bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot‐Marie‐Tooth type 4A disease
Authors: Pedrola Laia , Espert Antonio , Valdés‐Sánchez Teresa , Sánchez‐Piris Maribel , Sirkowski Erich E. , Scherer Steven S. , Fariñas Isabel , Palau Francesc 
Published: April 2008

AbstractMutations in the mitochondrial protein GDAP1 are the cause of Charcot‐Marie‐Tooth type 4A disease (CMT4A), a severe form of peripheral neuropathy associated with either demyelinating, axonal or intermediate pheno‐types. GDAP1 is located in the outer mitochondrial membrane and it seems that may be related with the mitochondrial network dynamics. We are interested to define cell expression in the nervous system and the effect of mutations in mitochondrial morphology and pathogenesis of the disease. We investigated GDAP1 expression in the nervous system and dorsal root ganglia (DRG) neuron cultures. GDAP1 is expressed in motor and sensory neurons of the spinal cord and other large neurons such as cerebellar Purkinje neurons, hippocampal pyramidal neurons, mitral neurons of the olfactory bulb and cortical pyramidal neurons. The lack of GDAP1 staining in the white matter and nerve roots suggested that glial cells do not express GDAP1. In DRG cultures satellite cells and Schwann cells were GDAP1‐negative. Overexpression of GDAP1‐induced fragmentation of mitochondria suggesting a role of GDAP1 in the fission pathway of the mitochondrial dynamics. Missense mutations showed two different patterns: most of them induced mitochondrial fragmentation but the T157P mutation showed an aggregation pattern. Whereas null mutations of GDAP1 should be associated with loss of function of the protein, missense mutations may act through different pathogenic mechanisms including a dominant‐negative effect, suggesting that different molecular mechanisms may underlay the pathogenesis of CMT4A.
Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction
Authors: Liehn E. A. , Merx M. W. , Postea O. , Becher S. , Djalali‐Talab Y. , Shagdarsuren E. , Kelm M. , Zernecke A. , Weber C. 
Published: April 2008

AbstractMyocardial necrosis triggers inflammatory changes and a complex cytokine cascade that are only incompletely understood. The chemokine receptor CCR1 mediates inflammatory recruitment in response to several ligands released by activated platelets and up‐regulated after myocardial infarction (MI). Here, we assess the effect of CCR1 on remodelling after MI using Ccr1‐deficient (Ccr1−/−) mice. MI was induced in Ccr1−/− or wild‐type mice by proximal ligation of the left anterior descending (LAD). Mice were sacrificed and analysed at day 1, 4, 7, 14 and 21 after MI. While initial infarct areas and areas at risk did not differ between groups, infarct size increased to 20.6±8.4% of the left ventricle (LV) in wild‐type mice by day 21 but remained at 11.2±1.2% of LV (P<0.05) in Ccr1−/− mice. This attenuation in infarct expansion was associated with preserved LV function, as analysed by isolated heart studies according to Langendorff. Left ventricular developed pressure was 84.5±19.8 mmHg in Ccr1−/− mice compared to 49.0±19.7 mmHg in wild‐type mice (P<0.01) and coronary flow reserve was improved in Ccr1−/− mice. An altered post‐infarct inflammatory pattern was observed in Ccr1−/− mice characterized by diminished neutrophil infiltration, accelerated monocyte/lymphocyte infiltration, decreased apoptosis, increased cell proliferation and earlier myofibroblast population in the infarcted tissue. In conclusion, functional impairment and structural remodelling after MI is reduced in the genetic absence of Ccr1 due to an abrogated early inflammatory recruitment of neutrophils and improved tissue healing, thus revealing a potential therapeutic target.
Cancer stem cells: implications for the progression and treatment of metastatic disease
Authors: Croker A.K , Allan A.L 
Published: April 2008

Introduction
The metastatic process
The cancer stem cell hypothesis
Parallels between stem cell behaviour and metastatic behaviour
Therapeutic implications
Conclusions and future directions

AbstractMetastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re‐initiate tumour growth to form life‐threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess “stem‐like” characteristics. Classical properties of normal stem cells are strikingly reminiscent of the observed experimental and clinical behaviour of metastatic cancer cells, including an unlimited capacity for self renewal; the requirement for a specific ‘niche’or microenvironment to grow; use of the stromal cell‐derived factor 1 (SDF‐1)/chemokine receptor 4 (CXCR4) axis for migration; enhanced resistance to apoptosis and an increased capacity for drug resistance. Therefore, in addition to playing a role in primary tumour formation, we believe that CSCs are also key players in the metastatic process. We will review the current evidence supporting this idea and discuss the potential implications of the CSC hypothesis with regards to experimental investigation and treatment of metastatic disease.
Acetylcholinesterase‐R increases germ cell apoptosis but enhances sperm motility
Authors: Mor I. , Sklan E.H. , Podoly E. , Pick M. , Kirschner M. , Yogev L. , Bar‐Sheshet Itach S. , Schreiber L. , Geyer B. , Mor T. , Grisaru D. , Soreq H. 
Published: April 2008

AbstractChanges in protein subdomains through alternative splicing often modify protein‐protein interactions, altering biological processes. A relevant example is that of the stress‐induced up‐regulation of the acetylcholinesterase (AChE‐R) splice variant, a common response in various tissues. In germ cells of male transgenic TgR mice, AChE‐R excess associates with reduced sperm differentiation and sperm counts. To explore the mechanism(s) by which AChE‐R up‐regulation affects spermatogenesis, we identified AChE‐R's protein partners through a yeast two‐hybrid screen. In meiotic spermatocytes from TgR mice, we detected AChE‐R interaction with the scaffold protein RACK1 and elevated apoptosis. This correlated with reduced scavenging by RACK1 of the pro‐apoptotic TAp73, an outcome compatible with the increased apoptosis. In contrast, at later stages in sperm development, AChE‐R's interaction with the glycolytic enzyme enolase‐α elevates enolase activity. In transfected cells, enforced AChE‐R excess increased glucose uptake and adenosine tri‐phosphate (ATP) levels. Correspondingly, TgR sperm cells display elevated ATP levels, mitochondrial hyperactivity and increased motility. In human donors' sperm, we found direct association of sperm motility with AChE‐R expression. Interchanging interactions with RACK1 and enolase‐α may hence enable AChE‐R to affect both sperm differentiation and function by participating in independent cellular pathways.
The alternative complement pathway revisited
Authors: Harboe Morten , Mollnes Tom Eirik 
Published: April 2008

Introduction
Methods to study and modify the alternative pathway
Influence of AP amplification on the effect of specific activation of the other initial pathways
Properdin
Influence of AP in deficiency states
Complement in sepsis
Concluding remarks
AbstractAlternative pathway amplification plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways, but the quantitative role of the amplification is insufficiently investigated. In experimental models of human diseases in which a direct activation of alternative pathway has been assumed, this interpretation needs revision placing a greater role on alternative amplification. We recently documented that the alternative amplification contributed to 80–90% of C5 activation when the initial activation was highly specific for the classical pathway. The recent identification of properdin as a recognition factor directly initiating alternative pathway activation, like C1q in the classical and mannose‐binding lectin in the lectin pathway, initiates a renewed interest in the reaction mechanisms of complement. Complement and Toll‐like receptors, including the CD14 molecule, are two main upstream recognition systems of innate immunity, contributing to the inflammatory reaction in a number of conditions including ischaemia‐reperfusion injury and sepsis. These systems act as ‘double‐edged swords’, being protective against microbial invasion, but harmful to the host when activated improperly or uncontrolled. Combined inhibition of complement and Toll‐like receptors/CD14 should be explored as a treatment regimen to reduce the overwhelming damaging inflammatory response during sepsis. The alternative pathway should be particularly considered in this regard, due to its uncontrolled amplification in sepsis. The alternative pathway should be regarded as a dual system, namely a recognition pathway principally similar to the classical and lectin pathways, and an amplification mechanism, well known, but quantitatively probably more important than generally recognized.
Nogo‐A and Nogo‐66 receptor in amyotrophic lateral sclerosis
Authors: Teng Felicia Yu Hsuan , Tang Bor Luen 
Published: April 2008

AbstractNogo/reticulon (RTN)‐4 has been strongly implicated as a disease marker for the motor neuron disease amyotrophic lateral sclerosis (ALS). Nogo isoforms, including Nogo‐A, are ectopically expressed in the skeletal muscle of ALS mouse models and patients and their levels correlate with the disease severity. The notion of a direct involvement of Nogo‐A in ALS aetiology is supported by the findings that Nogo‐A deletion in mice reduces muscle denervation and prolongs survival, whereas overexpression of Nogo‐A destabilizes motor nerve terminals and promotes denervation. Another intriguing, and somewhat paradoxical, recent finding revealed that binding of the Nogo‐66 receptor (NgR) by either agonistic or antagonistic Nogo‐66‐derived peptides protects against p75 neurotrophin receptor (p75NTR)‐dependent motor neuron death. Ligand binding by NgR could result in subsequent engagement of p75NTR, and this association could preclude pro‐apoptotic signalling by the latter. Understanding the intricate interplay among Nogo isoforms, NgR and p75NTR in ALS disease progression may provide important, therapeutically exploitable information.
Progressive recovery of osseoperception as a function of the combination of implant‐supported prostheses
Authors: Batista Mauro , Bonachela Wellington , Soares Janir 
Published: April 2008

AbstractThe extraction of teeth involves the elimination of extremely sensitive periodontal mechanoreceptors, which play an important role in oral sensory perception.Objectives: The aim of this study was to evaluate the recovery of interocclusal sensory perception for micro‐thickness in individuals with different types of implant‐supported prostheses.Materials and Methods: Wearers of complete dentures (CDs) comprised the negative control group (group A, n=17). The experimental group consisted of wearers of prostheses supported by osseointegrated implants (Group B, n=29), which was subsequently divided into 4 subgroups: B1 (n=5) – implant supported overdentures (ISO) occluding with CD; B2 (n=6) – implant‐supported fixed prostheses (ISFP) occluding with CD; B3 (n=8) – wearers of maxillary and mandibular ISFP, and B4 (n=10) – ISFP occluding with natural dentition (ND). Individuals with ND represented the positive control group (Group C, n=24). Aluminum foils measuring 10 μm, 24 μm, 30 μm, 50 μm, 80 μm, and 104 μm thickness were placed within the premolar area, adding up to 120 tests for each individual.Results: The mean tactile thresholds of groups A, B1, B2, B3, B4, and C were 92 μm, 27 μm, 27 μm, 14 μm, 10 μm, and 10 μm, respectively. [Correction added after publication online 18 April 2008: in the preceding sentence 92 μm, 27 μm, 14 μm, 10 μm and 10 μm, was corrected to 92 μm, 27 μm, 27 μm, 14 μm, 10 μm and 10 μm.] The Kruskal‐Wallis test revealed significant difference among groups (P<0.05). The Dunn test revealed that group A was statistically different from groups C, B3, and B4, and that B1 and B2 were statistically different from group C.Conclusion: Progressive recovery of osseoperception as a function of the combination of implant‐supported prostheses could be observed. Moreover, ISO and/or ISFP combinations may similarly maximize the recovery of osseoperception.
Spacing and crowding among African and Caucasian children
Authors: Mugonzibwa EA , Eskeli R , Laine‐Alava MT , Kuijpers‐Jagtman AM , Katsaros C 
Published: April 2008

Structured AbstractAuthors –  Mugonzibwa EA, Eskeli R, Laine‐Alava MT, Kuijpers‐Jagtman AM, Katsaros CObjective –  To determine spacing and crowding according to ethnic group, gender and dental emergence stage among Tanzanian African and Caucasian children.Design –  Cross‐sectional epidemiological clinical study.Setting –  A total of 869 African (428 boys, 441 girls) and 706 Caucasian (319 boys, 387 girls) school children, aged 3½–16 years.Main Outcome Measures –  Comparison of spacing and crowding between African and Caucasian children according to gender and dental emergence stage.Results –  Spacing was more often found in the maxilla, while crowding was more common in the mandible. Only during the transition of the maxillary permanent front teeth was there significantly more spacing in Caucasians. No gender differences were found. In both samples spacing decreased during later emergence stages. Crowding was more often found in Caucasian children than in African children. In Caucasian children the frequency of crowding increased with advanced emergence stages, while for Africans the trend was not consistent.Conclusion –  When planning resources for orthodontic treatment for different populations as well as planning treatment for individuals, ethnic background and emergence stage of the dentition need to be considered.
The Story of Abraham and Models of Human Identity
Authors: Mills Mary 
Published: April 2008

AbstractThis paper explores the profiles of the women characters Sarah and Hagar as models of human identity. The two characters can only be explored through reading the over-arching narrative of the story of Abraham. Their profiles and narrated personalities have to be extracted from that narrative, but there is a two-sided nature of this necessity. If Sarah and Hagar cannot be separated from the biblical narrator's engagement with father Abraham, neither can Abraham function as father of the nations except through his interaction with these two women. The reader is thus led towards an understanding of how the stories of Genesis 12–24 deal with the issue of parenthood.The body of the paper consists in a close reading of the biblical material following a method of reading which is rooted in the use of imagination as an exegetical tool – a style adopted by Paul in his allegorical approach to Sarah and Hagar in Galatians 4. This approach opens into narrative criticism with a focus on characterisation and on the interactions of Sarah, Hagar and Abraham, caught up in a Domestic Comedy. The women's characters are explored through the themes of parenthood as other, the other woman and woman as other. A final section explores some of the points of narrative ethics to be extracted from the close textual readings of the paper, with reference to the writings of Paul Ricoeur and Emmanuel Levinas. It is suggested that female as well as male characters may offer fruitful models for human identity.
Islam and Diversity: Alternative Voices within Contemporary Islam
Authors: Calderini Simonetta 
Published: April 2008

AbstractIslam contains a greater plurality of theology than is often realised. Here two “alternative voices” are chosen as examples of how cultural accretions can be questioned to what is taken to be the original, pure voice of Islam. Amina Wadud has led a mixed congregation in prayer in New York and has demonstrated, not without opposition, that women can be imams. There follows a discussion of the historical debate about women as imams and reactions to Wadud's actions. The second voice is Hasan Askari, an Indian Muslim who has written widely on inter-faith dialogue. He maintains that to reduce differences between Judaism, Christianity and Islam, differences should be interpreted symbolically rather than literally. He questions all claims to finality in any religion and he believes that historical Islam has yet to be transformed to “universal Islam”. Religious differences can only be finally transcended at a level of mystical experience.
The Shakespeare Authorship Debate Revisited
Authors: Smith Emma 
Published: April 2008

AbstractWho wrote Shakespeare? And does it matter? Since Delia Bacon's researches in the mid‐nineteenth century, writers have questioned whether Shakespeare of Stratford really did write the works attributed to him, and proposed numerous alternative authors including Francis Bacon, the Earl of Oxford and Christopher Marlowe. This article does not endorse this scepticism, but instead treats the sceptical phenomenon as a wayward contribution to Shakespearean studies, discussing the history and methodology of these anti‐Stratfordian claims, to assess their hold on generations of interested amateurs including Henry James, Nathaniel Hawthorne and Sigmund Freud. The authorship debate is conceptualised according to different paradigms: as a conspiracy theory, as a reaction against the growing professionalisation of literary studies within universities, and as a version of the child's wish for more glamorous parents, theorised by Freud in ‘Family Romances’. Its ideological force – both socially conservative – a nobleman must have written the plays – and hermeneutically radical – their messages are potentially dangerous so require the utmost secrecy – is discussed. Finally I relate the authorship debate to recent critical analyses of Shakespearean collaborations with other authors, and suggest that this is the direction in which its probing energies might most usefully be taken in future.
Innovations in Aged Care: The aged care pain chart: An innovative approach to assessing, managing and documenting pain in older people
Authors: Edvardsson David , Katz Benny , Nay Rhonda 
Published: April 2008

This article presents the development and initial testing of a comprehensive pain chart for the assessment, management and documentation of pain in older people in subacute and residential aged care. The pain chart was developed from existing assessment scales and pain indicators, and is targeting needs of older people in residential care and geriatric hospital settings with high prevalence of cognitive impairments. The chart is based on self‐report of pain but allows for observation of pain‐related behaviours for those unable to report pain. The chart consists of one evaluative and one documentation dimension, and was evaluated by a group of clinicians in geriatric hospital care (n = 15) and residential aged care (n = 6). The chart was found to be content valid, informative and easy to use, facilitating clinical assessments and monitoring, and assisting visual readings of patients’ temporal pain trends.
Midodrine Improves Orgasm in Spinal Cord-Injured Men: The Effects of Autonomic Stimulation
Authors: Soler Jean Marc , Previnaire Jean Gabriel , Plante Pierre , Denys Pierre , Chartier-Kastler Emmanuel 
Published: April 2008

ABSTRACT

Introduction
Orgasm is less frequent in men with spinal cord injury (SCI) than in able-bodied subjects, and is poorly understood.

Aim
To assess the effect of autonomic stimulation on orgasm in SCI men using midodrine, an alpha1-adrenergic agonist agent.

Materials and Methods
Penile vibratory stimulation (PVS) was performed in 158 SCI men on midodrine as part of a treatment for anejaculation, after they failed a baseline PVS. A maximum of four trials were performed, weekly, with increasing doses of midodrine.

Main Outcome Measure
The presence and type of ejaculation, orgasm experiences, and cardiovascular data were collected.

Results
Ejaculation either antegrade or retrograde was obtained in 102 SCI men (65%). Orgasm without ejaculation was reported by 14 patients (9%) on baseline PVS. Ninety-three patients (59%) experienced orgasm during PVS on midodrine. Orgasm was significantly related to the presence of ejaculation in 86 patients (84%), and more strikingly to antegrade ejaculation (pure or mixed with retrograde), i.e., in 98% of 70 patients. Orgasm was significantly more frequent in patients with upper motor neuron and incomplete lesions who present somatic responses during PVS. There was no effect of the presence of psychogenic erection. There was a significant increase in both systolic and diastolic blood pressure. Sixteen patients, mainly tetraplegics, developed intense autonomic dysreflexia (AD) that required an oral nicardipine chlorhydrate.

Conclusion
Orgasm is the brain's cognitive interpretation of genital sensations and somatic responses, AD, and ejaculation. Intact sacral and T10-L2 cord segments are mandatory, allowing coordination between internal and external sphincters. Autonomic stimulation with midodrine enhances orgasm rate, mainly by creating antegrade ejaculation.
Profibrotic Role of Myostatin in Peyronie's Disease
Authors: Cantini Liliana P. , Ferrini Monica G. , Vernet Dolores , Magee Thomas R. , Qian Ansha , Gelfand Robert A. , Rajfer Jacob , Gonzalez-Cadavid Nestor F. 
Published: April 2008

ABSTRACT

Introduction
The primary histologic finding in many urologic disorders, including Peyronie's disease (PD), is fibrosis, mainly mediated by the transforming growth factor β1 (TGFβ1).

Aim
To determine whether another member of the TGFβ family, myostatin, (i) is expressed in the human PD plaque and normal tunica albuginea (TA), their cell cultures, and the TGFβ1-induced PD lesion in the rat model; (ii) is responsible for myofibroblast generation, collagen deposition, and plaque formation; and (iii) mediates the profibrotic effects of TGFβ1 in PD.

Methods
Human TA and PD tissue sections, and cell cultures from both tissues incubated with myostatin and TGFβ1 were subjected to immunocytochemistry for myostatin and α-smooth muscle actin (ASMA). The cells were assayed by western blot, Real time-Polymerase chain reaction (RT-PCR), and ribonuclease protection. Myostatin cDNA and shRNA were injected, with or without TGFβ1, in the rat penile TA, and plaque size was estimated by Masson.

Main Outcome Measures
Myostatin expression in the human TA, the PD plaque, and their cell cultures, and myostatin effects on the PD-like plaque in the rat.

Results
A threefold overexpression of myostatin was found in the PD plaque as compared with the TA. In PD cells, myostatin expression was mainly in the myofibroblasts, and in the TA cells, it increased upon passage paralleling myofibroblast differentiation and was up-regulated by TGFβ1. Myostatin or its cDNA construct increased the myofibroblast number and collagen in TA cells. Myostatin was detected in the TGFβ1-induced PD-like plaque of the rat partly in the myofibroblasts, and in the TA. Myostatin cDNA injected in the TA induced a plaque and intensified the TGFβ1 lesion, which was not reduced by myostatin shRNA.

Conclusions
Myostatin is overexpressed in the PD plaque, partly because of myofibroblast generation. Although myostatin induces a plaque in the rat TA, it does not appear to mediate the one triggered by TGFβ1, thus suggesting that both proteins act concurrently and that therapy should target their common downstream effectors.