bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal Streptococcus anginosus‐associated pneumonia in a captive Sumatran orangutan (Pongo abelii)
Authors: Ihms E.A. , Daniels J.B. , Koivisto C.S. , Barrie M.T. , Russell D.S. 
Published: October 2013

AbstractBackgroundBacterial infections commonly affect the lungs and air sacs of orangutans; culture and identification is rarely performed and may have clinical relevance.MethodsNecropsy, histopathology and bacterial culture were performend on a captive adult male Sumatran orangutan with chronic air sacculitis. Bacterial speciation was confirmed by sequencing of the 16s–23s ribosomal DNA spacer region.ResultsNecropsy revealed severe suppurative pneumonia. Moderate growth of Streptoccocus anginosus was recovered from the lungs.ConclusionsThis is the first report of S. anginosus as a cause of fatal suppurative pneumonia in a non‐human primate.
Celastrol prevents cadmium‐induced neuronal cell death via targeting JNK and PTEN‐Akt/mTOR network
Authors: Chen Sujuan , Gu Chenjian , Xu Chong , Zhang Jinfei , Xu Yijiao , Ren Qian , Guo Min , Huang Shile , Chen Long 
Published: October 2013

AbstractCadmium (Cd), a toxic environmental contaminant, induces neurodegenerative diseases. Celastrol, a plant‐derived triterpene, has shown neuroprotective effects in various disease models. However, little is known regarding the effect of celastrol on Cd‐induced neurotoxicity. Here, we show that celastrol protected against Cd‐induced apoptotic cell death in neuronal cells. This is supported by the findings that celastrol strikingly attenuated Cd‐induced viability reduction, morphological change, nuclear fragmentation, and condensation, as well as activation of caspase‐3 in neuronal cells. Concurrently, celastrol remarkably blocked Cd‐induced phosphorylation of c‐Jun N‐terminal kinase (JNK), but not extracellular signal‐regulated kinases 1/2 and p38, in neuronal cells. Inhibition of JNK by SP600125 or over‐expression of dominant negative c‐Jun potentiated celastrol protection against Cd‐induced cell death. Furthermore, pre‐treatment with celastrol prevented Cd down‐regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and activation of phosphoinositide 3′‐kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling in neuronal cells. Over‐expression of wild‐type PTEN enhanced celastrol inhibition of Cd‐activated Akt/mTOR signaling and cell death in neuronal cells. The findings indicate that celastrol prevents Cd‐induced neuronal cell death via targeting JNK and PTEN‐Akt/mTOR network. Our results strongly suggest that celastrol may be exploited for the prevention of Cd‐induced neurodegenerative disorders.
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Celastrol, a plant‐derived triterpene, has shown neuroprotective effects. However, little is known regarding the effect of celastrol on cadmium (Cd) neurotoxicity. This study underscores that celastrol prevents Cd‐induced neuronal apoptosis via inhibiting activation of JNK (c‐Jun N‐terminal kinase) and Akt/mTOR network. Celastrol suppresses Cd‐activated Akt/mTOR pathway by elevating PTEN (phosphatase and tensin homolog). The findings suggest that celastrol may be exploited for the prevention of Cd‐induced neurodegenerative disorders.
Murine dopaminergic Müller cells restore motor function in a model of Parkinson's disease
Authors: Stutz Bernardo , da Conceição Fabio Silva Lima , Santos Luís Eduardo , Cadilhe Daniel Veloso , Fleming Renata L. , Acquarone Mariana , Gardino Patrícia F. , de Melo Reis Ricardo A. , Dickson Phillip W. , Dunkley Peter R. , Rehen Stevens , Houzel Jean‐Christophe , de Mello Fernando G. 
Published: October 2013

AbstractMüller cells constitute the main glial cell type in the retina where it interacts with virtually all cells displaying relevant functions to retinal physiology. Under appropriate stimuli, Müller cells may undergo dedifferentiation, being able to generate other neural cell types. Here, we show that purified mouse Müller cells in culture express a group of proteins related to the dopaminergic phenotype, including the nuclear receptor‐related 1 protein, required for dopaminergic differentiation, as well the enzyme tyrosine hydroxylase. These dopaminergic components are active, since Müller cells are able to synthesize and release dopamine to the extracellular medium. Moreover, Müller‐derived tyrosine hydroxylase can be regulated, increasing its activity because of phosphorylation of serine residues in response to agents that increase intracellular cAMP levels. These observations were extended to glial cells obtained from adult monkey retinas with essentially the same results. To address the potential use of dopaminergic Müller cells as a source of dopamine in cell therapy procedures, we used a mouse model of Parkinson's disease, in which mouse Müller cells with the dopaminergic phenotype were transplanted into the striatum of hemi‐parkinsonian mice generated by unilateral injection of 6‐hydroxydopamine. These cells fully decreased the apomorphine‐induced rotational behavior and restored motor functions in these animals, as measured by the rotarod and the forelimb‐use asymmetry (cylinder) tests. The data indicate local restoration of dopaminergic signaling in hemi‐parkinsonian mice confirmed by measurement of striatal dopamine after Müller cell grafting.
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Müller cells are the main glial cells in the retina. When these cells are cultured in the absence of neurons, they spontaneously express proteins of the dopaminergic phenotype, including the enzymes tyrosine hydroxylase (TH), L‐DOPA‐decarboxylase (DDC) and the dopamine transport system (DAT). In this study, we show this phenomenon is observed with Müller cells obtained from different species, including primates, and address the therapeutic potential of these cells, using a mouse model of Parkinson's disease (PD). ‘Dopaminergic Müller cells’ synthesize dopamine and release most of this neurotransmitter to the extracellular space, constituting a natural dopaminergic ‘pump’. When transplanted to the striatum of PD mice, Müller cells decreased their apomorphine‐induced rotational behavior and restored their overall motor functions, measured by rotarod and forelimb use asymmetry tests. Local restoration of dopaminergic signaling was also observed in grafted PD mice, by measuring striatum dopamine and its metabolite (DOPAC) levels (SB: 20µm).
KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase Mζ
Authors: Vogt‐Eisele Angela , Krüger Carola , Duning Kerstin , Weber Daniela , Spoelgen Robert , Pitzer Claudia , Plaas Christian , Eisenhardt Gisela , Meyer Annette , Vogt Gerhard , Krieger Markus , Handwerker Eva , Wennmann Dirk Oliver , Weide Thomas , Skryabin Boris V. , Klugmann Matthias , Pavenstädt Hermann , Huentelmann Matthew J. , Kremerskothen Joachim , Schneider Armin 
Published: October 2013

AbstractThe WWC1 gene has been genetically associated with human episodic memory performance, and its product KIdney/BRAin protein (KIBRA) has been shown to interact with the atypical protein kinase protein kinase M ζ (PKMζ). Although recently challenged, PKMζ remains a candidate postsynaptic regulator of memory maintenance. Here, we show that PKMζ is subject to rapid proteasomal degradation and that KIBRA is both necessary and sufficient to counteract this process, thus stabilizing the kinase and maintaining its function for a prolonged time. We define the binding sequence on KIBRA, a short amino acid motif near the C‐terminus. Both hippocampal knock‐down of KIBRA in rats and KIBRA knock‐out in mice result in decreased learning and memory performance in spatial memory tasks supporting the notion that KIBRA is a player in episodic memory. Interestingly, decreased memory performance is accompanied by decreased PKMζ protein levels. We speculate that the stabilization of synaptic PKMζ protein levels by KIBRA may be one mechanism by which KIBRA acts in memory maintenance.
imageKIBRA/WWC1 has been genetically associated with human episodic memory. KIBRA has been shown to be post‐synaptically localized, but its function remained obscure. Here, we show that KIBRA shields PKMζ, a kinase previously linked to memory maintenance, from proteasomal degradation via direct interaction. KIBRA levels in the rodent hippocampus correlate closely both to spatial memory performance in rodents and to PKMζ levels. Our findings support a role for KIBRA in memory, and unveil a novel function for this protein.
Non‐motor parkinsonian pathology in aging A53T α‐Synuclein mice is associated with progressive synucleinopathy and altered enzymatic function
Authors: Farrell Kaitlin F. , Krishnamachari Sesha , Villanueva Ernesto , Lou Haiyan , Alerte Tshianda N. M. , Peet Eloise , Drolet Robert E. , Perez Ruth G. 
Published: October 2013

AbstractAging, the main risk factor for Parkinson's disease (PD), is associated with increased α–synuclein levels in substantia nigra pars compacta (SNc). Excess α‐synuclein spurs Lewy‐like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate‐limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α–synuclein for behavior and α–synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α‐synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α‐synuclein. Low adrenal PP2A activity co‐occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α–synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α‐synuclein pathology associated with pre‐motor stages of PD.imageAging A53T α‐synuclein mice develop behaviors common to premotor Parkinson's disease (PD) with synucleinopathy occuring in adrenal gland, olfactory bulb, and intestine. Insoluble aggregated A53T α‐synuclein loses PP2A‐stimulatory‐effects, which normally down regulate dopamine synthesis. This is the first study to link adrenal synucleinopathy to catecholamine dysregulation and anxiety. The mice are an excellent model for testing emerging neuroprotective therapies for PD.
Lentivirus‐Mediated α‐Melanocyte‐Stimulating Hormone Overexpression in the Hypothalamus Decreases Diet Induced Obesity in Mice
Authors: Eerola K. , Nordlund W. , Virtanen S. , Dickens A. M. , Mattila M. , Ruohonen S. T. , Chua S. C. , Wardlaw S. L. , Savontaus M. , Savontaus E. 
Published: October 2013

Melanocyte stimulating hormone (MSH) derived from the pro‐hormone pro‐opiomelanocortin (POMC) has potent effects on metabolism and feeding that lead to reduced body weight in the long‐term. To determine the individual roles of POMC derived peptides and their sites of action, we created a method for the delivery of single MSH peptides using lentiviral vectors and studied the long‐term anti‐obesity effects of hypothalamic α‐MSH overexpression in mice. An α‐MSH lentivirus (LVi‐α‐MSH‐EGFP) vector carrying the N‘‐terminal part of POMC and the α‐MSH sequence was generated and shown to produce bioactive peptide in an in vitro melanin synthesis assay. Stereotaxis was used to deliver the LVi‐α‐MSH‐EGFP or control LVi‐EGFP vector to the arcuate nucleus (ARC) of the hypothalamus of male C57Bl/6N mice fed on a high‐fat diet. The effects of 6‐week‐treatment on body weight, food intake, glucose tolerance and organ weights were determined. Additionally, a 14‐day pairfeeding study was conducted to assess whether the weight decreasing effect of the LVi‐α‐MSH‐EGFP treatment is dependent on decreased food intake. The 6‐week LVi‐α‐MSH‐EGFP treatment reduced weight gain (8.4 ± 0.4 g versus 12.3 ± 0.6 g; P < 0.05), which was statistically significant starting from 1 week after the injections. The weight of mesenteric fat was decreased and glucose tolerance was improved compared to LVi‐EGFP treated mice. Food intake was decreased during the first week in the LVi‐α‐MSH‐EGFP treated mice but subsequently increased to the level of LVi‐EGFP treated mice. The LVi‐EGFP injected control mice gained more weight even when pairfed to the level of food intake by LVi‐α‐MSH‐EGFP treated mice. We demonstrate that gene transfer of α‐MSH, a single peptide product of POMC, into the ARC of the hypothalamus, reduces obesity and improves glucose tolerance, and that factors other than decreased food intake also influence the weight decreasing effects of α‐MSH overexpression in the ARC. Furthermore, viral MSH vectors delivered stereotaxically provide a novel tool for further exploration of chronic site‐specific effects of POMC peptides.
Building an open academic environment – a new approach to empowering students in their learning of anatomy through ‘Shadow Modules’
Authors: Scott Jonathan L. , Moxham Bernard J. , Rutherford Stephen M. 
Published: October 2013

AbstractTeaching and learning in anatomy is undertaken by a variety of methodologies, yet all of these pedagogies benefit from students discussing and reflecting upon their learning activities. An approach of particular potency is peer‐mediated learning, through either peer‐teaching or collaborative peer‐learning. Collaborative, peer‐mediated, learning activities help promote deep learning approaches and foster communities of practice in learning. Students generally flourish in collaborative learning settings but there are limitations to the benefits of collaborative learning undertaken solely within the confines of modular curricula. We describe the development of peer‐mediated learning through student‐focused and student‐led study groups we have termed ‘Shadow Modules’. The ‘Shadow Module’ takes place parallel to the formal academically taught module and facilitates collaboration between students to support their learning for that module. In ‘Shadow Module’ activities, students collaborate towards curating existing online open resources as well as developing learning resources of their own to support their study. Through the use of communication technologies and Web 2.0 tools these resources are able to be shared with their peers, thus enhancing the learning experience of all students following the module. The Shadow Module activities have the potential to lead to participants feeling a greater sense of engagement with the subject material, as well as improving their study and group‐working skills and developing digital literacy. The outputs from Shadow Module collaborative work are open‐source and may be utilised by subsequent student cohorts, thus building up a repository of learning resources designed by and for students. Shadow Module activities would benefit all pedagogies in the study of anatomy, and support students moving from being passive consumers to active participants in learning.
Origin of the unique morphology of the shoulder girdle in turtles
Authors: Nagashima Hiroshi , Hirasawa Tatsuya , Sugahara Fumiaki , Takechi Masaki , Usuda Ryo , Sato Noboru , Kuratani Shigeru 
Published: October 2013

AbstractThe shoulder girdle of turtles has a triradiate morphology. Although its dorsal process represents the scapular blade, the skeletal identities of the two ventral processes remain uncertain. To elucidate the question, developmental patterns of the girdles were compared between Chinese soft‐shelled turtles, chickens, and mice. Despite the morphological diversity of adults, the initial primordia of the shoulder girdles showed similar morphological patterns. The ventral two processes developed from the anlagen comparable to those of the acromion and the coracoid in other amniotes. The developmental pattern of the acromion is very similar among embryos, whereas that of the coracoid in mammals differs from that in non‐mammals, implying that coracoids are not homologous between non‐mammals and mammals. Therefore, amniotes have retained the ancestral pattern of the girdle anlage, and the shoulder girdle of turtles has been achieved through a transformation of the pattern in the late ontogenic period.
The complex ontogenetic trajectory of mandibular shape in a laboratory mouse
Authors: Swiderski Donald L. , Zelditch Miriam L. 
Published: October 2013

AbstractThe mouse mandible is a popular model system that continues to be the focus of studies in evo‐devo and other fields. Yet, little attention has been given to the role of postnatal growth in producing the adult form. Using cleared and stained specimens, we describe the timing of tooth and jaw development and changes in jaw size and shape from postnatal day 1 (p1) through weaning to adulthood. We found that tooth development is relatively advanced at birth, and that the functional adult dentition is in place by p15 (just before the start of weaning). Shape analysis showed that the trajectory of mandible shape changes direction at least twice between birth and adulthood, at p7 and p15. At each stage there are changes in shape to all tooth‐ and muscle‐bearing regions and, at each change of direction, all of these regions change their pattern of growth. The timing of the changes in direction in Mus suggests there are signals that redirect growth patterns independently of changes in function and loading associated with weaning and jaw muscle growth. A better understanding of these signals and how they produce a functionally integrated mandible may help explain the mechanisms guiding evolutionary trends and patterns of plasticity and may also provide valuable clues to therapeutic manipulation of growth to alleviate the consequences of trauma or disease.
Gender differences in sagittal standing alignment before pubertal peak growth: the importance of subclassification and implications for spinopelvic loading
Authors: Dolphens Mieke , Cagnie Barbara , Vleeming Andry , Vanderstraeten Guy , Danneels Lieven 
Published: October 2013

AbstractThe aim of this study was to analyze gender differences in sagittal standing alignment at pre‐peak height velocity age thereby applying a scientifically sound and practically oriented classification scheme for overall standing balance. The study population consisted of healthy boys (n = 639) and girls (n = 557) before pubertal peak growth. During subjects' habitual standing, sagittal plane measures of the spine, pelvis and lower limbs were collected using a clinical screening protocol. With each subject classified as one of three postural types (neutral, sway‐back, or leaning‐forward), differences in sagittal plane alignment were analyzed between sexes. The results revealed clear differences between genders in each of the postural types. Within the neutral and sway‐back postural subgroups, boys presented more forward inclination of the trunk, more thoracic kyphosis and more pelvis backtilt compared with girls. Within the leaning‐forward category, girls displayed more forward trunk lean, less thoracic kyphosis and more pelvic anteversion. A state of lumbar segmental hyperextension appeared to exist in female leaning‐forward subjects. Our results reveal for the first time that sagittal standing alignment is different between prepubescent boys and girls when subjects are appropriately subclassified, and conversely represent a ‘wash‐out effect’ when pooled. When the classification system is applied, gender‐specificity in gravity line position is suggested, implying gender‐related differences in lever arms and thus load. Present findings may add to our understanding of gender‐specific biomechanical challenges posed by habitual posture, and may shed new light on sagittal standing alignment as a possible contributory factor in developmental spinal‐pelvic disorders.
A belief in the soul may contribute to the stress experienced in the dissecting room
Authors: Martyn Helen , Barrett Anthony , Nicholson Helen D. 
Published: October 2013

AbstractThe aim of this research was to explore whether medical students believe in a soul and how this may affect their dissecting experience. Three questionnaires were delivered electronically to the 2011 cohort of second‐year medical students over a 2‐year period. At the University of Otago, students enter medicine via three categories: Health Sciences First Year (following 1 year of university); postgraduate (following a Bachelors or higher degree); and ‘other’ category entry (Allied Health Professional or 3 years after a Bachelors degree). The entry category, age, ethnicity and gender of the students were collected; 51.6% of the students believed in the concept of a soul. On a scale of 1–5, students ranked the importance of religion/spirituality as 2.69. Those who believed in a soul were more likely to have a religious/spiritual component to their life and be males or ‘other’ category entrants. However, there were many students who believed in the soul who did not have a religious/spiritual association, suggesting that this belief extends beyond religion. Those who believed in a soul had significantly higher anticipatory stress and experienced higher levels of stress during dissection. A higher proportion of students in the ‘other’ category entrants believed in the concept of the soul and also had significantly higher levels of stress during dissection. Our data suggest that a belief in a soul may affect students' experiences in dissecting. Incorporating the teaching of humanities with anatomy may help medical students as they assimilate both the biomedical and philosophical aspects of dissection.
Safety incidents involving confused and forgetful older patients in a specialised care setting – analysis of the safety incidents reported to the HaiPro reporting system
Authors: Kinnunen‐Luovi Kaisa , Saarnio Reetta , Isola Arja 
Published: October 2013

Aims and objectivesTo describe the safety incidents involving confused and forgetful older patients in a specialised care setting entered in the HaiPro reporting system.BackgroundAbout 10% of patients experience a safety incident during hospitalisation, which causes or could cause them harm. The possibility of a safety incident during hospitalisation increases significantly with age. A mild or moderate memory disorder and acute confusion are often present in the safety incidents originating with an older patient.DesignThe design of the study was action research with this study using findings from one of the first‐phase studies, which included qualitative and quantitative analysed data.MethodsData were collected from the reporting system for safety incidents (HaiPro) in a university hospital in Finland. There were 672 reported safety incidents from four acute medical wards during the years 2009–2011, which were scrutinised. Seventy‐five of them were linked to a confused patient and were analysed.ResultsThe majority of the safety incidents analysed involved patient‐related accidents. In addition to challenging behaviour, contributing factors included ward routines, shortage of nursing staff, environmental factors and staff knowledge and skills. Nurses tried to secure the patient safety in many different ways, but the modes of actions were insufficient.Conclusion and relevance to clinical practiceNursing staff need evidence‐based information on how to assess the cognitive status of a confused patient and how to encounter such patients. The number of nursing staff and ward routines should be examined critically and put in proportion to the care intensity demands caused by the patient's confused state. The findings can be used as a starting point in the prevention of safety incidents and in improving the care of older patients.