bluuebunny/crossref_metadata_2025 huggingface dataset:
Deranged Calcium Signaling and Neurodegeneration in Spinocerebellar Ataxia Type 2
Authors: Liu Jing , Tang Tie-Shan , Tu Huiping , Nelson Omar , Herndon Emily , Huynh Duong P. , Pulst Stefan M. , Bezprozvanny Ilya
Published: July 2009

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease caused by an expansion of polyglutamine tracts in the cytosolic protein ataxin-2 (Atx2). Cerebellar Purkinje cells (PCs) are predominantly affected in SCA2. The cause of PC degeneration in SCA2 is unknown. Here we demonstrate that mutant Atx2–58Q, but not wild-type (WT) Atx2–22Q, specifically associates with the cytosolic C-terminal region of type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1), an intracellular calcium (Ca2+) release channel. Association with Atx2–58Q increased the sensitivity of InsP3R1 to activation by InsP3in planar lipid bilayer reconstitution experiments. To validate physiological significance of these findings, we performed a series of experiments with an SCA2–58Q transgenic mouse model that expresses human full-length Atx2–58Q protein under the control of a PC-specific promoter. In Ca2+imaging experiments, we demonstrated that stimulation with 3,5-dihydroxyphenylglycine (DHPG) resulted in higher Ca2+responses in 58Q PC cultures than in WT PC cultures. DHPG-induced Ca2+responses in 58Q PC cultures were blocked by the addition of ryanodine, an inhibitor of the ryanodine receptor (RyanR). We further demonstrated that application of glutamate induced more pronounced cell death in 58Q PC cultures than in WT PC cultures. Glutamate-induced cell death of 58Q PC cultures was attenuated by dantrolene, a clinically relevant RyanR inhibitor and Ca2+stabilizer. In whole animal experiments, we demonstrated that long-term feeding of SCA1–58Q mice with dantrolene alleviated age-dependent motor deficits (quantified in beam-walk and rotarod assays) and reduced PC loss observed in untreated SCA2–58Q mice by 12 months of age (quantified by stereology). Results of our studies indicate that disturbed neuronal Ca2+signaling may play an important role in SCA2 pathology and also suggest that the RyanR constitutes a potential therapeutic target for treatment of SCA2 patients.
Medullary Circuitry Regulating Rapid Eye Movement Sleep and Motor Atonia
Authors: Vetrivelan Ramalingam , Fuller Patrick M. , Tong Qingchun , Lu Jun
Published: July 2009

Considerable data support a role for glycinergic ventromedial medulla neurons in the mediation of the postsynaptic inhibition of spinal motoneurons necessary for the motor atonia of rapid-eye movement (REM) sleep in cats. These data are, however, difficult to reconcile with the fact that large lesions of the rostral ventral medulla do not result in loss of REM atonia in rats. In the present study, we sought to clarify which medullary networks in rodents are responsible for REM motor atonia by retrogradely tracing inputs to the spinal ventral horn from the medulla, ablating these medullary sources to determine their effects on REM atonia and using transgenic mice to identify the neurotransmitter(s) involved. Our results reveal a restricted region within the ventromedial medulla, termed here the “supraolivary medulla” (SOM), which contains glutamatergic neurons that project to the spinal ventral horn. Cell-body specific lesions of the SOM resulted in an intermittent loss of muscle atonia, taking the form of exaggerated phasic muscle twitches, during REM sleep. A concomitant reduction in REM sleep time was observed in the SOM-lesioned animals. We next used mice with lox-P modified alleles of either the glutamate or GABA/glycine vesicular transporters to selectively eliminate glutamate or GABA/glycine neurotransmission from SOM neurons. Loss of SOM glutamate release, but not SOM GABA/glycine release, resulted in exaggerated muscle twitches during REM sleep that were similar to those observed after SOM lesions in rats. These findings, together, demonstrate that SOM glutamatergic neurons comprise key elements of the medullary circuitry mediating REM atonia.
Regulation ofKiss1andDynorphinGene Expression in the Murine Brain by Classical and Nonclassical Estrogen Receptor Pathways
Authors: Gottsch Michelle L. , Navarro Víctor M. , Zhao Zhen , Glidewell-Kenney Christine , Weiss Jeffrey , Jameson J. Larry , Clifton Donald K , Levine Jon E. , Steiner Robert A.
Published: July 2009

Kisspeptin is a product of theKiss1gene and is expressed in the forebrain. Neurons that expressKiss1play a crucial role in the regulation of pituitary luteinizing hormone secretion and reproduction. These neurons are the direct targets for the action of estradiol-17β (E2), which acts via the estrogen receptor α isoform (ERα) to regulateKiss1expression. In the arcuate nucleus (Arc), where thedynorphingene (Dyn) is expressed inKiss1neurons, E2inhibits the expression ofKiss1mRNA. However, E2induces the expression ofKiss1in the anteroventral periventricular nucleus (AVPV). The mechanism for differential regulation ofKiss1in the Arc and AVPV by E2is unknown. ERα signals through multiple pathways, which can be categorized as either classical, involving the estrogen response element (ERE), or nonclassical, involving ERE-independent mechanisms. To elucidate the molecular basis for the action of E2onKiss1andDynexpression, we studied the effects of E2onKiss1andDynmRNAs in the brains of mice bearing targeted alterations in the ERα signaling pathways. We found that stimulation ofKiss1expression by E2in the AVPV and inhibition ofDynin the Arc required an ERE-dependent pathway, whereas the inhibition ofKiss1expression by E2in the Arc involved ERE-independent mechanisms. Thus, distinct ERα signaling pathways can differentially regulate the expression of identical genes across different brain regions, and E2can act within the same neuron through divergent ERα signaling pathways to regulate different neurotransmitter genes.
Computational Models of Millisecond Level Duration Tuning in Neural Circuits
Authors: Aubie Brandon , Becker Suzanna , Faure Paul A.
Published: July 2009

Discrimination of stimulus duration on the order of milliseconds has been observed in behavioral and neurophysiological studies across a variety of species and taxa. Several studies conducted in mammals have found neurons in the auditory midbrain (inferior colliculus) that are selective for signal duration. Duration selectivity in these cells arises from an interaction of excitatory and inhibitory events occurring at particular latencies from stimulus onset and offset. As previously shown in barn owls, coincidence of delayed, excitatory events can be used by the CNS to respond selectively to specific stimuli in auditory space. This study formulates several computational models of duration tuning that combine existing conceptual models with observed physiological responses in the auditory brainstem and midbrain to evaluate the plausibility of the proposed neural mechanisms. The computational models are able to reproduce a wide range ofin vivoresponses including best duration tuning, duration-selective response classes, spike counts, first-spike latencies, level tolerance to changes in signal amplitude, and neuropharmacological effects of applying inhibitory neurotransmitter antagonists to duration-tuned neurons. A unified model of duration tuning is proposed that enhances classic models of duration tuning, emphasizes similarities across the models, and simplifies our understanding of duration tuning across species and sensory modalities.
Retina-Specific GTPase Accelerator RGS11/Gβ5S/R9AP Is a Constitutive Heterotrimer Selectively Targeted to mGluR6 in ON-Bipolar Neurons
Authors: Cao Yan , Masuho Ikuo , Okawa Haruhisa , Xie Keqiang , Asami Junko , Kammermeier Paul J. , Maddox Dennis M. , Furukawa Takahisa , Inoue Takayoshi , Sampath Alapakkam P. , Martemyanov Kirill A.
Published: July 2009

Members of the R7 family of the regulators of G-protein signaling (R7 RGS) proteins form multi-subunit complexes that play crucial roles in processing the light responses of retinal neurons. The disruption of these complexes has been shown to lead to the loss of temporal resolution in retinal photoreceptors and deficient synaptic transmission to downstream neurons. Despite the well established role of one member of this family, RGS9-1, in controlling vertebrate phototransduction, the roles and organizational principles of other members in the retina are poorly understood. Here we investigate the composition, localization, and function of complexes containing RGS11, the closest homolog of RGS9-1. We find that RGS11 forms a novel obligatory trimeric complex with the short splice isoform of the type 5 G-protein β subunit (Gβ5) and the RGS9 anchor protein (R9AP). The complex is expressed exclusively in the dendritic tips of ON-bipolar cells in which its localization is accomplished through a direct association with mGluR6, the glutamate receptor essential for the ON-bipolar light response. Although association with both R9AP and mGluR6 contributed to the proteolytic stabilization of the complex, postsynaptic targeting of RGS11 was not determined by its membrane anchor R9AP. Electrophysiological recordings of the light response in mouse rod ON-bipolar cells reveal that the genetic elimination of RGS11 has little effect on the deactivation of Gαoin dark-adapted cells or during adaptation to background light. These results suggest that the deactivation of mGluR6 cascade during the light response may require the contribution of multiple GTPase activating proteins.
Haploinsufficiency ofAFG3L2, the Gene Responsible for Spinocerebellar Ataxia Type 28, Causes Mitochondria-Mediated Purkinje Cell Dark Degeneration
Authors: Maltecca Francesca , Magnoni Raffaella , Cerri Federica , Cox Gregory A. , Quattrini Angelo , Casari Giorgio
Published: July 2009

Paraplegin and AFG3L2 are ubiquitous nuclear-encoded mitochondrial proteins that form hetero-oligomeric paraplegin-AFG3L2 and homo-oligomeric AFG3L2 complexes in the inner mitochondrial membrane, namedm-AAA proteases. These complexes ensure protein quality control in the inner membrane, jointly with a chaperone-like activity on the respiratory chain complexes. Despite coassembling in the same complex, mutations of either paraplegin or AFG3L2 cause two different neurodegenerative disorders. Indeed, mutations of paraplegin are responsible for a recessive form of hereditary spastic paraplegia, whereas mutations of AFG3L2 have been recently associated to a dominant form of spinocerebellar ataxia (SCA28). In this work, we report that the mouse model haploinsufficient forAfg3l2recapitulates important pathophysiological features of the human disease, thus representing the first SCA28 model. Furthermore, we propose a pathogenetic mechanism in which respiratory chain dysfunction and increased reactive oxygen species production caused byAfg3l2haploinsufficiency lead to dark degeneration of Purkinje cells and cerebellar dysfunction.
Coordination of Rhythmic Motor Activity by Gradients of Synaptic Strength in a Neural Circuit That Couples Modular Neural Oscillators
Authors: Smarandache Carmen , Hall Wendy M. , Mulloney Brian
Published: July 2009

Synchronization of distributed neural circuits is required for many behavioral tasks, but the mechanisms that coordinate these circuits are largely unknown. The modular local circuits that control crayfish swimmerets are distributed in four segments of the CNS, but when the swimmeret system is active their outputs are synchronized with a stable intersegmental phase difference of 0.25, an example of metachronal synchronization (Izhikevich, 2007). In each module, coordinating neurons encode detailed information about each cycle of the module's motor output as bursts of spikes, and their axons conduct this information to targets in other segments. This information is both necessary and sufficient for normal intersegmental coordination. In a comprehensive set of recordings, we mapped the synaptic connections of two types of coordinating neurons onto their common target neurons in other segments. Both types of coordinating axons caused large, brief EPSPs in their targets. The shape indices of these EPSPs are tuned to transmit the information from each axon precisely. In each target neuron's own module, these bursts of EPSPs modified the phase of the module's motor output. Each axon made its strongest synapse onto the target neuron in the nearest neighboring segment. Its synapses onto homologous targets in more remote segments were progressively weaker. Each target neuron decodes information from several coordinating axons, and the strengths of their synapses differ systematically. These differences in synaptic strength weight information from each segment differently, which might account for features of the system's characteristic metachronal synchronization.
Extrasynaptic NMDA Receptors Couple Preferentially to Excitotoxicity via Calpain-Mediated Cleavage of STEP
Authors: Xu Jian , Kurup Pradeep , Zhang Yongfang , Goebel-Goody Susan M. , Wu Peter H. , Hawasli Ammar H. , Baum Matthew L. , Bibb James A. , Lombroso Paul J.
Published: July 2009

NMDA receptor (NMDAR)-mediated excitotoxicity plays an important role in several CNS disorders, including epilepsy, stroke, and ischemia. Here we demonstrate the involvement of striatal-enriched protein tyrosine phosphatase (STEP) in this critical process. STEP61is an alternatively spliced member of the family that is present in postsynaptic terminals. In an apparent paradox, STEP61regulates extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, two proteins with opposing functions; activated p38 promotes cell death, whereas activated ERK1/2 promotes cell survival. We found that synaptic stimulation of NMDARs promoted STEP61ubiquitination and degradation, concomitant with ERK1/2 activation. In contrast, extrasynaptic stimulation of NMDARs invoked calpain-mediated proteolysis of STEP61, producing the truncated cleavage product STEP33and activation of p38. The calpain cleavage site on STEP was mapped to the kinase interacting motif, a domain required for substrate binding. As a result, STEP33neither interacts with nor dephosphorylates STEP substrates. A synthetic peptide spanning the calpain cleavage site efficiently reduced STEP61degradation and attenuated p38 activation and cell death in slice models. Furthermore, this peptide was neuroprotective when neurons were subjected to excitotoxicity or cortical slices were exposed to ischemic conditions. These findings suggest a novel mechanism by which differential NMDAR stimulation regulates STEP61to promote either ERK1/2 or p38 activation and identifies calpain cleavage of STEP61as a valid target for the development of neuroprotective therapy.
Protocadherin-α Family Is Required for Serotonergic Projections to Appropriately Innervate Target Brain Areas
Authors: Katori Shota , Hamada Shun , Noguchi Yukiko , Fukuda Emi , Yamamoto Toshifumi , Yamamoto Hideko , Hasegawa Sonoko , Yagi Takeshi
Published: July 2009

Serotonergic axons from the raphe nuclei in the brainstem project to every region of the brain, where they make connections through their extensive terminal arborizations. This serotonergic innervation contributes to various normal behaviors and psychiatric disorders. The protocadherin-α (Pcdha) family of clustered protocadherins consists of 14 cadherin-related molecules generated from a single gene cluster. We found that thePcdhaswere strongly expressed in the serotonergic neurons. To elucidate their roles, we examined serotonergic fibers in a mouse mutant (PcdhaΔCR/ΔCR) lacking thePcdhacytoplasmic region-encoding exons, which are common to the gene cluster. In the first week after birth, the distribution pattern of serotonergic fibers inPcdhaΔCR/ΔCRmice was similar to wild-type, but by 3 weeks of age, when the serotonergic axonal termini complete their arborizations, the distribution of the projections was abnormal. In some target regions, notably the globus pallidus and substantia nigra, the normally even distribution of serotonin axonal terminals was, in the mutants, dense at the periphery of each region, but sparse in the center. In the stratum lacunosum-moleculare of the hippocampus, the mutants showed denser serotonergic innervation than in wild-type, and in the dentate gyrus of the hippocampus and the caudate-putamen, the innervation was sparser. Together, the abnormalities suggested that Pcdha proteins are important in the late-stage maturation of serotonergic projections. Further examination of alternatively spliced exons encoding the cytoplasmic tail showed that the A-type (but not the B-type) cytoplasmic tail was essential for the normal development of serotonergic projections.
Reduced Amyloid Deposition in Mice Overexpressing RTN3 Is Adversely Affected by Preformed Dystrophic Neurites
Authors: Shi Qi , Prior Marguerite , He Wanxia , Tang Xiangying , Hu Xiangyou , Yan Riqiang
Published: July 2009

Reticulon 3 (RTN3) was initially identified as a negative modulator of BACE1, an enzyme that cleaves amyloid precursor protein (APP) to release β-amyloid peptide. Interestingly, RTN3 can also form aggregates after accumulation, and increased RTN3 aggregation correlates with the formation of RTN3 immunoreactive dystrophic neurites (RIDNs) in brains of Alzheimer's cases. Transgenic mice expressing RTN3 alone develop RIDNs in their hippocampus but not in their cortex. To determine thein vivoeffects of RTN3 and preformed RIDNs on amyloid deposition, we crossed bitransgenic mice expressing APP and presenilin 1 (PS1) mutations with mice overexpressing RTN3. We found that amyloid deposition in cortex, the hippocampal CA3 region, and dentate gyrus was significantly reduced in triple transgenic mice compared with bitransgenic controls. However, reduction of amyloid deposition in the hippocampal CA1 region, where RIDNs predominantly formed before amyloid deposition, was less significant. Hence, preformed RTN3 aggregates in RIDNs clearly offset the negative modulation of BACE1 activity by RTN3. Furthermore, our study indicates that the increased expression of RTN3 could result in an alteration of BACE1 intracellular trafficking by retaining more BACE1 in the endoplasmic reticulum compartment where cleavage of APP by BACE1 is less favored. Our results suggest that inhibition of RTN3 aggregation is likely to be beneficial by reducing both amyloid deposition and the formation RIDNs.
Flexible Scheduling and the Gender Wage Gap
Authors: Winder Katie L
Published: July 2009

Using British data from the 2004 Workplace Employment Relations Survey, the author examines whether and how the relationship between schedule flexibility and wages differs by gender. Using a basic measure of whether the worker has discretion over the start and end times of work, men have more than twice the wage return to flexibility than do women, even within the same firm and detailed occupation. This difference cannot be explained by differences in household responsibilities or by differences in part time work by gender, but gender differences in job authority and autonomy do matter. Differences in the wage returns to this type of flexibility account for 10% of the gender wage gap, which suggests that understanding the underlying cause for the disparity in the returns to flexibility is important for understanding the policy implications of promoting flexible work arrangements.
Using the PubMatrix Literature-Mining Resource to Accelerate Student-Centered Learning in a Veterinary Problem-Based Learning Curriculum
Authors: David John , Irizarry Kristopher J.L.
Published: July 2009

Problem-based learning (PBL) creates an atmosphere in which veterinary students must take responsibility for their own education. Unlike a traditional curriculum where students receive discipline-specific information by attending formal lectures, PBL is designed to elicit self-directed, student-centered learning such that each student determines (1) what he/she does not know (learning issues), (2) what he/she needs to learn, (3) how he/she will learn it, and (4) what resources he/she will use. One of the biggest challenges facing students in a PBL curriculum is efficient time management while pursuing learning issues. Bioinformatics resources, such as the PubMatrix literature-mining tool, allow access to tremendous amounts of information almost instantaneously. To accelerate student-centered learning it is necessary to include resources that enhance the rate at which students can process biomedical information. Unlike using the PubMed interface directly, the PubMatrix tool enables users to automate queries, allowing up to 1,000 distinct PubMed queries to be executed per single PubMatrix submission. Users may submit multiple PubMatrix queries per session, resulting in the ability to execute tens of thousands of PubMed queries in a single day. The intuitively organized results, which remain accessible from PubMatrix user accounts, enable students to rapidly assimilate and process hundreds of thousands of individual publication records as they relate to the student's specific learning issues and query terms. Subsequently, students can explore substantially more of the biomedical publication landscape per learning issue and spend a greater fraction of their time actively engaged in resolving their learning issues.
The Transition from Veterinary Student to Practitioner: A “Make or Break” Period
Authors: Gilling Marg L. , Parkinson Timothy J.
Published: July 2009

This paper examines the transition from veterinary student to practitioner, in the context of assessing the outcomes of the veterinary degree program in which the students were trained. Questionnaires were sent to all registered veterinarians who graduated from Massey University between 2001 and 2003 and the heads of human resources of all veterinary practices in New Zealand. These groups, together with veterinarians who had graduated from Massey University between 1993 and 2000, were also invited to participate in focus groups or interviews. Replies were received from 64 graduates and 114 employers. In addition, 115 veterinarians were interviewed or joined focus groups. Most participants thought that the veterinary degree program at Massey University provided a strong basis in scientific theory and clinical reasoning, but was lacking in communication skills training. Clinical exposure was regarded as less than optimal, but adequate for starting practice and as much as could be achieved within the duration of the program. Graduates and employers both recognized the pivotal importance of the first year in practice in the careers of veterinarians. Most graduates had positive experiences of their first year, but for those whose experiences were negative, they were often strongly so. Situations in which confidence and clinical competence could be developed in a supportive environment were associated with positive outcomes. The first year after graduation was regarded by graduates and employers as a “make or break” period. Many of the changes that the veterinary profession is currently experiencing, particularly in terms of the demographics of its entrants, impact upon this first post–graduation year.
Veterinary Professional Associates: Does the Profession's Foresight Include a Mid-Tier Professional Similar to Physician Assistants?
Authors: Kogan Lori R. , Stewart Sherry M.
Published: July 2009

The projected shortage of veterinarians has created a need to explore alternatives designed to meet society's future demands. A veterinary professional health care provider, similar to the human medical profession's physician assistant (PA), is one such alternative. To explore this option, this paper provides background information on the development of PAs, including the motivations behind the initiative and the history of the role's development. Rather than aiming for a persuasive appeal, the authors have written this article with the intent of fostering discussion. It is suggested that perhaps veterinary professional associates, modeled after PAs, could be employed to handle routine veterinary care and thereby allow veterinarians additional time to focus on the more demanding and challenging aspects of veterinary medicine. Perhaps a team approach, similar to the physician/PA team, could help the field of veterinary medicine to better serve both clients and patients. As veterinary medicine directs its attention toward the new challenges on the horizon, creative solutions will be needed. Perhaps some variation of a veterinary professional associate is worthy of future discussion.
A Retrospective Analysis of Veterinary Medical Curriculum Development in The Netherlands
Authors: Jaarsma Debbie A.D.C. , Scherpbier Albert J.J.A. , Beukelen Peter van
Published: July 2009

Over the past two decades, the Faculty of Veterinary Medicine of Utrecht University (FVMU) has introduced major curriculum changes to keep pace with modern veterinary educational developments worldwide. Changes to program outcomes have been proposed according to professional and societal demands, with more attention paid to generic competencies and electives and species/sector differentiation. Furthermore, changes in educational approaches and the educational organization have been proposed, aiming at a transition from teacher-centered education toward more student-centered education. Curriculum development is a complex and difficult process, with many elements interacting. For a new curriculum to become valid, curriculum elements and their interrelation—such as statements of intent (also called outcomes, goals, or objectives), content, teaching and learning strategies, assessment strategies, and context—need to be addressed in the educational philosophy (i.e., the intended curriculum). This paper describes a document analysis of the major curriculum reforms of the FVMU. Curriculum committee reports were critically analyzed to gain insight into the intentions of the curriculum designers and the match between the curriculum elements, as described by Prideaux. The results show that the reports paid considerable attention to generic competency training, especially to academic training, and to the introduction of more student-centered teaching and learning strategies. However, little attention was paid to assessment strategies and the statements of intent were defined rather broadly. Curriculum evaluation (i.e., what is delivered to the students and how is the curriculum experienced) is needed at all curriculum levels. Possible mismatches between levels need to be identified.
Subgrain boundaries and related microstructural features in EDML (Antarctica) deep ice core
Authors: Weikusat Ilka , Kipfstuhl Sepp , Faria Sérgio H. , Azuma Nobuhiko , Miyamoto Atsushi
Published: July 2009

Subgrain boundaries revealed as shallow sublimation grooves on ice sample surfaces are a direct and easily observable feature of intracrystalline deformation and recrystallization. Statistical data obtained from the EPICA Dronning Maud Land (EDML) deep ice core drilled in East Antarctica cannot detect a depth region of increased subgrain-boundary formation. Grain-boundary morphologies show a strong influence of internal strain energy on the microstructure at all depths. The data do not support the classical view of a change of dominating recrystallization regimes with depth. Three major types of subgrain boundaries, reflecting high mechanical anisotropy, are specified in combination with crystal-orientation analysis.
Glacial rumblings from Jakobshavn ice stream, Greenland
Authors: Rial J.A. , Tang C. , Steffen K.
Published: July 2009

The steep increase in Greenland’s glacial earthquake activity detected by the Global Seismographic Network since the late 1990s suggests that a close inspection of these events might provide clues to the nature and origin of such seismic activity. Here we discuss the detection of large, unexpected seismic events of extraordinarily long duration (10–40 min) occurring about once every 2 days, and localized in the ice stream that feeds the Earth’s fastest-moving glacier (Jakobshavn Isbræ) from the east. These ‘glacial rumblings’ represent an ice-mass wasting process that is greater and more frequent than glacial earthquakes have suggested. Probably triggered by calving, the rumblings are all very similar regardless of duration, and all end with a sharp, earthquake-like event in which the largest seismic amplitude is in the rumbling and that might signal the collapse of large ice masses upstream. By calculating the total amount of seismic energy released as rumblings, we estimate that the maximum seasonal amount of ice moved seismogenically down the ice stream is up to 12 km3, or ∼30% of the average annual iceberg discharge in Jakobshavn.
Airborne radar sounder for temperate ice: initial results from Patagonia
Authors: Zamora Rodrigo , Ulloa David , Garcia Gonzalo , Mella Ronald , Uribe José , Wendt Jens , Rivera Andrés , Gacitúa Guisella , Casassa Gino
Published: July 2009

We describe the development of a low-frequency airborne radar specifically designed for the sounding of temperate ice. The system operates at a central frequency of 1 MHz and consists of an impulse transmitter with an output voltage up to 5000 V and a digital receiver with a maximum gain of 80 dB. The radar was deployed on board a CASA 212 aircraft, which also carries a laser altimeter, an inertial navigation system, a digital camera and a GPS receiver. A description of the radar system is provided, as well as preliminary results obtained at Glaciar Tyndall, Campo de Hielo Sur (Southern Patagonia Icefield), where an ice depth of 670 m was reached.
Calving icebergs indicate a thick layer of temperate ice at the base of Jakobshavn Isbræ, Greenland
Authors: Lüthi Martin P. , Fahnestock Mark , Truffer Martin
Published: July 2009

The puzzling fact that Jakobshavn Isbræ, West Greenland, is flowing very fast but without any significant seasonal velocity changes, despite big amounts of surface-derived meltwater entering the ice stream (Echelmeyer and Harrison, 1990), has been explained by a combination of different types of measurements. It is now well established from seismic measurements and radio-echo sounding that Jakobshavn Isbræ flows through a deeply eroded subglacial trench that, even 50 km inland of the grounding line, extends as far as 1500 m below sea level (Clarke and Echelmeyer, 1996; Legarsky and Huang, 2006). Temperature measurements in boreholes down to 65% of the 2500 m thick ice stream at site B, some 50 km upstream of the calving front (Fig. 1b; Iken and others, 1993), were used to infer the presence of a substantial layer of temperate ice, the thickness of which was estimated to be at least 300 m by modeling and matching internal layering structures (Funk and others, 1994; Lüthi and others, 2002). The presence of a thick layer of temperate ice under very high driving stress allows for high ice-deformation rates, which contribute substantially to the observed fast flow velocities. Basal motion, while certainly important, seems to be barely influenced by the seasonal meltwater input (Echelmeyer and Harrison, 1990).
Thermal convection and the origin of ice streams
Authors: Hughes T.
Published: July 2009

Ice streams are a fact of ice-sheet dynamics, draining up to 90% of the ice. Thermal convection in ice below the density inversion is a speculation. An attempt is made to meld the two in such a way that the speculation becomes an explanation for the fact.
Calculation of glacier volume from sparse ice-thickness data, applied to Schaufelferner, Austria
Authors: Fischer Andrea
Published: July 2009

In order to develop and evaluate a method for the determination of glacier volume from ice-thickness data, the volume of Schaufelferner, Austria, is calculated (1) by manual interpolation of ground-penetrating radar (GPR) data based on measurements at 36 locations in 1995, (2) by manual interpolation of 144 GPR measurements acquired for a higher-resolution estimate in 2003 and 2006, (3) by multiplying the mean of the measured ice-thickness data by the glacier area, (4) by automatic kriging of the 1995 GPR data and (5) by application of area/volume scaling algorithms to the Austrian glacier inventory data of 1969, 1997 and 2006. The so determined glacier volumes are compared with the ice-volume changes calculated from digital elevation models (DEMs) of the Austrian glacier inventories. The manually interpolated volumes based on the 1995 and 2003/06 GPR data yielded a volume loss only slightly different from volume loss calculated from the glacier inventories of 1997 and 2007. Other methods were not able to reproduce the volume losses of the glacier inventory DEMs. To assess the accuracy of deriving ice-thickness changes with GPR, repeated ice-thickness measurements at the same locations were carried out between 2005 and 2008.
A method to estimate the ice volume and ice-thickness distribution of alpine glaciers
Authors: Farinotti Daniel , Huss Matthias , Bauder Andreas , Funk Martin , Truffer Martin
Published: July 2009

Sound knowledge of the ice volume and ice-thickness distribution of a glacier is essential for many glaciological applications. However, direct measurements of ice thickness are laborious, not feasible everywhere and necessarily restricted to a small number of glaciers. In this paper, we present a method to estimate the ice-thickness distribution and the total ice volume of alpine glaciers. This method is based on glacier mass turnover and principles of ice-flow mechanics. The required input data are the glacier surface topography, the glacier outline and a set of borders delineating different ‘ice-flow catchments’. Three parameters describe the distribution of the ‘apparent mass balance’, which is defined as the difference between the glacier surface mass balance and the rate of ice-thickness change, and two parameters define the ice-flow dynamics. The method was developed and validated on four alpine glaciers located in Switzerland, for which the bedrock topography is partially known from radio-echo soundings. The ice thickness along 82 cross-profiles can be reproduced with an average deviation of about 25% between the calculated and the measured ice thickness. The cross-sectional areas differ by less than 20% on average. This shows the potential of the method for estimating the ice-thickness distribution of alpine glaciers without the use of direct measurements.
Value Theory in Ecological Economics: The Contribution of a Political Economy of Wealth
Authors: Douai Ali
Published: July 2009

This paper demonstrates how a Political Economy of Wealth – an analytical framework inspired from Ricardo's and Marx's theories of value – strengthens the analytical force of Socio-Ecological Economics in the context of the controversy over the value of nature. The Political Economy of Wealth helps (1) to overcome some theoretical limitations encountered in Socio-Ecological Economics, (2) to develop a critical perspective on neoclassical theory of environmental values, as well as a new justification of value incommensurability, and (3) to move toward a new research agenda that aims to study interactions between the economy and the environment from a socio-historical perspective.
Editor's Note for Vol.4
Authors: Rafique Abu Bakr
Published: July 2009

doi: 10.3329/iiucs.v4i0.2687   IIUC STUDIES Vol. - 4, December 2007
Managerial Leadership: An Islamic Perspective
Authors: Ather Syed Mohammad , Sobhani Farid Ahammad
Published: July 2009

Islam is the guide to eradicate all problems in our social life. Allah (Swt) has addressed the believers as Ummah, which implies the necessity of leadership in Islam. Allah says to his Prophet Mohammad (Sm) "...I have perfected your religion for you, completed My favor upon you, and have chosen for you Islam as your religion" (Surah Al-Maidah). Mohammad (Sm) says "Every one of you is a shepherd and every one of you is responsible for what he is shepherd of" (Sahih Al Bukhari). Islam as a complete code of life has a set of principles, guidelines for managers to lead the human resources in an organization. This study is an attempt to find out the basic guidelines laid down in Islam for managerial leadership. It has pointed out the operational principles of managerial leadership, managerial grid theory, leadership continuum, team building- team spirit and qualities of a managerial leader from the Islam perspective.   doi: 10.3329/iiucs.v4i0.2688     IIUC STUDIES Vol. - 4, December 2007 (p 7-24)
The impact of the First World War on the poetry of Wilfred Owen
Authors: Mahmud Mohammad Riaz
Published: July 2009

In 1914 the First World War broke out on a largely innocent world, a world that still associated warfare with glorious cavalry charges and the noble pursuit of heroic ideals. This was the world's first experience of modern mechanized warfare. As the months and years passed, each bringing increasing slaughter and misery, the soldiers became increasingly disillusioned. Many of the strongest protests made against the war were made through the medium of poetry by young men horrified by what they saw. They not only wrote about the physical pain of wounds and deaths, but also the mental pain that were consequences of war. One of these poets was Wilfred Owen. In his poetry we find the feelings of futility, horror, and dehumanization that he encountered in war.   doi: 10.3329/iiucs.v4i0.2689      IIUC STUDIES Vol. - 4, December 2007 (p 25-40)
The Lyrical Strain in Victorian Poetry
Authors: Huda Md Nazmul
Published: July 2009

This article is an attempt to explore the lyrical strain in Victorian Poetry1. It has been demonstrated that lyrical strain is the combination of subjectivity and melody. Some particular lyric poems of Victorian period have been studied with the help of the views and comments of some critics so that better comprehension of the lyrics as well as the poets may be carried out. Lyrical allusions and references have been drawn from the poems of Tennyson, Arnold and Rossetti to present how the sources of their lyricism vary from one another. In presenting the lyrical features of their poems, the critical method followed is based upon comparison and contrast. Since literature is deemed to be the reflection of life, this study may help the readers understand sentiments and emotions of men and women of that particular period.   doi: 10.3329/iiucs.v4i0.2691      IIUC STUDIES Vol. - 4, December 2007 (p 49-58)
Translation of the Holy Quran and the Role of Orientalist
Authors: Shouk SA
Published: July 2009

The full text of this article is in Arabic - see PDF below.doi: 10.3329/iiucs.v4i0.2862 IIUC STUDIES Vol. - 4, December 2007 (p 57-74)
Genistein Inhibition of Topoisomerase IIα Expression Participated by Sp1 and Sp3 in HeLa Cell
Authors: Zhou Najing , Yan Yunli , Li Wenling , Wang Yanling , Zheng Lifen , Han Shuo , Yan Yongxin , Li Yunzhi
Published: July 2009

Genistein (4′, 5, 7-trihydroxyisoflavone) is an isoflavone compound obtained from plants that has potential applications in cancer therapy. However, the molecular mechanism of the action of genistein on cancer cell apoptosis is not well known. In this study, we investigated the effect of genistein on topoisomerase II-α (Topo IIα), an important protein involved in the processes of DNA replication and cell proliferation. The results revealed that inhibition of Topo IIα expression through the regulation of Specificity protein 1 and Specificity protein 3 may be one of the reasons for genistein’s induction of HeLa cell apoptosis.
Brominated Selinane Sesquiterpenes from the Marine Brown Alga Dictyopteris divaricata
Authors: Ji Nai-Yun , Wen Wei , Li Xiao-Ming , Xue Qin-Zhao , Xiao Hua-Ling , Wang Bin-Gui
Published: July 2009

Two new brominated selinane sesquiterpenes, 1-bromoselin-4(14),11-diene (1) and 9-bromoselin-4(14),11-diene (2), one known cadinane sesquiterpene, cadalene (3), and four known selinane sesquiterpenes, α-selinene (4), β-selinene (5), β-dictyopterol (6), and cyperusol C (7), were isolated from a sample of marine brown alga Dictyopteris divaricata collected off the coast of Yantai (China). Their structures were established by detailed MS and NMR spectroscopic analysis, as well as comparison with literature data.
Electronic Structure of the Azide Group in 3¢-Azido-3¢-deoxythymidine (AZT) Compared to Small Azide Compounds
Authors: Chen Fang-Fang , Wang Feng
Published: July 2009

Theoretical calculations for some structural and electronic properties of the azide moiety in the nucleoside reverse transcriptase (RT) inhibitor 3¢-azido-3¢-deoxythymidine (AZT) are reported. These properties, which include geometrical properties in three dimensional space, Hirshfeld charges, electrostatic potential (MEP), vibrational frequencies, and core and valence ionization spectra, are employed to study how the azide group is affected by the presence of a larger fragment. For this purpose, two small but important organic azides, hydrazoic acid and methyl azide, are also considered. The general features of trans Cs configuration for RNNN fragments[1] is distorted in the large AZT bio-molecule. Hirshfeld charge analysis shows charges are reallocated more evenly on azide when the donor group R is not a single atom. Infrared and photoelectron spectra reveal different aspects of the compounds. In conclusion, the electronic structural properties of the compounds depend on the specific property, the local structure and chemical environment of a species.
18F-FDG PET for detecting metastases and synchronous primary malignancies in patients with oral and oropharyngeal cancer
Authors: Wallowy P. , Diener J. , Grünwald F. , Kovács A. F.
Published: July 2009

Aim: Assessment of the efficiency of 18F-FDGPET (PET) for the detection of distant metastases and synchronous primary malignancies in patients with oral and oropharyngeal squamous cell cancer (OOSCC). Patients, methods: Retrospective evaluation of PET studies of 422 patients with histologically confirmed OOSCC. 99 patients (23.5%) demonstrated a suspect distant finding of whom 84 could be interdisciplinary evaluated and consecutively confirmed or refuted by other diagnostic modalities or biopsy. Results: In 74 of 80 evaluable cases, PET showed the primary tumour (92.5%). 26/84 suspect distant lesions (31%) showed by means of PET were confirmed to be malignancies (mean SUV 3.96; range 1.4-9.37). Main sites were the lung, the upper aerodigestive tract, and the gastrointestinal system. In the other 58 cases (69%), where the suspect lesions were confirmed as benign, mean SUV was 2.65 (range 0.7–6.5) (difference statistically significant). The SUV above which every suspect finding was proven to be of malignant condition was 6.5 (specificity 100%, sensitivity 38%, accuracy 81%). Conclusion: PET may have an important role in initial staging and the detection of distant metastases and synchronous primary malignancies. Setting a SUV threshold for determining malignancies can support interpretation. In borderline cases, however, interdisciplinary evaluation by means of other diagnostic modalities remains crucial.
ERas is Expressed in Primate Embryonic Stem Cells but not Related to Tumorigenesis
Authors: Tanaka Yujiro , Ikeda Tamako , Kishi Yukiko , Masuda Shigeo , Shibata Hiroaki , Takeuchi Kengo , Komura Makoto , Iwanaka Tadashi , Muramatsu Shin-Ichi , Kondo Yasushi , Takahashi Kazutoshi , Yamanaka Shinya , Hanazono Yutaka
Published: July 2009

The ERas gene promotes the proliferation of and formation of teratomas by mouse embryonic stem (ES) cells. However, its human orthologue is not expressed in human ES cells. This implies that the behavior of transplanted mouse ES cells would not accurately reflect the behavior of transplanted human ES cells and that the use of nonhuman primate models might be more appropriate to demonstrate the safety of human ES cell-based therapies. However, the expression of the ERas gene has not been examined in nonhuman primate ES cells. In this study, we cloned the cynomolgus homologue and showed that the ERas gene is expressed in cynomolgus ES cells. Notably, it is also expressed in cynomolgus ES cell-derived differentiated progeny as well as cynomolgus adult tissues. The ERas protein is detectable in various cynomolgus tissues as assessed by immunohistochemisty. Cynomolgus ES cell-derived teratoma cells, which also expressed the ERas gene at higher levels than the undifferentiated cynomolgus ES cells, did not develop tumors in NOD/Shi- scid, IL-2Rγnull (NOG) mice. Even when the ERas gene was overexpressed in cynomolgus stromal cells, only the plating efficiency was improved and the proliferation was not promoted. Thus, it is unlikely that ERas contributes to the tumorigenicity of cynomolgus cells. Therefore, cynomolgus ES cells are more similar to human than mouse ES cells despite that ERas is expressed in cynomolgus and mouse ES cells but not in human ES cells.
Transplantation of Allogeneic and Xenogeneic Placenta-Derived Cells Reduces Bleomycin-Induced Lung Fibrosis
Authors: Cargnoni Anna , Gibelli Lucia , Tosini Alessandra , Signoroni Patrizia Bonassi , Nassuato Claudia , Arienti Davide , Lombardi Guerino , Albertini Alberto , Wengler Georg S. , Parolini Ornella
Published: July 2009

Fetal membranes (amnion and chorion) have recently raised significant attention as potential sources of stem cells. We have recently demonstrated that cells derived from human term placenta show stem cell phenotype, high plasticity, and display low immunogenicity both in vitro and in vivo. Moreover, placenta-derived cells, after xenotransplantation, are able to engraft in solid organs including the lung. On these bases, we studied the effects of fetal membrane-derived cells on a mouse model of bleomycin-induced lung fibrosis. Fetal membrane-derived cells were infused 15 min after intratracheal bleomycin instillation. Different delivery routes were used: intraperitoneal or intratracheal for both xenogeneic and allogeneic cells, and intravenous for allogeneic cells. The effects of the transplanted cells on bleomycin-induced inflammatory and fibrotic processes were then scored and compared between transplanted and control animals at different time points. By PCR and immunohistochemistry analyses, we demonstrated the presence of transplanted cells 3, 7, 9, and 14 days after transplantation. Concomitantly, we observed a clear decrease in neutrophil infiltration and a significant reduction in the severity of bleomycin-induced lung fibrosis in mice treated with placenta-derived cells, irrespective of the source (allogeneic or xenogeneic) or delivery route. Our findings constitute further evidence in support of the hypothesis that placenta-derived cells could be useful for clinical application, and warrant further studies toward the use of these cells for the repair of tissue damage associated with inflammatory and fibrotic degeneration.
Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity
Authors: Khunnawutmanotham Nisachon , Chimnoi Nitirat , Thitithanyanont Arunee , Saparpakorn Patchreenart , Choowongkomon Kiattawee , Pungpo Pornpan , Hannongbua Supa , Techasakul Supanna
Published: July 2009

Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.