone John H. , Clark Andrew G.
Published: April 2012

X chromosomes are preferentially transmitted through females, which may favor the accumulation of X-linked alleles/genes with female-beneficial effects. Numerous studies have shown that genes with sex-biased expression are under- or over-represented on the X chromosomes of a wide variety of organisms. The patterns, however, vary between different animal species, and the causes of these differences are unresolved. Additionally, genes with sex-biased expression tend to be narrowly expressed in a limited number of tissues, and narrowly expressed genes are also non-randomly X-linked in a taxon-specific manner. It is therefore unclear whether the unique gene content of the X chromosome is the result of selection on genes with sex-biased expression, narrowly expressed genes, or some combination of the two. To address this problem, we measured sex-biased expression in multipleDrosophilaspecies and at different developmental time points. These data were combined with available expression measurements fromDrosophila melanogasterand mouse to reconcile the inconsistencies in X-chromosome content among taxa. Our results suggest that most of the differences betweenDrosophilaand mammals are confounded by disparate data collection/analysis approaches as well as the correlation between sex bias and expression breadth. Both theDrosophilaand mouse X chromosomes harbor an excess of genes with female-biased expression after controlling for the confounding factors, suggesting that the asymmetrical transmission of the X chromosome favors the accumulation of female-beneficial mutations in X-linked genes. However, some taxon-specific patterns remain, and we provide evidence that these are in part a consequence of constraints imposed by the dosage compensation mechanism inDrosophila.
Evidence for reproductive philopatry in the bull shark Carcharhinus leucas
Authors: Tillett B. J. , Meekan M. G. , Field I. C. , Thorburn D. C. , Ovenden J. R.
Published: April 2012

Reproductive philopatry in bull sharks Carcharhinus leucas was investigated by comparing mitochondrial (NADH dehydrogenase subunit 4, 797 base pairs and control region genes 837 base pairs) and nuclear (three microsatellite loci) DNA of juveniles sampled from 13 river systems across northern Australia. High mitochondrial and low microsatellite genetic diversity among juveniles sampled from different rivers (mitochondrial φST = 0·0767, P < 0·05; microsatellite FST = −0·0022, P > 0·05) supported female reproductive philopatry. Genetic structure was not further influenced by geographic distance (P > 0·05) or long‐shore barriers to movement (P > 0·05). Additionally, results suggest that C. leucas in northern Australia has a long‐term effective population size of 11 000–13 000 females and has undergone population bottlenecks and expansions that coincide with the timing of the last ice‐ages.
The use and abuse of photographic identification in sharks and rays
Authors: Marshall A. D. , Pierce S. J.
Published: April 2012

The use of photography to discriminate between individuals in a population using natural markings or aberrations is increasingly being utilized to support field research on elasmobranchs. This non‐intrusive method has facilitated investigation of a wide variety of subjects including population composition, abundance estimates, residency and movement, demography and social behaviours. Here the first detailed review of photo‐identification as a research technique for sharks and rays is provided, and its assumptions, current applications and potential highlighted. The limitations and practical considerations of photographic studies are also investigated with recommendations on initial survey design and ongoing data collection using current technology. Future directions are also explored with an emphasis on a move towards standardized approaches and automated recognition programmes to facilitate global collaborative work.
Movement patterns of the draughtboard shark Cephaloscyllium laticeps (Scyliorhinidae) determined by passive tracking and conventional tagging
Authors: Awruch C. A. , Frusher S. D. , Stevens J. D. , Barnett A.
Published: April 2012

A combination of passive tracking and conventional tagging was used to provide insight into the movement patterns of the draughtboard shark Cephaloscyllium laticeps, the most common catshark in coastal areas of southern Australia. A series of acoustic receivers deployed throughout south‐eastern Tasmania as well as a receiver array along an isolated reef, Crayfish Point Reserve (CPR), passively tracked 25 C. laticeps from January to July 2003. Cephaloscyllium laticeps were present from 4 to 98 days. The majority of the C. laticeps stayed within the CPR where most individuals were active throughout the night. They were found actively moving (i.e. when a C. laticeps was consecutively detected by two or more non‐overlapping receivers, suggesting the individual was moving) and spending periods of minor movements (i.e. when an individual was consecutively detected by only one receiver, suggesting it was at rest). The length of these minor movements periods, observed both day and night, ranged from 1 h to 5 days. In addition to passive tracking, 1552 conventionally tagged C. laticeps were released in the eastern and south‐western coastal areas of Tasmania and within the CPR between January 2000 and April 2007. The CPR showed a higher recapture rate, 38%, than eastern and south‐western areas where the recapture rates were 10 and 3%, respectively. Within the CPR, 36% of the sharks were recaptured on multiple occasions. The maximum time at liberty ranged from 1 month to 7 years. The majority of the C. laticeps were recaptured in the vicinity of where they were released (<10 km), although larger longer‐term movements of up to 300 km were recorded. The large amount of multiple recaptures within the CPR, in addition to acoustic tagging results, indicated a high degree of site fidelity for C. laticeps. This isolated reef appears to be an important habitat for this species, and therefore, the current protection status of this area is probably beneficial for the conservation of C. laticeps.
A review of the biology, fisheries and conservation of the whale shark Rhincodon typus
Authors: Rowat D. , Brooks K. S.
Published: April 2012

Although the whale shark Rhincodon typus is the largest extant fish, it was not described until 1828 and by 1986 there were only 320 records of this species. Since then, growth in tourism and marine recreation globally has lead to a significant increase in the number of sightings and several areas with annual occurrences have been identified, spurring a surge of research on the species. Simultaneously, there was a great expansion in targeted R. typus fisheries to supply the Asian restaurant trade, as well as a largely un‐quantified by‐catch of the species in purse‐seine tuna fisheries. Currently R. typus is listed by the IUCN as vulnerable, due mainly to the effects of targeted fishing in two areas. Photo‐identification has shown that R. typus form seasonal size and sex segregated feeding aggregations and that a large proportion of fish in these aggregations are philopatric in the broadest sense, tending to return to, or remain near, a particular site. Somewhat conversely, satellite tracking studies have shown that fish from these aggregations can migrate at ocean‐basin scales and genetic studies have, to date, found little graphic differentiation globally. Conservation approaches are now informed by observational and environmental studies that have provided insight into the feeding habits of the species and its preferred habitats. Notwithstanding these advances, there remain notable gaps in the knowledge of this species particularly with respect to the life history of neonates and adults who are not found in the feeding aggregations.
Biological vulnerability of two exploited sharks of the genus Deania (Centrophoridae)
Authors: Irvine S. B. , Daley R. K. , Graham K. J. , Stevens J. D.
Published: April 2012

Life‐history parameters of Deania calcea and Deania quadrispinosa suggested that their productivity was very low. Maturity (LT50) occurs at c. 80% of maximum observed total lengths (LT) for both species and sexes. A large proportion of mature females were neither pre‐ovulatory nor pregnant, and the reproductive cycle included a distinct resting phase after pregnancy. For D. calcea, mean ovarian fecundity was 12 and maximum observed litter size was 10 (average of six); D. quadrispinosa averaged 17 pups per litter. Birth LT was 28–33 cm for D. calcea and 23–25 cm for D. quadrispinosa. The male and female reproductive cycles were aseasonal, and consequently, the length of the reproductive cycle could not be determined. Preliminary ageing data from dorsal‐spine growth bands suggested that female D. calcea lived to 31–36 years and males to 24–32 years. The LT‐at‐age data using external bands on the spines showed maturity occurring at 15·5 years (males) and 21·5 years (females), whereas banding on the internal dentine indicated maturity at 10·5 and 17·5 years for males and females. Thus, a female lifetime of 31–36 years allowed for a maximum of 7 litters if a 2 year cycle is assumed or only five litters with a 3 year cycle, resulting in a lifetime fecundity of only 42 pups (2 year cycle) or even lower (3 year cycle).
The contrasting role of heterochromatin in the differentiation of sex chromosomes: an overview from Neotropical fishes
Authors: Cioffi M. B. , Moreira‐Filho O. , Almeida‐Toledo L. F. , Bertollo L. A. C.
Published: April 2012

During the evolutionary process of the sex chromosomes, a general principle that arises is that cessation or a partial restriction of recombination between the sex chromosome pair is necessary. Data from phylogenetically distinct organisms reveal that this phenomenon is frequently associated with the accumulation of heterochromatin in the sex chromosomes. Fish species emerge as excellent models to study this phenomenon because they have much younger sex chromosomes compared to higher vertebrates and many other organisms making it possible to follow their steps of differentiation. In several Neotropical fish species, the heterochromatinization, accompanied by amplification of tandem repeats, represents an important step in the morphological differentiation of simple sex chromosome systems, especially in the ZZ/ZW sex systems. In contrast, multiple sex chromosome systems have no additional increase of heterochromatin in the chromosomes. Thus, the initial stage of differentiation of the multiple sex chromosome systems seems to be associated with proper chromosomal rearrangements, whereas the simple sex chromosome systems have an accumulation of heterochromatin. In this review, attention has been drawn to this contrasting role of heterochromatin in the differentiation of simple and multiple sex chromosomes of Neotropical fishes, highlighting their surprising evolutionary dynamism.
Does proximity to aquatic pollution affect reproductive traits in a wild‐caught intertidal fish?
Authors: Sopinka N. M. , Fitzpatrick J. L. , Taves J. E. , Ikonomou M. G. , Marsh‐Rollo S. E. , Balshine S.
Published: April 2012

How chronic exposure to aquatic pollution affects reproductive traits was assessed in nesting wild‐caught plainfin midshipman Porichthys notatus in areas with low and high contaminant exposure on Vancouver Island, British Columbia. Males in high‐exposure areas had a greater degree of testicular asymmetry, sperm with shorter heads and fewer live eggs in their nests. The results of this study provide important insights into the potential consequences of contaminant exposure on the reproductive physiology of wild‐caught fishes.
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

LIGHT [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.
Hepatitis C virus and the brain
Authors: Fletcher N. F. , McKeating J. A.
Published: April 2012

Summary.  Hepatitis C virus (HCV) is an enveloped, positive‐strand RNA virus of the family Flaviviridae that primarily infects hepatocytes, causing acute and chronic liver disease. HCV is also associated with a variety of extrahepatic symptoms including central nervous system (CNS) abnormalities, cognitive dysfunction, fatigue and depression. These symptoms do not correlate with the severity of liver disease and are independent of hepatic encephalopathy. HCV RNA has been associated with CNS tissue, and reports of viral sequence diversity between brain and liver tissue suggest independent viral evolution in the CNS and liver. This review will explore the data supporting HCV infection of the CNS and how this fits into our current understanding of HCV pathogenesis.
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, 157–165

Nuclear carrier and RNA‐binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes

Aims: 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

Striatal 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.
Production of cloned pigs expressing human thrombomodulin in endothelial cells
Authors: Yazaki Satoko , Iwamoto Masaki , Onishi Akira , Miwa Yuko , Hashimoto Michiko , Oishi Takatsugu , Suzuki Shunichi , Fuchimoto Dai‐ichiro , Sembon Shoichiro , Furusawa Tadashi , Liu DaGe , Nagasaka Takaharu , Kuzuya Takafumi , Ogawa Haruko , Yamamoto Koji , Iwasaki Kenta , Haneda Masataka , Maruyama Shoichi , Kobayashi Takaaki
Published: April 2012

Yazaki S, Iwamoto M, Onishi A, Miwa Y, Hashimoto M, Oishi T, Suzuki S, Fuchimoto D‐I, Sembon S, Furusawa T, Liu DG, Nagasaka T, Kuzuya T, Ogawa H, Yamamoto K, Iwasaki K, Haneda M, Maruyama S, Kobayashi T. Production of cloned pigs expressing human thrombomodulin in endothelial cells. Xenotransplantation 2012; 19: 82–91. © 2012 John Wiley & Sons A/S.

Abstract:  For long‐term xenograft survival, coagulation control is one of the remaining critical issues. Our attention has been directed toward human thrombomodulin (hTM), because it is expected to exhibit the following beneficial effects on coagulation control and cytoprotection: (i) to solve the problem of molecular incompatibility in protein C activation; (ii) to exert a role as a physiological regulator, only when thrombin is formed; (iii) to suppress direct prothrombinase activity; and (iv) to have anti‐inflammatory properties. hTM gene was transfected into pig (Landrace/Yorkshire) fibroblasts using pCAGGS expression vector and pPGK‐puro vector. After puromycin selection, only fibroblasts expressing a high level of hTM were collected by cell sorting and then applied to nuclear transfer. Following electroactivation and subsequent culture, a total of 1547 cleaved embryos were transferred to seven surrogate mother pigs. Two healthy cloned piglets expressing hTM were born, successfully grew to maturity and produced normal progeny. Immunohistochemical staining of organs from F1 generation pigs demonstrated hTM expression in endothelial cells as well as parenchymal cells. High expression was observed particularly in endothelial cells of kidney and liver. Aortic endothelial cells from cloned pigs were found to express hTM levels similar to human umbilical vein endothelial cells (HUVEC) and to make it possible to convert protein C into activated protein C. The blockade of human endothelial cell protein C receptor (hEPCR) significantly reduced APC production in HUVEC, but not in hTM‐PAEC. Although no bleeding tendency was observed in hTM‐cloned pigs, activated partial thromboplastin time (APTT) was slightly prolonged and soluble hTM was detected in pig plasma. hTM was expressed in platelets and mononuclear cells, but not in RBC. Cloned pigs expressing hTM in endothelial cells at a comparable level to HUVEC were produced. As complete suppression of antigen‐antibody reaction in the graft is essential for accurate assessment of transgene related to coagulation control, production of genetically engineered pigs expressing hTM and complement regulatory protein based on galactosyltransferase knockout is desired.
Xenotransplantation literature update, January–February 2012
Authors: Schneider Mårten K. J. , Seebach Jörg D.
Published: April 2012

Schneider MKJ, Seebach JD. Xenotransplantation literature update, January–February 2012. Xenotransplantation 2012; 19: 133–136 © 2012 John Wiley & Sons A/S.
What is the role of the (1→3)‐β‐d‐glucan assay in the screening of patients undergoing autologous haematopoietic stem‐cell transplantation?
Authors: Metan Gökhan , Koç A. N. , Kaynar Leyla G. , Atalay Altay , Öztürk Ahmet , Eser Bülent , Çetin Mustafa
Published: April 2012

The aim of this study is to determine the clinical contribution of (1→3)‐β‐d‐glucan (BDG) screening in the case of patients undergoing autologous haematopoietic stem‐cell transplantation (HSCT). The records at our stem‐cell transplantation centre were reviewed to identify the patients who underwent autologous HSCT between April 2009 and December 2010. Patients were classified as having proven invasive aspergillosis (IA), probable IA, or possible IA on the basis of the criteria established by the European Organization for Research and Treatment of Cancer and Mycoses Study Group (independent of the BDG results). During the study period, the patients were screened for BDG twice a week from transplant (day 0) until engraftment. Three patients were diagnosed with probable IA and five were diagnosed with possible IA. A total of 354 serum samples from79 patients who met the study inclusion criteria were used for statistical analysis. At the cut‐off value of 80 pg ml−1, the sensitivity was 27.2% [95% confidence interval (CI); 7.3–60.6]; specificity, 94.4% (95% CI; 91.3–96.5); positive predictive value, 6.2%; and negative predictive, 93.7%. The clinical contribution of the BDG assay as a screening test was relatively limited in this cohort of patients undergoing autologous HSCT.
Inflammatory bowel disease in Asia: A systematic review
Authors: Prideaux Lani , Kamm Michael A , De Cruz Peter P , Chan Francis K L , Ng Siew C
Published: April 2012

The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra‐intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.