bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential proinflammatory responses induced by diesel exhaust particles with contrasting PAH and metal content
Authors: Totlandsdal Annike I. , Låg Marit , Lilleaas Edel , Cassee Flemming , Schwarze Per
Published: July 2013

Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been linked with cellular production and release of several types of mediators related to pulmonary inflammation. A key challenge is to identify the specific components, which may be responsible for these effects. The aim of this study was to compare the proinflammatory potential of two DEP‐samples with contrasting contents of polycyclic aromatic hydrocarbons (PAHs) and metals. The DEP‐samples were compared with respect to their ability to induce cytotoxicity, expression and release of proinflammatory mediators (IL‐6, IL‐8), activation of mitogen‐activated protein kinases (MAPKs) and expression of CYP1A1 and heme oxygenase‐1 (HO‐1) in human bronchial epithelial (BEAS‐2B) cells. In addition, dithiothreitol and ascorbic acid assays were performed in order to examine the oxidative potential of the PM samples. The DEP‐sample with the highest PAH and lowest metal content was more potent with respect to cytotoxicity and expression and release of proinflammatory mediators, CYP1A1 and HO‐1 expression and MAPK activation, than the DEP‐sample with lower PAH and higher metal content. The DEP‐sample with the highest PAH and lowest metal content also possessed a greater oxidative potential. The present results indicate that the content of organic components may be determinant for the proinflammatory effects of DEP. The findings underscore the importance of considering the chemical composition of particulate matter‐emissions, when evaluating the potential health impact and implementation of air pollution regulations. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 188–196, 2015.
The Relationship Between Trajectories of Family/Cultural Stressors and Depression and Suicidal Ideation Among Substance Using Mexican‐American Adults
Authors: Saint Onge Jarron M. , Cepeda Alice , Lee King Patricia A. , Valdez Avelardo
Published: July 2013

We used an intersectional minority stress perspective to examine the association between family/cultural stress and mental health among substance‐using Mexican‐Americans. Employing a unique longitudinal sample of 239 socioeconomically disadvantaged, non‐injecting heroin‐using Mexican‐Americans from San Antonio, Texas, we examined how culturally relevant stressors are related to depression and suicidal ideation. First, we identified depression and suicidal ideation prevalence rates for this disadvantaged sample. Second, we determined how cultural stress is experienced over time using stress trajectories. Third, we evaluated how family/cultural stressors and stress trajectories are related to depression and suicidal ideation outcomes. Results showed high rates of baseline depression (24 %) and suicidal ideation (30 %). We used latent class growth analysis to identify three primary stress trajectories (stable, high but decreasing, and increasing) over three time points during 1 year. We found that the increasing stressors trajectory was associated with higher rates of depression and suicidal ideation, and that stress trajectories had unique relationships with mental illness. We also showed that baseline stressors, sum stressors, and high but decreasing stressors maintained positive associations with mental illness after controlling for baseline depression. Our results highlight the importance of focusing on within‐group, culturally specific stressors and addressing both operant and cumulative stressors in the study of mental health for marginalized populations and suggest the importance of early intervention in minimizing stressors.
Effects of Fats and Oils on Rheological, Fatty Acid Profile and Quality Characteristics of South Indian Parotta
Authors: Tejaswi Kumar H. C. , Jeyarani T. , Milind  , Indrani D.
Published: July 2013

Keeping in view the present day demand for foods with healthy fats, the effect of different fats namely hydrogenated fat (HF) and bakery fat (BF); oils—sunflower oil (SFO), soyabean oil (SBO), olive oil (OLO), palm oil (POO) and coconut oil (CNO) separately at the level of 7.5 % on the rheological, fatty acid profile and quality characteristics of parotta was studied. Addition of fats and oils decreased Farinograph water absorption, Amylograph peak viscosity, Alveograph resistance of dough to deformation and increased average abscissa at rupture. In the micrographs of parotta dough with fats, the protein matrix appeared thick and intact, whereas in the case of parotta dough with oils the protein matrix appeared slightly less intact. The spread ratio and overall quality of parotta with oils were higher than fats. The highest overall quality score was observed for parotta with OLO, followed in decreasing order by SFO, SBO, CNO, POO, HF and BF. Determination of fatty acid profile showed that the parottas with fats contained a high amount of trans fatty acids (TFA), while parottas with oils had no TFA. During storage up to 48 h, the parottas with oils remained softer than the parottas with fats.
The Impact of Educational Homogamy on Isolated Illiteracy Levels
Authors: Permanyer Iñaki , García Joan , Esteve Albert
Published: July 2013

In this article, we explore the impacts that education expansion and increased levels in educational homogamy have had on couples’ isolated illiteracy rates, defined as the proportion of illiterates in union that are married to an illiterate partner. First, we develop the methodology to decompose isolated illiteracy rates into two main components: one related to level of homogamy among illiterates, and the other related to the educational distribution of the spouses. Second, we use harmonized international census microdata from IPUMS and DHS data for 73 countries and 217 samples to investigate which of the two components is more important in shaping the level of isolated illiteracy. Our results indicate that the expansion of literacy has been more powerful than the increases in the tendency toward homogamy in its impact on isolated illiteracy rates. As the percentage of illiterates decreases over time, an increasingly large proportion of them marry literate individuals, showing that opportunities for intermarriage among illiterates expand despite the strengthening of homogamy.
The V1/V2 loop of HIV‐1 gp120 is necessary for Tat binding and consequent modulation of virus entry
Authors: Cardaci Sabrina , Soster Marco , Bussolino Federico , Marchiò Serena
Published: July 2013

Preventing cell entry of human immunodeficiency virus 1 (HIV‐1) is of interest for the development of innovative therapies. We previously reported a specific interaction between HIV‐1 envelope glycoprotein 120 (gp120) and Tat at the cell surface, which enhances virus attachment and entry. We also identified a gp120‐mimicking peptide, CT319, that competes with gp120 for Tat binding, thus inhibiting HIV‐1 infection. Here we report a molecular dissection of gp120 regions involved in this mechanism. Our findings identify the V1/V2 loop of gp120 as involved in Tat binding, and define this interaction as functionally relevant for HIV‐1 entry into host cells.
The MFS‐type efflux pump Flr1 induced by Yap1 promotes canthin‐6‐one resistance in yeast
Authors: Dejos Camille , Régnacq Matthieu , Bernard Marianne , Voisin Pierre , Bergès Thierry
Published: July 2013

Screening for suppressors of canthin‐6‐one toxicity in yeast identified Yap1, a transcription factor involved in cell response to a broad range of injuries. Although canthin‐6‐one did not promote a significant oxidative stress, overexpression of YAP1 gene clearly increased resistance to this drug. We demonstrated that Yap1‐mediated resistance involves the plasma membrane major‐facilitator‐superfamily efflux pump Flr1 but not the vacuolar ATP‐binding‐cassette transporter Ycf1. FLR1 overexpression was sufficient to reduce sensitivity to the drug, but strictly dependent on a functional YAP1 gene.
Epitope‐based DNA vaccine for Alzheimer's disease: Translational study in macaques
Authors: Evans Claire F. , Davtyan Hayk , Petrushina Irina , Hovakimyan Armine , Davtyan Arpine , Hannaman Drew , Cribbs David H. , Agadjanyan Michael G. , Ghochikyan Anahit
Published: July 2013

Background

Clinical trials with passive and active Alzheimer's disease (AD) vaccines suggest that early interventions are needed for improvement of cognitive and/or functional performance in patients, providing impetus for the development of safe and immunologically potent active vaccines targeting amyloid β (Aβ). The AN‐1792 trial has indicated that Aβ‐specific T cells may be unsafe for humans; therefore, other vaccines based on small Aβ epitopes are undergoing preclinical and clinical testing.

Methods

Humoral and cellular immune responses elicited in response to a novel DNA epitope‐based vaccine (AV‐1955) delivered to rhesus macaques using the TriGrid electroporation device were evaluated. Functional activities of anti‐Aβ antibodies generated in response to vaccination were assessed in vitro.

Results

AV‐1955 generates long‐term, potent anti‐Aβ antibodies and cellular immune responses specific to foreign T‐helper epitopes but not to self‐Aβ.

Conclusions

This translational study demonstrates that a DNA‐based epitope vaccine for AD could be appropriate for human clinical testing.
Nonviolence in Our Abortion Discourse? A Postelection Opening
Authors: Camosy Charles
Published: July 2013

Some believe that there is no hope for moving beyond the culture wars in the United States—especially when they are connected to the persistently difficult abortion debate. This article argues, however, that the situation is more hopeful than most realize. The imagined “choice” and “life” camps do not map onto the complex reality of public opinion, especially among the Millennials. This article contends that “nonviolence” is an important common value for different kinds of people who imagine themselves to be on very different sides in the abortion debate. When applied consistently to rhetoric, individual persons and bodies, and social structures, a commitment to nonviolence not only provides an opening for productive and authentic discussion but also highlights broad areas of agreement and common ground.
I. Notes on Brachiopoda from the Pebble-bed of the Lower Greensand of Surrey; with Descriptions of the New Species, and Remarks on the Correlation of the Greensand Beds of Kent, Surrey, and Berks, and of the Farringdon Sponge-gravel and the Tourtia of Belgium
Authors: Meÿer C. J. A.
Published: July 2013

The pebble-bed of the Lower Greensand of Godalming has been already referred to (‘Geologist,’ vol. vi. pp. 53, 54) as a singular deposit, underlying the Bargate-stone series of that neighbourhood, remarkable alike on account of its peculiar organisms and its (probable) relation to other distant, though somewhat similar, beds; its position in the Greensand is fortunately well-marked, being immediately at the base of Fitton's ‘Upper or Ferruginous division;’ or, following the nomenclature of the Geological Survey, at the base of the ‘Folkestone Beds.’ in composition, it may be roughly described as a mixture of sand and small subangular pebbles, either loosely bedded or variously concreted. Its thickness at Godalming varies considerably, thinning out rapidly to the south of the town, but increasing on the north, in approaching the Hogsback, to a thickness of 8 or 10 feet; occasionally passing into, and alternating with, the lower layers of the Bargate-stone.
‘LET US RALLY AROUND THE FLAG’: FOOTBALL, NATION-BUILDING, AND PAN-AFRICANISM IN KWAME NKRUMAH'S GHANA
Authors: Darby Paul
Published: July 2013

The nationalistic fervour that greeted Ghana's performances in the 2010 football World Cup in South Africa powerfully evoked memories of an earlier period in the history of the Ghanaian state that witnessed Kwame Nkrumah, the first president of independent Ghana, draw on the game as a rallying point for nation-building and pan-African unity. This article uncovers this history by analysing Nkrumah's overt politicisation of football in the late colonial and immediate postcolonial periods. This study not only makes a novel contribution to the growing historical and social scientific literature on what is arguably Africa's most pervasive popular cultural form but also deepens our understanding of one of the continent's most significant political figures.
No Boundaries Here: Brecht, Lauwers, and European Theatre after Postmodernism
Authors: Freeman John
Published: July 2013

In this article John Freeman focuses on theatre after postmodernism as exemplified by the Belgium-based Needcompany. If, as is suggested here, we are all more than a little ‘postmoderned out’ through an over-dependence on individualism, the shadow cast by postmodernism remains large in the contemporary Western world, and its impact is still clearly felt. As the postmodern came to offer a safety net through which bad practice could not easily fall, the modernist theatre it followed offered its own elusive ideal. In arguing this, Freeman forges links between Brecht's knowing embrace of amateurism and the faux uncertainty of much contemporary work, where Brecht the arch-dramatist becomes the archetype of the postdramatic, as twenty-first century theatre moves in the shadow of the past. John Freeman has written extensively on contemporary performance, creative learning, and arts policy. He is currently Associate Professor at Curtin University, Western Australia, where he leads the Humanities Honours programme.
Introduction: Domestic Courts as Agents of Development of International Law
Authors: TZANAKOPOULOS ANTONIOS , TAMS CHRISTIAN J.
Published: July 2013

This introductory paper to the symposium hosted by theLeiden Journal of International Law, and edited by the authors, deals with the function of domestic courts as agents for the development of international law. The paper ‘sets the scene’ for the contributions to the symposium, which seek to trace the impact of domestic courts in the development of canonical areas of international law, such as jurisdiction, immunity, state responsibility, the law of international organizations/human rights, and the law of armed conflict/conduct of hostilities. It discusses the formal quality and actual influence of domestic-court decisions on the development of international-law, and introduces the concept of ‘agents’ of international-law development. This is the analytical perspective that the contributions to the symposium adopt.
Internationally Wrongful Acts in the Domestic Courts: The Contribution of Domestic Courts to the Development of Customary International Law Relating to the Engagement of International Responsibility
Authors: OLLESON SIMON
Published: July 2013

The rules of customary international law governing when a state or international organization will be held to have committed an internationally wrongful act, thereby engaging its international responsibility, are relatively well settled in international practice and jurisprudence. A key point of reference in this regard is the work of the International Law Commission on State Responsibility and Responsibility of International Organizations. The present paper examines relevant practice of domestic courts from a variety of jurisdictions which have relied upon the ILC's work, and discusses the extent to which domestic courts may make a contribution to the further development of the rules relating to engagement of responsibility. It concludes that, due to the operation of rules of, inter alia, immunity and non-justiciability, the principal instance in which domestic courts may actually apply the rules of international law is where it is the responsibility of the forum state which is in issue.
Role of Soluble Epoxide Hydrolase in Exacerbation of Stroke by Streptozotocin-Induced Type 1 Diabetes Mellitus
Authors: Jouihan Sari A , Zuloaga Kristen L , Zhang Wenri , Shangraw Robert E , Krasnow Stephanie M , Marks Daniel L , Alkayed Nabil J
Published: July 2013

Hyperglycemia worsens stroke, yet rigorous glycemic control does not improve neurologic outcome. An alternative is to target downstream molecular mediator(s) triggered by hyperglycemia but independent of prevailing glycemia. Soluble epoxide hydrolase (sEH) is a potential mediator of injury via its metabolism of neuroprotective epoxyeicosatrienoic acids (EETs). We tested whether hyperglycemia exacerbates cerebral injury by upregulating sEH and decreasing brain EET levels. Type 1 diabetes mellitus was modeled by streptozotocin (STZ;50 mg/kg per day intraperitoneally, 5 days) in male mice. At 4 weeks, STZ-treated and control mice underwent 45-minute middle cerebral artery occlusion (MCAO) with or without sEH blockade by trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB;1 mg/kg intraperitoneally daily for 6 days before MCAO). The STZ-treated mice had increased sEH mRNA expression in cerebral vessels and decreased EET concentrations in brain. There was no difference in cortical perfusion between groups. The STZ-treated mice sustained larger brain infarct than controls. Pretreatment with t-AUCB eliminated the difference in infarct size and EETs concentration between STZ-treated mice and controls, without altering glycemia. We conclude that type 1 diabetes mellitus upregulates sEH mRNA and decreases concentrations of neuroprotective EETs within the brain, leading to worse stroke outcome. The data indicate that sEH antagonism may be beneficial in the setting of hyperglycemic stroke.
Effect of chemically modified graphene oxide on the phase separation behaviour and properties of an epoxy/polyetherimide binary system
Authors: Yu Guijun , Wu Peiyi
Published: July 2013

Adding GO-MDA can (1) suppress the CRIPS behavior of and (2) toughen and strengthen the DGEBA/PEI binary system.
Manganese(iii) acetylacetonate initiated RAFT polymerizations: an alternative and versatile RAFT initiator
Authors: Zheng Zhigui , Wang Wenxiang , Zhou Yuan , Zhang Zhengbiao , Zhu Xiulin
Published: July 2013

Manganese(iii) acetylacetonate (Mn(acac)3) was demonstrated to be a versatile and superior RAFT initiator for different kinds of monomers, RAFT agents and noticeably, for a wide range of temperatures.
Measuring Phonological Awareness in Deaf and Hard-of-Hearing Children
Authors: Webb Mi-young L. , Lederberg Amy R.
Published: July 2013

Purpose

This study evaluated psychometric properties of 2 phonological awareness (PA) tests normed for hearing children when used with deaf and hard-of-hearing (DHH) children with functional hearing. It also provides an in-depth description of these children's PA.

Method

One hundred and eight DHH children (mean age = 63.3 months) with cochlear implants or hearing aids were assessed in the fall and spring of the school year. Sixty-three percent communicated only with spoken language; 37% communicated with both sign and speech. Examiners administered PA subtests from the Phonological Awareness Test—2 and the Test of Preschool Early Literacy, along with assessments of speech perception and early literacy.

Results

Item analyses indicated that both tests showed good psychometric properties (e.g., high item discriminations and internal consistencies). DHH children scored higher on subtests and items that measured words, rhymes, and syllables than those that assessed phonemes. Although subtest difficulty influenced the factor structure in the fall, spring PA was best characterized as a single factor. PA correlated concurrently and predictively with early literacy.

Conclusions

This study suggests that these 2 standardized tests are valid for use with DHH children with functional hearing. Although delayed, these children's PA was structurally similar to that of hearing children.
Three Treatments for Bilingual Children With Primary Language Impairment: Examining Cross-Linguistic and Cross-Domain Effects
Authors: Ebert Kerry Danahy , Kohnert Kathryn , Pham Giang , Rentmeester Disher Jill , Payesteh Bita
Published: July 2013

Purpose

This study examines the absolute and relative effects of 3 different treatment programs for school-age bilingual children with primary or specific language impairment (PLI). It serves to expand the evidence base on which service providers can base treatment decisions. It also explores hypothesized relations between languages and cognition in bilinguals with PLI.

Method

Fifty-nine school-age Spanish–English bilingual children with PLI were assigned to receive nonlinguistic cognitive processing, English, bilingual (Spanish–English), or deferred treatment. Participants in each of the 3 active treatments received treatment administered by nationally certified speech-language pathologists. Pre- and post-treatment assessments measured change in nonlinguistic cognitive processing, English, and Spanish skills, and analyses examined change within and across both treatment groups and skill domains.

Results

All active treatment groups made significant pre- to post-treatment improvement on multiple outcome measures. There were fewer significant changes in Spanish than in English across groups. Between-group comparisons indicate that the active treatment groups generally outperformed the deferred treatment control, reaching statistical significance for 2 tasks.

Conclusion

Results provide insight into cross-language transfer in bilingual children and advance understanding of the general PLI profile with respect to relationships between basic cognitive processing and higher level language skills.
Vocal Function and Upper Airway Thermoregulation in Five Different Environmental Conditions
Authors: Sandage Mary J. , Connor Nadine P. , Pascoe David D.
Published: July 2013

Purpose

Phonation threshold pressure and perceived phonatory effort were hypothesized to increase and upper airway temperature to decrease following exposure to cold and/or dry air. Greater changes were expected with mouth versus nose breathing.

Method

In a within-participant repeated measures design, 15 consented participants (7 men, 8 women) completed 20-min duration trials to allow for adequate thermal equilibration for both nose and mouth breathing in 5 different environments: 3 temperatures (°C) matched for relative humidity (% RH), cold (15 °C, 40% RH), thermally neutral (25 °C, 40% RH), and hot (35 °C, 40% RH); and 2 temperatures with variable relative humidity to match vapor pressure for the neutral environment (25 °C, 40% RH), cold (15 °C, 74% RH) and hot (35 °C, 23% RH). Following each equilibration trial, measures were taken in this order: upper airway temperature (transnasal thermistor probe), phonation threshold pressure, and perceived phonatory effort.

Results

Data were analyzed using repeated measures analysis of variance, and no significant differences were established.

Conclusions

The study hypotheses were not supported. Findings suggest that the upper airway is tightly regulated for temperature when challenged by a realistic range of temperature and relative humidity environments. This is the first study of its kind to include measurement of upper airway temperature in conjunction with measures of vocal function.
Making Gender Ma(R)King Place: Youthful British Pakistani Muslim Women's Narratives of Urban Space
Authors: Mohammad Robina
Published: July 2013

This paper draws on a case study of youthful British Pakistani Muslim women located in one of the largest Pakistani Muslim communities in the UK, in the city of Birmingham, to examine their narratives of urban space. These narratives illuminate the performance of gendered, Muslim, public spatialities, a term I use to refer to the spatial practices and personal geographies of the body and territory. I explore the ways in which the everyday life world that cuts across South Asian Muslim society and a public realm encoded with secular liberal democratic values configures the spatial ranges, practices, and personal geographies of youthful Pakistani Muslim women. I identify the ideological, material, and affective modalities through which these are given form at the intersection of place, ‘race’, gender, and religion. Finally, I illustrate the ways in which the dynamic multiethnic, multicultural milieu of Birmingham's ‘Little Pakistan’ localities offer youthful Pakistani Muslim women alternative repertoires for remaking the self, promoting cultural change and a greater sense of inclusiveness and belonging In doing so I foreground the fluidity and dynamic character of British South Asian Muslim cultures, contesting their representations as fixed and bounded
The Entrepreneurial Turn in the Context of a Central State: Evasive Planning Regulation for Ikea in Israel
Authors: Charney Igal
Published: July 2013

This paper considers how municipal entrepreneurialism takes advantage of gaps between state-level planning regulation and local planning capacities. Tensions between local and upper tier regulatory apparatuses are common in Israel, a state characterized by a top-down statutory planning system, where major planning and development issues are subject to the approval of the central state. Intensifying interurban competition for capital investment has stirred local authorities to evade unwanted planning ordinances and central-state supervision while speeding up planning procedures to enhance local development. Taking a highly publicized development, the second IKEA megastore in Israel, this paper examines the sidestepping tactics and the deliberate misinterpretation of land-use regulation as an entrepreneurial strategy and how it really works. This strategy is composed of two dimensions. First, it is based on local know-how concerning planning regulations and taking advantage of ineffective and outdated central-state control. Second, beyond municipal entrepreneurialism, it indicates the practical redrawing of city-state relations in the realm of urban planning. Within the arsenal of local authorities, which are heavily dependent on the central state, this becomes a powerful instrument to boost entrepreneurial agendas.
Assigning a Volcano Alert Level: Negotiating Uncertainty, Risk, and Complexity in Decision-Making Processes
Authors: Fearnley Carina J
Published: July 2013

A volcano alert level system (VALS) is used to communicate warning information from scientists to civil authorities managing volcanic hazards. This paper provides the first evaluation of how the decision-making process behind the assignation of an alert level, using forecasts of volcanic behaviour, operates in practice. Using interviews conducted from 2007 to 2009 at five USGS-managed (US Geological Survey) volcano observatories (Alaska, Cascades, Hawaii, Long Valley, and Yellowstone), two key findings are presented here. First, that observatory scientists encounter difficulties in interpreting scientific data, and in making decisions about what a volcano is doing, when dealing with complex volcanic processes. Second, the decision to move between alert levels is based upon a complex negotiation of perceived social and environmental risks. This research establishes that decision-making processes are problematic in the face of intrinsic uncertainties and risks, such that warning systems become complex and nonlinear. A consideration of different approaches to negotiating uncertainty and risk that are deliberative would, therefore, be beneficial in volcanic hazard management insofar as these suggest effective practices for decision-making processes in assigning an alert level.
Fragment Screening for the Modelling Community: SPR, ITC, and Crystallography
Authors: Dolezal Olan , Doughty Larissa , Hattarki Meghan K. , Fazio Vincent J. , Caradoc-Davies Tom T. , Newman Janet , Peat Thomas S.
Published: July 2013

The SAMPL (Statistical Assessment of the Modelling of Proteins and Ligands) challenge brought together experimentalists and modellers in an effort to improve our understanding of chemical and biochemical systems so better modelling tools can be developed. The most recent challenge, SAMPL3, held at Stanford University in August 2011, was an attempt to improve the methods used to predict how small fragment compounds bind to proteins, and the protein chosen for this test was bovine trypsin. Surface plasmon resonance was used to screen 500 compounds from a Maybridge fragment library and these compounds were subsequently used to soak crystals of trypsin and the best hits were also characterised by isothermal titration calorimetry. We present methods used for the surface plasmon resonance and the isothermal titration calorimetry experiments, as well as the results for these methods and those compounds that were found in the crystal structures.
Microsatellite-encoded domain in rodent Sry functions as a genetic capacitor to enable the rapid evolution of biological novelty
Authors: Chen Yen-Shan , Racca Joseph D. , Sequeira Paul W. , Phillips Nelson B. , Weiss Michael A.
Published: July 2013

Significance

Gene duplication is prominent among evolutionary pathways through which novel transcription factors and gene regulatory networks evolve. A model in mammals is provided by Sry, a Y-encoded Sox factor that initiates male development. We provide evidence that a CAG DNA microsatellite invasion into the
Sry
gene of a rodent superfamily enabled its rapid evolution. This unstable microsatellite encodes a variable length glutamine-rich repeat domain. Our results suggest that intragenic complementation between the glutamine-rich domain and canonical Sry motifs accelerated their divergence through repeat length–dependent biochemical linkages. Such novelty may underlie emergence of non–Sry-dependent mechanisms of male sex determination.
Acute myeloid leukemia does not deplete normal hematopoietic stem cells but induces cytopenias by impeding their differentiation
Authors: Miraki-Moud Farideh , Anjos-Afonso Fernando , Hodby Katharine A. , Griessinger Emmanuel , Rosignoli Guglielmo , Lillington Debra , Jia Li , Davies Jeff K. , Cavenagh Jamie , Smith Matthew , Oakervee Heather , Agrawal Samir , Gribben John G. , Bonnet Dominique , Taussig David C.
Published: July 2013

Acute myeloid leukemia (AML) induces bone marrow (BM) failure in patients, predisposing them to life-threatening infections and bleeding. The mechanism by which AML mediates this complication is unknown but one widely accepted explanation is that AML depletes the BM of hematopoietic stem cells (HSCs) through displacement. We sought to investigate how AML affects hematopoiesis by quantifying residual normal hematopoietic subpopulations in the BM of immunodeficient mice transplanted with human AML cells with a range of genetic lesions. The numbers of normal mouse HSCs were preserved whereas normal progenitors and other downstream hematopoietic cells were reduced following transplantation of primary AMLs, findings consistent with a differentiation block at the HSC–progenitor transition, rather than displacement. Once removed from the leukemic environment, residual normal hematopoietic cells differentiated normally and outcompeted steady-state hematopoietic cells, indicating that this effect is reversible. We confirmed the clinical significance of this by ex vivo analysis of normal hematopoietic subpopulations from BM of 16 patients with AML. This analysis demonstrated that the numbers of normal CD34
+
CD38
−
stem-progenitor cells were similar in the BM of AML patients and controls, whereas normal CD34
+
CD38
+
progenitors were reduced. Residual normal CD34
+
cells from patients with AML were enriched in long-term culture, initiating cells and repopulating cells compared with controls. In conclusion the data do not support the idea that BM failure in AML is due to HSC depletion. Rather, AML inhibits production of downstream hematopoietic cells by impeding differentiation at the HSC–progenitor transition.
Aurora B and Cdk1 mediate Wapl activation and release of acetylated cohesin from chromosomes by phosphorylating Sororin
Authors: Nishiyama Tomoko , Sykora Martina M. , Huis in ’t Veld Pim J. , Mechtler Karl , Peters Jan-Michael
Published: July 2013

Sister chromatid cohesion depends on Sororin, a protein that stabilizes acetylated cohesin complexes on DNA by antagonizing the cohesin release factor Wings-apart like protein (Wapl). Cohesion is essential for chromosome biorientation but has to be dissolved to enable sister chromatid separation. To achieve this, the majority of cohesin is removed from chromosome arms in prophase and prometaphase in a manner that depends on Wapl and phosphorylation of cohesin’s subunit stromal antigen 2 (SA2), whereas centromeric cohesin is cleaved in metaphase by the protease separase. Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. At centromeres, the cohesin protector shugoshin (Sgo1)-protein phosphatase 2A (PP2A) antagonizes Aurora B and Cdk1 partly by dephosphorylating Sororin and thus maintains cohesion until metaphase. We propose that the stepwise loss of cohesion between chromosome arms and centromeres is caused by local regulation of Wapl activity, which is controlled by the phosphorylation state of Sororin.
High thermoelectric performance by resonant dopant indium in nanostructured SnTe
Authors: Zhang Qian , Liao Bolin , Lan Yucheng , Lukas Kevin , Liu Weishu , Esfarjani Keivan , Opeil Cyril , Broido David , Chen Gang , Ren Zhifeng
Published: July 2013

From an environmental perspective, lead-free SnTe would be preferable for solid-state waste heat recovery if its thermoelectric figure-of-merit could be brought close to that of the lead-containing chalcogenides. In this work, we studied the thermoelectric properties of nanostructured SnTe with different dopants, and found indium-doped SnTe showed extraordinarily large Seebeck coefficients that cannot be explained properly by the conventional two-valence band model. We attributed this enhancement of Seebeck coefficients to resonant levels created by the indium impurities inside the valence band, supported by the first-principles simulations. This, together with the lower thermal conductivity resulting from the decreased grain size by ball milling and hot pressing, improved both the peak and average nondimensional figure-of-merit (
ZT
) significantly. A peak
ZT
of ∼1.1 was obtained in 0.25 atom % In-doped SnTe at about 873 K.
Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain
Authors: Ward Andrew B. , Szewczyk Paul , Grimard Vinciane , Lee Chang-Wook , Martinez Lorena , Doshi Rupak , Caya Alexandra , Villaluz Mark , Pardon Els , Cregger Cristina , Swartz Douglas J. , Falson Pierre Guy , Urbatsch Ina L. , Govaerts Cedric , Steyaert Jan , Chang Geoffrey
Published: July 2013

P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATP-Binding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse P-gp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.
Loss of function of cinnamyl alcohol dehydrogenase 1 leads to unconventional lignin and a temperature-sensitive growth defect in
Medicago truncatula
Authors: Zhao Qiao , Tobimatsu Yuki , Zhou Rui , Pattathil Sivakumar , Gallego-Giraldo Lina , Fu Chunxiang , Jackson Lisa A. , Hahn Michael G. , Kim Hoon , Chen Fang , Ralph John , Dixon Richard A.
Published: July 2013

There is considerable debate over the capacity of the cell wall polymer lignin to incorporate unnatural monomer units. We have identified
Tnt1
retrotransposon insertion mutants of barrel medic (
Medicago truncatula
) that show reduced lignin autofluorescence under UV microscopy and red coloration in interfascicular fibers. The phenotype is caused by insertion of retrotransposons into a gene annotated as encoding cinnamyl alcohol dehydrogenase, here designated
M. truncatula CAD1
. NMR analysis indicated that the lignin is derived almost exclusively from coniferaldehyde and sinapaldehyde and is therefore strikingly different from classical lignins, which are derived mainly from coniferyl and sinapyl alcohols. Despite such a major alteration in lignin structure, the plants appear normal under standard conditions in the greenhouse or growth chamber. However, the plants are dwarfed when grown at 30 °C. Glycome profiling revealed an increased extractability of some xylan and pectin epitopes from the cell walls of the
cad1-1
mutant but decreased extractability of others, suggesting that aldehyde-dominant lignin significantly alters cell wall structure.
The Safety of SLICE (0.2% Emamectin Benzoate) Administered in Feed to Fingerling Rainbow Trout
Authors: Bowker James D , Carty Dan , Bowman Molly P
Published: July 2013

SLICE (0.2% emamectin benzoate [EB]) is an in-feed treatment that has been shown to be effective and safe for controlling infestations of several ectoparasitic crustacean copepods and branchiurans in a variety of seawater- and freshwater-reared fishes. Although the safety of EB (in a pre-SLICE formulation) for use with seawater-reared Rainbow Trout Oncorhynchus mykiss has been demonstrated, the safety of SLICE for freshwater-reared Rainbow Trout has not. Consequently, we conducted a trial to evaluate the safety of SLICE for freshwater-reared Rainbow Trout when administered in feed at a dose of 0 (0×), 50 (1 × the maximum proposed therapeutic dose [1×]), 100 (2×), or 150 (3×) μg of EB·kg of fish body weight (BW)−1·d−1 for 14 d (2 × the proposed 7-d treatment duration). Medicated feed was prepared by top-coating commercially available feed with SLICE. Rainbow Trout fingerlings (mean TL ± SD = 7.4 ± 0.7 cm; mean weight ± SD = 4.4 ± 1.2 g) were stocked into 57-L flow-through tanks at 20 fish/tank. Diets were randomly assigned to four replicate tanks per treatment; fish in four additional, nontrial tanks were fed control diets and were weighed weekly to calculate the proper feeding quantities. Throughout the trial, water quality was maintained within ranges suitable for Rainbow Trout culture, fish were fed the assigned feeds at 4% BW/d divided equally between three feedings, and fish behavior was characterized as normal. Fish in the 0×, 1×, and 2× exposure groups consumed all of the offered feed at least 92% of the time, whereas fish in the 3× exposure group consumed all of the offered feed 75% of the time. No fish died, and gross and microscopic fish health evaluations revealed no chronic toxicity patterns. Based on these results, we conclude that there is an adequate margin of safety associated with administering SLICE-medicated feed to fingerling Rainbow Trout at the proposed therapeutic treatment regimen of 50 μg EB·kg fish BW−1·d−1 for 7 d.
Automated Measures of Hand Hygiene Compliance among Healthcare Workers Using Ultrasound: Validation and a Randomized Controlled Trial
Authors: Fisher Dale A. , Seetoh Theresa , May-Lin Helen Oh , Viswanathan Sivakumar , Toh Yanling , Yin Wong Chiang , Eng Loh Siw , Yang Tan Shire , Schiefen Steve , Je Minkyu , Peh Ruey Feng , Loke Fiona Wei Ling , Dempsey Michael
Published: July 2013

Objective.

The primary objective of this study was to validate a novel method of assessing hand hygiene compliance using ultrasound transmitters in patient zones and staff tagged with receivers. The secondary objective was to assess the impact of audio reminders and quantified individual feedback.

Design.

An observational comparison against manual assessment followed by assessment using an open-label randomized control method.

Setting.

Patient zones were established in 3 wards of 2 large teaching hospitals, including 88 general and 18 intensive care unit ward beds.

Participants.

Consented regular ward nursing, medical, and allied health staff.

Methods.

Concordance between 40 hours of manual observation using trained hand hygiene auditors and automated measures of opportunities and compliance. Subsequent measured interventions were reminder beeps and written individual feedback.

Results.

When compared with manual observations, ultrasound monitoring underestimated percentage compliances by a nonsignificant mean (95% confidence interval [CI]) difference of 5.2% (−20.1% to 9.8%; P = .491). After the intervention, adjusted multivariate analysis showed mean (95% CI) overall compliance in the intervention arm was 6.8% (2.5%−11.1%; P = .002) higher than in the control arm. Results stratified by compliance at entry and exit showed that the effect of intervention was stronger for compliance at exit than at entry.

Conclusions.

Our automated measure of hand hygiene compliance is valid when compared with the traditional gold standard of manual observations. As an interventional tool, ultrasound-based automated hand hygiene audits have significant benefit that can be built upon with enhancements and find increasing acceptance with time.
Local computation of differents and discriminants
Authors: Nart Enric
Published: July 2013

We obtain several results on the computation of different and discriminant ideals of finite extensions of local fields. As an application, we deduce routines to compute the

p

\mathfrak {p}

-adic valuation of the discriminant

Disc
⁡
(
f
)

\operatorname {Disc}(f)

, and the resultant

Res
⁡
(
f
,
g
)

\operatorname {Res}(f,g)

, for polynomials

f
(
x
)
,
g
(
x
)
∈
A
[
x
]

f(x),g(x)\in A[x]

, where

A
A

is a Dedekind domain and

p

\mathfrak {p}

is a non-zero prime ideal of

A
A

with finite residue field. These routines do not require the computation of either

Disc
⁡
(
f
)

\operatorname {Disc} (f)

or

Res
⁡
(
f
,
g
)

\operatorname {Res}(f,g)

; hence, they are useful in cases where this latter computation is inefficient because the polynomials have a large degree or very large coefficients.
Circulating angiopoietin‐2, its soluble receptor Tie‐2, and mortality in the general population
Authors: Lorbeer Roberto , Baumeister Sebastian E. , Dörr Marcus , Nauck Matthias , Grotevendt Anne , Völzke Henry , Vasan Ramachandran S. , Wallaschofski Henri , Lieb Wolfgang
Published: July 2013

Aims

To assess the association of circulating concentrations of angiopoietin‐2 (Ang‐2) and its soluble receptor Tie‐2 (sTie‐2) with all‐cause, cardiovascular, and cancer mortality in a population‐based sample.

Methods and results

Angiopoietin‐2 and sTie‐2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow‐up of 6.2 years, 217 participants died. Ang‐2 levels were positively associated with all‐cause mortality [HR 1.29; 95% confidence interval (CI) 1.19–1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18–1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89–1.32; P = 0.416). Levels of sTie‐2 were not significantly related to all‐cause mortality (HR 1.12; 95% CI 0.98–1.27; P = 0.102). Adding Ang‐2 to a prediction model for all‐cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, −0.015; P = 0.571).

Conclusion

In our community‐based sample, higher serum Ang‐2 concentrations were associated with greater risk for all‐cause and cardiovascular mortality, suggesting that subtle increases in Ang‐2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang‐2 to a mortality prediction model only modestly improved discrimination.
N‐terminal pro brain natriuretic peptide but not copeptin improves prediction of heart failure over other routine clinical risk parameters in older men with and without cardiovascular disease: population‐based study
Authors: Goya Wannamethee S. , Welsh Paul , Whincup Peter H. , Lennon Lucy , Papacosta Olia , Sattar Naveed
Published: July 2013

Aims

Measurement of NT‐proBNP and copeptin may help identify those at high risk of heart failure (HF). However the value of NT‐proBNP and copeptin has been little studied in the older population in primary care. This study aims to examine the use of NT‐proBNP and copeptin in improving risk prediction and stratification of HF in older men with and without cardiovascular disease (CVD).

Methods and results

This was a prospective study of 3870 men aged 60–79 years with no diagnosed HF followed up for a mean period of 11 years, during which there were 254 incident HF cases. NT‐proBNP was associated with HF in those with and without established CVD [diagnosed myocardial infarction (MI), angina, or stroke]. NT‐proBNP improved prediction beyond routine conventional risk factors (age, obesity, diabetes, hypertension, history of MI, and history of angina) and the Health ABC Heart Failure Score in all men and in men with and without established CVD (P<0.0001 for improvement in c‐statistics). The net reclassification index (NRI) beyond conventional risk factors was 18.8% overall (27.4% for men without CVD and 17.4% for men with CVD). In contrast, copeptin was associated with HF in men with CVD only and did not improve prediction of HF after inclusion of conventional risk factors (P = 0.95 for improvement in c‐statistics).

Conclusion

NT‐proBNP, but not copeptin significantly improves prediction and risk stratification of HF beyond routine clinical parameters obtained in general practice settings in older men both with and without established CVD.
Epicurean Cannibalism, or France Gone Savage
Authors: Duggan Anne E.
Published: July 2013

This article explores the figure of the Epicurean-as-cannibal in the
Doctrine curieuse des beaux esprits de ce temps, ou pretendus tels
(1623) by the French Jesuit priest François Garasse. The
Doctrine
was drafted as an attack on the poet Théophile de Viau and his ‘Epicurean’ entourage, and was instrumental in transforming the French literary field of the early seventeenth century. Garasse uses the figure of the cannibal to locate Epicureans outside the civilized, Catholic, and human community. Cannibalism comes to signify transgressive, animal-like behaviour based on immanent desire as opposed to civilized behaviour guided by external law, while the cannibal serves as a figure for the heretical body that threatens to devour French youth. After comparing Théophile and Epicureans to cannibalistic peoples, Garasse moves on to associate them with cannibalistic animals in order to depict the supposed danger they represented to the Christian French body politic.