bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular pathogenesis of malignant mesothelioma
Authors: Rascoe Philip A. , Jupiter Daniel , Cao Xiaobo , Littlejohn James E. , Smythe W. Roy
Published: May 2012

Malignant mesothelioma is a rare, highly aggressive cancer arising from mesothelial cells that line the pleural cavities. Approximately 80% of mesothelioma cases can be directly attributed to asbestos exposure. Additional suspected causes or co-carcinogens include other mineral fibres, simian virus 40 (SV40) and radiation. A mesothelioma epidemic in Turkey has demonstrated a probable genetic predisposition to mineral fibre carcinogenesis and studies of human tissues and animal models of mesothelioma have demonstrated genetic and epigenetic events that contribute to the multistep process of mineral fibre carcinogenesis. Several growth factors and their receptors have a significant role in the oncogenesis, progression and resistance to therapy of mesothelioma. Epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF) have been shown as targets for therapy based on promising preclinical data. However, clinical trials of tyrosine kinase inhibitors in mesothelioma have been disappointing. Bcl-XL is an important antiapoptotic member of the Bcl-2 family and is overexpressed in several solid tumours, including mesothelioma. Reduction of Bcl-XL expression in mesothelioma induces apoptosis and engenders sensitisation to cytotoxic chemotherapeutic agents. Pharmacological inhibitors of antiapoptotic Bcl-2 family members continue to undergo refinement and have shown promise in mesothelioma.
Flotation and free surface flow in a model for subglacial drainage. Part 1. Distributed drainage
Authors: Schoof Christian , Hewitt Ian J. , Werder Mauro A.
Published: May 2012

We present a continuum model for melt water drainage through a spatially distributed system of connected subglacial cavities, and consider in this context the complications introduced when effective pressure or water pressure drops to zero. Instead of unphysically allowing water pressure to become negative, we model the formation of a partially vapour- or air-filled space between ice and bed. Likewise, instead of allowing sustained negative effective pressures, we allow ice to separate from the bed at zero effective pressure. The resulting model is a free boundary problem in which an elliptic obstacle problem determines hydraulic potential, and therefore also determines regions of zero effective pressure and zero water pressure. This is coupled with a transport problem for stored water, and the coupled system bears some similarities with Hele-Shaw and squeeze-film models. We present a numerical method for computing time-dependent solutions, and find close agreement with semi-analytical travelling wave and steady-state solutions. As may be expected, we find that ice–bed separation is favoured by high fluxes and low ice surface slopes and low bed slopes, while partially filled cavities are favoured by low fluxes and high slopes. At the boundaries of regions with zero water or effective pressure, discontinuities in water level are frequently present, either in the form of propagating shocks or as stationary hydraulic jumps accompanied by discontinuities in potential gradient.
Flotation and free surface flow in a model for subglacial drainage. Part 2. Channel flow
Authors: Hewitt I. J. , Schoof C. , Werder M. A.
Published: May 2012

We present a new model of subglacial drainage incorporating flow in a network of channels and a porous sheet, with water exchange between the two determined by pressure gradients. The sheet represents the average effect of many linked cavities, whilst the channels emerge from individual cavities that enlarge due to dissipation-induced melting. The model distinguishes cases when the water pressure drops to zero, in which case it allows for the drainage space to be only partially filled with water (free surface flow), and when the pressure reaches the ice overburden pressure, in which case it allows for uplift of the ice to whatever extent is needed to accommodate the water (flotation). Numerical solutions are found for a one-dimensional flow-line version of the model. The results capture typically observed or inferred features of subglacial drainage systems, including open channel flow at the ice margin, seasonal channel evolution, and high water pressures and uplift of the ice surface driven by rapid changes in water supply.
Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study
Authors: Sarkar S. , Craig M. C. , Catani M. , Dell'Acqua F. , Fahy T. , Deeley Q. , Murphy D. G. M.
Published: May 2012

Background

Children with conduct disorder (CD) are at increased risk of developing antisocial personality disorder (ASPD) and psychopathy in adulthood. The biological basis for this is poorly understood. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of psychopathic antisocial adults reported significant differences from controls in the fractional anisotropy (FA) of the uncinate fasciculus (UF), a white-matter tract that connects the amygdala to the frontal lobe. However, it is unknown whether developmental abnormalities are present in the UF of younger individuals with CD.

Method

We used DT-MRI tractography to investigate, for the first time, the microstructural integrity of the UF in adolescents with CD, and age-related differences in this tract. We compared FA and perpendicular diffusivity of the UF in 27 adolescents with CD and 16 healthy controls (12 to 19 years old) who did not differ significantly in age, IQ or substance use history. To confirm that these findings were specific to the UF, the same measurements were extracted from two non-limbic control tracts. Participants in the CD group had a history of serious aggressive and violent behaviour, including robbery, burglary, grievous bodily harm and sexual assault.

Results

Individuals with CD had a significantly increased FA (p = 0.006), and reduced perpendicular diffusivity (p = 0.002), in the left UF. Furthermore, there were significant age-related between-group differences in perpendicular diffusivity of the same tract (Zobs = 2.40, p = 0.01). Controls, but not those with CD, showed significant age-related maturation. There were no significant between-group differences in any measure within the control tracts.

Conclusions

Adolescents with CD have significant differences in the ‘connectivity’ and maturation of UF.
The role of the amygdala in the appraising brain
Authors: Sander David
Published: May 2012

Lindquist et al. convincingly argue that the brain implements psychological operations that are constitutive of emotion rather than modules subserving discrete emotions. However, thenatureof such psychological operations is open to debate. I argue that considering appraisal theories may provide alternative interpretations of the neuroimaging data with respect to the psychological operations involved.
HEALTH TECHNOLOGY ASSESSMENT IN POLAND AND SCOTLAND: COMPARISON OF PROCESS AND DECISIONS
Authors: Kolasa Katarzyna , Wasiak Radek
Published: May 2012

Objectives: We compared Polish and Scottish Health Technology Assessment (HTA) process in order to elicit recommendations for future development of HTA methodological guidelines in Poland.

Methods: We studied the differences between Polish and Scottish HTA methodological guidelines. HTA recommendations issued by Polish HTA agency (AHTAPol) in the period January 1 through December 31, 2008, were benchmarked to HTA guidance published by Scottish Medical Consortium (SMC) for the same drug technology.

Results: The Scottish HTA methodological guidelines were more instructive in terms of clinical and economic evaluations than Polish guidelines. SMC evaluated forty-eight of sixty-eight drug technologies appraised by AHTAPoL. There were thirty drug technologies that received similar guidance in both countries and eighteen with contradictory HTA recommendations. In Scotland, there were more positive HTA recommendations than there were in Poland. While comments about efficacy or safety were commonplace among reasons for negative recommendations in Poland, insufficient justification of treatment's cost in relation to benefits was the most often cited reason for rejection in Scotland. SMC tended to recommend restricted use to specific sub-populations for several drug technologies negatively appraised by AHTAPoL.

Conclusions: The comparison between SMC and AHTAPoL suggests that there is potential room of improvement of the Polish HTA methodological guidelines. Comparative effectiveness and safety, subgroup analysis, and adaptation of models to local settings were identified as key areas for further development of Polish HTA methodological guidelines.
Episcopal Lineage: A Theological Reflection on Blake v Associated Newspapers Ltd
Authors: Hill Christopher
Published: May 2012

Mathew's varied ecclesiastical progress presents a fascinating case study of an episcopate detached from a main-stream Christian community and alerts us to the danger of solely considering ‘episcopal lineage‘ as the litmus test for apostolicity. Mathew was born in France in 1852 and baptised a Roman Catholic; due to his mother's scruples he was soon re-baptised in the Anglican Church. He studied for the ministry in the Episcopal Church of Scotland, but sought baptism again in the Church of Rome, into which he was ordained as a priest in Glasgow in 1877. He became a Dominican in 1878, but only persevered a year, moving around a number of Catholic dioceses: Newcastle, Plymouth, Nottingham and Clifton. Here he came across immorality, and became a Unitarian. He next turned to the Church of England and the Diocese of London, but was soon in trouble for officiating without a licence. In 1890 he put forward his claim to Garter King of Arms for the title of 4th Earl of Llandaff of Thomastown, Co. Tipperary. He renounced the Church of England in 1899 because of vice. After founding a zoo in Brighton, which went bankrupt, he appeared in court in connection with a charge of embezzlement. He then became a Roman Catholic again, now as a layman.
Thinking a Bow-and-arrow Set: Cognitive Implications of Middle Stone Age Bow and Stone-tipped Arrow Technology
Authors: Lombard Marlize , Haidle Miriam Noël
Published: May 2012

For various reasons increased effort has recently been made to detect the early use of mechanically-projected weaponry in the archaeological record, but little effort has yet been made to investigate explicitly what these tool sets could indicate about human cognitive evolution. Based on recent evidence for the use of bow-and-arrow technology during the Middle Stone Age in southern Africa by 64 kya, we use the method of generating and analysing cognigrams and effective chains to explore thought-and-action sequences associated with this technology. We show that, when isolated, neither the production of a simple bow, nor that of a stone-tipped arrow, can be reasonably interpreted to indicate tool behaviour that is cognitively more complex than the composite artefacts produced by Neanderthals or archaic modern Homo. On the other hand, as soon as a bow-and-arrow set is used as an effective group of tools, a novel cognitive development is expressed in technological symbiosis, i.e. the ability to conceptualize a set of separate, yet inter-dependent tools. Such complementary tool sets are able to unleash new properties of a tool, inconceivable without the active, simultaneous manipulation of another tool. Consequently, flexibility regarding decision-making and taking action is amplified. The archaeological evidence for such amplified conceptual and technological modularization implies a range of cognitive and behavioural complexity and flexibility that is basic to human behaviour today.
Effects of HIV and Early Life Stress on Amygdala Morphometry and Neurocognitive Function
Authors: Clark Uraina S. , Cohen Ronald A. , Sweet Lawrence H. , Gongvatana Assawin , Devlin Kathryn N. , Hana George N. , Westbrook Michelle L. , Mulligan Richard C. , Jerskey Beth A. , White Tara L. , Navia Bradford , Tashima Karen T.
Published: May 2012

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N= 20); HC High-ELS (N= 27); HIV+ Low-ELS (N= 24); HIV+ High-ELS (N= 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals. (JINS, 2012,19, 1–12)
‘[W]e Find Families for Children, Not Children for Families’: An Incident in the Long and Unhappy History of Relations between Social Workers and Adoptive Parents
Authors: Quartly Marian
Published: May 2012

Relatively little work on adoption focuses on the role of social workers. This article gives an account of the conflict between social workers and prospective adoptive parents which developed in Australia in the 1970s, taking as a case study the conflicting roles of adoptive parent advocates and professional social workers within the Standing Committee on Adoption in the Australian state of Victoria. Its overarching concern lies with the historical attitudes of the social work profession towards adoption, both domestic and intercountry, as these have changed from an embrace of both adoption and adoptive parents to mutual alienation. It concludes that the inclusive practice of radical social work could only briefly contain contesting client groups.
Intercountry Adoption and the Inappropriate/d Other: Refusing the Disappearance of Birth Families
Authors: Riggs Damien W.
Published: May 2012

Dominant social norms relating to families shape the lives of all people. This can have negative effects upon non-traditional families. This is especially the case in terms of adoption, where a focus solely on the adoptive family can often result in the ‘disappearance’ of the birth family. This paper explores the location of birth families in relation to adoptive families by examining a sample of children's storybooks aimed at adoptive children living with lesbian or gay parents as but one example of how policy makers may come to identify dominant cultural norms that circulate about birth families in the context of intercountry adoption. A number of key tropes are identified across these books, namely the ghostly presence of birth families, and the representation of birth parents as deviant (thus warranting the removal of their children).
Coastal wave reflection, directional spread, and seismoacoustic noise sources
Authors: Ardhuin Fabrice , Roland Aron
Published: May 2012

Coastal reflection is introduced in a phase‐averaged numerical wave model, first with a constant coefficient, and then with a reflection coefficient defined from the shoreface slope and that depends on the incident wave height and mean frequency. This parameterization is used in both regular and unstructured grids. The calibration involves a site‐specific shoreface slope that is associated with the local geomorphology of the shoreline. Using wave buoy data off Hawaii and the U.S. West Coast, it is found that coastal reflection is necessary to reproduce observed directional properties of coastal sea states. Errors on the mean directional spread are reduced by up to 30% for the frequency band 0.04 to 0.30 Hz with, at most locations, very little impact on the mean direction and energy levels. The most accurate results are obtained using the parameterization based on the shoreface slope, provided that this slope is estimated accurately. These parameterizations are validated using seismic noise data. Using data from the U.S. West Coast it is shown that the reflection defined from the shoreface slope can improve the correlation between measured and modeled seismic noise.
Why continuous simulation? The role of antecedent moisture in design flood estimation
Authors: Pathiraja S. , Westra S. , Sharma A.
Published: May 2012

Continuous simulation for design flood estimation is increasingly becoming a viable alternative to traditional event‐based methods. The advantage of continuous simulation approaches is that the catchment moisture state prior to the flood‐producing rainfall event is implicitly incorporated within the modeling framework, provided the model has been calibrated and validated to produce reasonable simulations. This contrasts with event‐based models in which both information about the expected sequence of rainfall and evaporation preceding the flood‐producing rainfall event, as well as catchment storage and infiltration properties, are commonly pooled together into a single set of “loss” parameters which require adjustment through the process of calibration. To identify the importance of accounting for antecedent moisture in flood modeling, this paper uses a continuous rainfall‐runoff model calibrated to 45 catchments in the Murray‐Darling Basin in Australia. Flood peaks derived using the historical daily rainfall record are compared with those derived using resampled daily rainfall, for which the sequencing of wet and dry days preceding the heavy rainfall event is removed. The analysis shows that there is a consistent underestimation of the design flood events when antecedent moisture is not properly simulated, which can be as much as 30% when only 1 or 2 days of antecedent rainfall are considered, compared to 5% when this is extended to 60 days of prior rainfall. These results show that, in general, it is necessary to consider both short‐term memory in rainfall associated with synoptic scale dependence, as well as longer‐term memory at seasonal or longer time scale variability in order to obtain accurate design flood estimates.
Real‐time, reliable magnitudes for large earthquakes from 1 Hz GPS precise point positioning: The 2011 Tohoku‐Oki (Japan) earthquake
Authors: Wright Tim J. , Houlié Nicolas , Hildyard Mark , Iwabuchi Tetsuya
Published: May 2012

The early warning issued after the onset of the Mw9.0 Tohoku‐Oki earthquake significantly underestimated its magnitude, saturating, 120 seconds after the earthquake began, at Mw8.1. Here we investigate whether real‐time deformation data from Japan's dense network of continuously‐recording Global Positioning System (GPS) stations could have been used to provide a more reliable rapid estimate of the earthquake's magnitude, and ultimately a more robust tsunami forecast. We use precise point positioning in real‐time mode with broadcast clock and orbital corrections to give station positions every 1 s. We then carry out a simple static inversion on a subset of stations to determine the portion of the fault that slipped and the earthquake magnitude. Unlike most previous methods, our method produces estimates of seismic moment before the earthquake rupture has completed. We find that the deformation data allow a robust magnitude estimate just ∼100 s after the earthquake onset. We also investigated the density of stations required for a robust moment magnitude estimate. Fewer than 1 station every 100 km are needed. We recommend that GPS data be incorporated into earthquake early warning systems for regions at threat from large magnitude earthquakes and tsunamis.
Does direct impact of SST on short wind waves matter for scatterometry?
Authors: Grodsky Semyon A. , Kudryavtsev Vladimir N. , Bentamy Abderrahim , Carton James A. , Chapron Bertrand
Published: May 2012

Scatterometer radar backscatter depends on the relationship linking surface stress and surface roughness. SST can alter the growth rate of centimeter‐scale waves through its impact on air and water density and water viscosity. This SST‐dependency hasnotbeen included in the standard Geophysical Model Functions. This study uses a radar imaging model to evaluate this SST‐dependence and compares the results to observations from QuikScat Ku‐band and ASCAT C‐band scatterometers. A SST correction could raise wind speeds by up to 0.2 ms−1in the storm track region of the Southern Ocean for C‐band scatterometers. For the higher frequency Ku‐band scatterometers, a SST‐induced reduction up to 0.4 ms−1 is predicted south of 60°S, where SST is cold and winds are moderate.
Thermosphere and ionosphere response to subauroral polarization streams (SAPS): Model simulations
Authors: Wang Wenbin , Talaat Elsayed R. , Burns Alan G. , Emery Barbary , Hsieh Syau‐yun , Lei Jiuhou , Xu Jiyao
Published: May 2012

An empirical model of subauroral polarization streams (SAPS) has been incorporated into the Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM). This SAPS driven TIEGCM is used to simulate the effect of SAPS on the global thermosphere and ionosphere during a moderate geomagnetically active period between day of year (DOY) 329 and 333 in 2008. Model results show: (1) SAPS caused an increase in global thermospheric temperature which became stronger with time. This neutral temperature increase was more significant in subauroral and auroral regions. Joule heating by the SAPS and the redistribution of this heat by dynamic processes were the primary mechanisms for the simulated global neutral temperature changes. (2) In the SAPS driven TIEGCM, the strong ion drag effect in the subauroral SAPS channel drove large changes in thermospheric winds. Zonal neutral winds had either an extra, separate channel of westward flow in the subauroral region in the afternoon‐midnight sector or a broad westward wind jet that merged with the regular duskside auroral westward zonal neutral wind driven by the high latitude convection pattern. The exact latitudinal profile of the zonal winds depended on local time. (3) The response of neutral temperature and wind to SAPS was more significant at higher altitudes and exhibited seasonal/hemispheric asymmetry. (4) The heating to the thermosphere by SAPS also resulted in changes in thermospheric composition with upwelling of molecular rich air in subauroral and auroral regions and downwelling of atomic oxygen rich air at other latitudes. These changes in thermospheric composition contributed to the deeper and more extended ionospheric electron density depletions in subauroral middle latitude regions, as well as electron density increases along the equatorward edge of the SAPS channel in the afternoon sector.
Measurements of OH and RO2 radicals at the coastal Antarctic site of Dumont d'Urville (East Antarctica) in summer 2010–2011
Authors: Kukui A. , Legrand M. , Ancellet G. , Gros V. , Bekki S. , Sarda‐Estève R. , Loisil R. , Preunkert S.
Published: May 2012

Measurements of OH and total peroxy RO2 (HO2 plus organic peroxy) radicals were conducted in December 2010/January 2011 at the coastal East Antarctic site of Dumont d'Urville (DDU, 66°40′S 140°01′E) as part of the Oxidant Production over Antarctic Land and its Export (OPALE) project. Compared to measurements carried out at the West Antarctic coast, relatively high concentrations of radicals were found with 24 h average values of 2.1 × 106 and 3.3 × 108 molecule cm−3 for OH and peroxy radicals, respectively. On the basis of the steady state calculations, the observed high concentration of peroxy radicals is in good agreement with the observed levels of O3 and HCHO representing via their photolysis the major primary radical sources. The observed OH levels at DDU could be explained only assuming some RO2 to OH conversion mechanism equivalent to the presence of NO in the range of 10 to 50 pptv. As neither NO nor halogen oxides were measured at DDU the mechanism of this recycling could not be explicitly identified. However, an examination of variability of radical levels as a function of the origin (oceanic versus continental) of sampled air masses suggests a more important OH production from RO2 recycling in continental air masses.
The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation
Authors: Rudenko Iakov N. , Kaganovich Alice , Hauser David N. , Beylina Aleksandra , Chia Ruth , Ding Jinhui , Maric Dragan , Jaffe Howard , Cookson Mark R.
Published: May 2012

Autosomal-dominant missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a common genetic cause of PD (Parkinson's disease). LRRK2 is a multidomain protein with kinase and GTPase activities. Dominant mutations are found in the domains that have these two enzyme activities, including the common G2019S mutation that increases kinase activity 2–3-fold. However, there is also a genetic variant in some populations, G2385R, that lies in a C-terminal WD40 domain of LRRK2 and acts as a risk factor for PD. In the present study we show that the G2385R mutation causes a partial loss of the kinase function of LRRK2 and deletion of the C-terminus completely abolishes kinase activity. This effect is strong enough to overcome the kinase-activating effects of the G2019S mutation in the kinase domain. Hsp90 (heat-shock protein of 90 kDa) has an increased affinity for the G2385R variant compared with WT (wild-type) LRRK2, and inhibition of the chaperone binding combined with proteasome inhibition leads to association of mutant LRRK2 with high molecular mass native fractions that probably represent proteasome degradation pathways. The loss-of-function of G2385R correlates with several cellular phenotypes that have been proposed to be kinase-dependent. These results suggest that the C-terminus of LRRK2 plays an important role in maintaining enzymatic function of the protein and that G2385R may be associated with PD in a way that is different from kinase-activating mutations. These results may be important in understanding the differing mechanism(s) by which mutations in LRRK2 act and may also have implications for therapeutic strategies for PD.
Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated pathway and utilizes the immunoproteasome subunit LMP2
Authors: Sun Haiyan , Lee Choon-myung , Tripathi Shweta , Kim Kyung-Bo , Morgan Edward T.
Published: May 2012

CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation, but the mechanisms and the reasons for the specificity towards only certain P450 (cytochrome P450) enzymes are yet unknown. In the present study we found that down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by pretreatment of the hepatocytes with IL-1 (interleukin-1β) in the presence of an NO synthase inhibitor, suggesting that an NO-independent action of IL-1 contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2 (large multifunctional peptidase 2) was significantly expressed in hepatocytes under basal conditions, and IL-1 induced LMP2 within 6–12 h of treatment. CYP2B protein degradation in response to IL-1 was attenuated by the selective LMP2 inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results show that LMP2 contributes to the NO-dependent degradation of CYP2B proteins, and suggest that induction of LMP2 may be involved in the potentiation of this degradation by IL-1.
TNF-related apoptosis-inducing ligand significantly attenuates metabolic abnormalities in high-fat-fed mice reducing adiposity and systemic inflammation
Authors: Bernardi Stella , Zauli Giorgio , Tikellis Christos , Candido Riccardo , Fabris Bruno , Secchiero Paola , Cooper Mark E. , Thomas Merlin C.
Published: May 2012

TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] has recently been shown to ameliorate the natural history of DM (diabetes mellitus). It has not been determined yet whether systemic TRAIL delivery would prevent the metabolic abnormalities due to an HFD [HF (high-fat) diet]. For this purpose, 27 male C57bl6 mice aged 8 weeks were randomly fed on a standard diet, HFD or HFD+TRAIL for 12 weeks. TRAIL was delivered weekly by intraperitoneal injection. Body composition was evaluated; indirect calorimetry studies, GTT (glucose tolerance test) and ITT (insulin tolerance test) were performed. Pro-inflammatory cytokines, together with adipose tissue gene expression and apoptosis, were measured. TRAIL treatment reduced significantly the increased adiposity associated with an HFD. Moreover, it reduced significantly hyperglycaemia and hyperinsulinaemia during a GTT and it improved significantly the peripheral response to insulin. TRAIL reversed the changes in substrate utilization induced by the HFD and ameliorated skeletal muscle non-esterified fatty acids oxidation rate. This was associated with a significant reduction of pro-inflammatory cytokines together with a modulation of adipose tissue gene expression and apoptosis. These findings shed light on the possible anti-adipogenic and anti-inflammatory effects of TRAIL and open new therapeutic possibilities against obesity, systemic inflammation and T2DM (Type 2 DM).
The Awareness of the Profession of Audiology Among Entering College Students
Authors: Emanuel Diana C. , Donai Jeremy J. , Araj Chris F.
Published: May 2012

Purpose

The purpose of this study was to develop and pilot test a survey of entering college students' awareness of the profession of audiology and to report the preliminary results of the survey.

Method

A survey was developed and administered in 2003 at the California University of Pennsylvania. A modified survey was administered in 2009. Survey questions asked students to identify what audiologists do and the education requirements to become an audiologist.

Results

Seventeen percent of the students self-reported that they knew what an audiologist did and were able to accurately describe the profession. Approximately 30% of the students learned about audiology from family/friends. Students reported selecting their major based on interest in a specific field and not on market-driven forces such as job opportunities and salary.

Conclusion

Future surveys should be conducted to confirm the extent of the lack of visibility of audiology as a profession and to serve as a metric for the efficacy of future marketing efforts in the profession.
Plasmodium falciparum
erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children
Authors: Lavstsen Thomas , Turner Louise , Saguti Fredy , Magistrado Pamela , Rask Thomas S. , Jespersen Jakob S. , Wang Christian W. , Berger Sanne S. , Baraka Vito , Marquard Andrea M. , Seguin-Orlando Andaine , Willerslev Eske , Gilbert M. Thomas P. , Lusingu John , Theander Thor G.
Published: May 2012

The clinical outcome of
Plasmodium falciparum
infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of
P. falciparum
infections is associated with the type of
P. falciparum
erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of infected erythrocytes to anchor these to the vascular lining. Although
var2csa
, the
var
gene encoding the PfEMP1 associated with placental malaria, was discovered in 2003, the identification of the
var
/PfEMP1 variants associated with severe malaria in children has remained elusive. To identify
var
/PfEMP1 variants associated with severe disease outcome, we compared
var
transcript levels in parasites from 88 children with severe malaria and 40 children admitted to the hospital with uncomplicated malaria. Transcript analysis was performed by RT-quantitative PCR using a set of 42 primer pairs amplifying
var
subtype-specific loci covering most
var
/PfEMP1 subtypes. In addition, we characterized the near-full-length sequence of the most prominently expressed
var
genes in three patients diagnosed with severe anemia and/or cerebral malaria. The combined analysis showed that severe malaria syndromes, including severe anemia and cerebral malaria, are associated with high transcript levels of PfEMP1 domain cassette 8-encoding
var
genes. Transcript levels of group A
var
genes, including genes encoding domain cassette 13, were also significantly higher in patients with severe syndromes compared with those with uncomplicated malaria. This study specifies the
var
/PfEMP1 types expressed in severe malaria in children, and thereby provides unique targets for future efforts to prevent and treat severe malaria infections.
A restricted subset ofvargenes mediates adherence ofPlasmodium falciparum-infected erythrocytes to brain endothelial cells
Authors: Avril Marion , Tripathi Abhai K. , Brazier Andrew J. , Andisi Cheryl , Janes Joel H. , Soma Vijaya L. , Sullivan David J. , Bull Peter C. , Stins Monique F. , Smith Joseph D.
Published: May 2012

Cerebral malaria (CM) is a deadly complication ofPlasmodium falciparuminfection, but specific interactions involved in cerebral homing of infected erythrocytes (IEs) are poorly understood. In this study,P. falciparum-IEs were characterized for binding to primary human brain microvascular endothelial cells (HBMECs). Before selection, CD36 or ICAM-1–binding parasites exhibited punctate binding to a subpopulation of HBMECs and binding was CD36 dependent. Panning of IEs on HBMECs led to a more dispersed binding phenotype and the selection of threevargenes, including two that encode the tandem domain cassette 8 (DC8) and were non-CD36 binders. Multiple domains in the DC8 cassette bound to brain endothelium and the cysteine-rich interdomain region 1 inhibited binding ofP. falciparum-IEs by 50%, highlighting a key role for the DC8 cassette in cerebral binding. It is mysterious how deadly binding variants are maintained in the parasite population. Clonal parasite lines expressing the two brain-adherent DC8-vargenes did not bind to any of the known microvascular receptors, indicating unique receptors are involved in cerebral binding. They could also adhere to brain, lung, dermis, and heart endothelial cells, suggesting cerebral binding variants may have alternative sequestration sites. Furthermore, young African children with CM or nonsevere control cases had antibodies to HBMEC-selected parasites, indicating they had been exposed to related variants during childhood infections. This analysis shows that specificP. falciparumerythrocyte membrane protein 1 types are linked to cerebral binding and suggests a potential mechanism by which individuals may build up immunity to severe disease, in the absence of CM.
Knockout of the prion protein (PrP)-like
Sprn
gene does not produce embryonic lethality in combination with PrP
C
-deficiency
Authors: Daude Nathalie , Wohlgemuth Serene , Brown Rebecca , Pitstick Rose , Gapeshina Hristina , Yang Jing , Carlson George A. , Westaway David
Published: May 2012

The
Sprn
gene encodes Shadoo (Sho), a glycoprotein with biochemical properties similar to the unstructured region of cellular prion protein (PrP
C
). Sho has been considered a candidate for the hypothetical π protein that supplies a PrP
C
-like function to maintain the viability of

Prnp
0/0

mice lacking the PrP
C
protein. To understand these relationships more clearly we probed the cell biology of Sho and created knockout mice. Besides full-length and a “C1” C-terminal fragment, we describe a 6-kDa N-terminal Sho neuropeptide, “N1,” which is present in membrane-enriched subcellular fractions of wild-type mice.
Sprn
null alleles were produced that delete all protein coding sequences yet spare the
Mtg
1 gene transcription unit that overlaps the
Sprn
3′ UTR; the resulting mice bred to homozygosity were viable and fertile, although

Sprn
0/0

mice maintained in two genetic backgrounds weighed less than wild-type mice. Lack of Sho protein did not affect prion incubation time. Contrasting with lethality reported for knockdown of expression in

Prnp
0/0

embryos using lentiviruses targeted against the
Sprn
3′ UTR, we established that double-knockout mice deficient in both Sho and PrP
C
are fertile and viable up to 690 d of age. Our data reduce the impetus for equating Sho with the notional π protein and are not readily reconciled with hypotheses wherein expression of PrP
C
and Sho are both required for completion of embryogenesis. Alternatively, and in accord with some reports for PrP
C
, we infer that Sho’s activity will prove germane to the maintenance of neuronal viability in postnatal life.
Functional roles of fructose
Authors: Kim Jinyoung , Song Gwonhwa , Wu Guoyao , Bazer Fuller W.
Published: May 2012

During the periimplantation period of pregnancy, pig blastocysts undergo morphological changes and differentiation requiring secretion and transport of nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although glucose is an energy source for proliferation and growth of mammalian cells, the role of fructose in uterine histotroph is unclear although it is the most abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows, sheep, and pigs). In this study, we used porcine trophectoderm cells to determine that fructose increased cell proliferation, as did glucose. Western blot analyses of porcine trophectoderm cell extracts revealed that fructose increased the abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within 30 min, and those levels remained elevated to 120 min. Phosphorylation of both RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1) and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response to fructose is mediated via GFPT1 activation and the hexosamine pathway. We further demonstrated that fructose stimulates the production of hyaluronic acid via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results demonstrate critical roles for fructose that are mediated via the hexosamine biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine trophectoderm cells, and synthesis of hyaluronic acid, a significant glycosaminoglycan in the pregnant uterus.
Spontaneous transmitter release is critical for the induction of long-term and intermediate-term facilitation inAplysia
Authors: Jin Iksung , Puthanveettil Sathya , Udo Hiroshi , Karl Kevin , Kandel Eric R. , Hawkins Robert D.
Published: May 2012

Long-term plasticity can differ from short-term in recruiting the growth of new synaptic connections, a process that requires the participation of both the presynaptic and postsynaptic components of the synapse. How does information about synaptic plasticity spread from its site of origin to recruit the other component? The answer to this question is not known in most systems. We have investigated the possible role of spontaneous transmitter release as such a transsynaptic signal. Until recently, relatively little has been known about the functions of spontaneous release. In this paper, we report that spontaneous release is critical for the induction of a learning-related form of synaptic plasticity, long-term facilitation inAplysia. In addition, we have found that this signaling is engaged quite early, during an intermediate-term stage that is the first stage to involve postsynaptic as well as presynaptic molecular mechanisms. In a companion paper, we show that spontaneous release from the presynaptic neuron acts as an orthograde signal to recruit the postsynaptic mechanisms of intermediate-term facilitation and initiates a cascade that can culminate in synaptic growth with additional stimulation during long-term facilitation. Spontaneous release could make a similar contribution to learning-related synaptic plasticity in mammals.
Emergence and equivocal autonomization of a Kurdish literary field in Turkey
Authors: Scalbert-Yücel Clémence
Published: May 2012

Drawing on field theory, this paper aims to shed light on the development and functioning of the Kurdish literary world in Turkey, characterized, in particular, by the use of a non-official language. It argues that this “small literary world” is to be understood in relation to a “double macrocosm”: the sphere of Kurdish politics and the national Turkish sphere, which provide specific constraints and resources. The paper argues that in such a context the emergence of a literary field, autonomous from other social fields and independent from political stakes, follows an unpredictable path, and will not always be achieved political dimension of the literary act stresses its dependency on political stakes and the field of politics. This however does not impede the emergence of autonomous literary institutions. The multilingualism of the actors involved drives also toward another heteronomy: this small literary world is also to be understood in relation to the Turkish literary field. The paper first presents the macrocosms in which Kurdish literary activities developed. It then examines the progressive integration of a field freeing itself from political constraints. Lastly, it focuses on the trajectories of a few writers, the analyses of which show the intertwining of the different worlds.
Monteverdi, Early Opera and a Question of Genre: The Case of Andromeda (1620)
Authors: Carter Tim
Published: May 2012

In 1985, Albi Rosenthal reported his discovery of a printed libretto for the opera Andromeda, composed by Monteverdi for performance in Mantua in Carnival 1620. This libretto deserves a new examination for its dramatic content, its likely musical setting (now lost) and some fundamental questions of genre. Its patron, Prince Vincenzo Gonzaga, used the librettist Hercole Marliani to broker his self-fashioning by imitating both Monteverdi's Orfeo (1607), supported by Vincenzo's elder brother, and Arianna (1608), which in effect belonged to the prince's parents. Monteverdi was typically slow to produce the score. The customary explanation is his disenchantment with Mantua and his new duties at St Mark's, Venice. However, we now see that both the Gonzagas and Monteverdi used Andromeda, like others of his Mantuan-commissioned works, as a bargaining chip in a complex exchange of obligations and favours typical of the courtly world to which the composer still belonged.
SALIGN: a web server for alignment of multiple protein sequences and structures
Authors: Braberg Hannes , Webb Benjamin M. , Tjioe Elina , Pieper Ursula , Sali Andrej , Madhusudhan M.S.
Published: May 2012

Summary: Accurate alignment of protein sequences and/or structures is crucial for many biological analyses, including functional annotation of proteins, classifying protein sequences into families, and comparative protein structure modeling. Described here is a web interface to SALIGN, the versatile protein multiple sequence/structure alignment module of MODELLER. The web server automatically determines the best alignment procedure based on the inputs, while allowing the user to override default parameter values. Multiple alignments are guided by a dendrogram computed from a matrix of all pairwise alignment scores. When aligning sequences to structures, SALIGN uses structural environment information to place gaps optimally. If two multiple sequence alignments of related proteins are input to the server, a profile–profile alignment is performed. All features of the server have been previously optimized for accuracy, especially in the contexts of comparative modeling and identification of interacting protein partners.

Availability: The SALIGN web server is freely accessible to the academic community at http://salilab.org/salign. SALIGN is a module of the MODELLER software, also freely available to academic users (http://salilab.org/modeller).

Contact:  sali@salilab.org; madhusudhan@bii.a-star.edu.sg
Effects of Brans from Specialty Sorghum Varieties on In Vitro Starch Digestibility of Soft and Hard Sorghum Endosperm Porridges
Authors: Austin Dilek Lemlioglu , Turner Nancy D. , McDonough Cassandra M. , Rooney Lloyd W.
Published: May 2012

Brans of specialty sorghum varieties (high tannin, black, and black with tannin) were used to investigate the effects of sorghum phenolic compounds on starch digestibility of soft and hard sorghum endosperm porridges. Endosperms of varieties with the highest and lowest grain hardness index were mixed with brans of specialty sorghum varieties in the ratio of 85:15 and cooked into porridges with distilled water using a Rapid Visco Analyzer. Brans of condensed tannin containing sorghum varieties (high‐tannin and black with tannin sorghums) significantly (P < 0.05) decreased starch digestibility and estimated glycemic index (EGI) and increased resistant starch (RS) content of endosperm porridges. However, the addition of phenolic‐rich tannin‐free (mostly anthocyanins) black sorghum bran significantly (P < 0.05) increased starch digestibility and EGI but did not affect RS content of endosperm porridges. The disparate effects with black bran may, in part, result from its larger particle size and different bran structure compared with other sorghum varieties evaluated. Thus, our study showed that not only presence of phenolic compounds in the brans but also structural differences of specialty sorghum brans can have significant effects on starch digestibility.