bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood in a digital age: creative challenges for educational futures
Authors: Craft Anna
Published: June 2012

The early twenty-first century is characterised by rapid change. Commentators note how permeating digital technologies engage increasing numbers of children, young people and adults as consumers and also producers. In the shifting technological landscape, childhood and youth are changing.
Connectivity around the clock, with a parallel existence in virtual space, is seamlessly integrated with actual lives. Young people are skilful collaborators, navigating digital gaming and social networking with ease, capably generating and manipulating content, experimenting virtually with
versions of their 'social face'. They are implicit, inherent and immersed consumers. They are digital possibility thinkers posing 'what if?' questions and engaging in 'as if' activity. This paper seeks to theorise such possibility thinking in a digital, marketised age, using two competing
discourses: young people as vulnerable and at risk; or alternatively as capable and potent. The former perspective imbues anxiety about the digital revolution; the latter embraces it as exciting and enabling. As education providers seek to re-imagine themselves, neither is sufficient. Local
and global challenges urgently demand our creative potential and wisdom. Drawing from work with schools, the paper argues for co-creating with students their education futures through dialogue to nurture the 4 Ps: plurality, playfulness, participation and possibilities.
Leadership and creativity in higher education: the role of interdisciplinarity
Authors: Kandiko Camille B.
Published: June 2012

Many organisations are under increasing pressures to recruit and retain creative individuals as a core asset in the emerging knowledge economy. In universities, such people are often academics who focus on high impact, innovative and interdisciplinary research. Yet, instead of feeling
supported, many of these academics face structural, epistemological and socio-cultural challenges. This paper reviews the role of creativity across disciplines in higher education and draws on interviews of 10 senior interdisciplinary leaders from the UK and Australia to discuss motivational
aspects of creativity, challenges of pursuing creative work and how creativity through interdisciplinarity can be supported in higher education. Leadership styles based on the various conceptions of creativity are proposed and further research is discussed.
Creative reflections on brainstorming
Authors: Byron Kevin
Published: June 2012

Brainstorming is the default method of idea-generation in organisations, and is widely applied in higher education by students, academics and support staff. Its popularity is mainly attributable to an illusory belief that groups working together are more productive than individuals
working apart. Shared responsibility, the need for collaboration and the social dimension to work also sustains the popularity of brainstorming. To add further insight to the numerous studies that have been demonstrated the inefficiencies of brainstorming, this paper describes preliminary
results on participants' self-reflection during a brainstorm. Recommendations are made for improving the productivity of group brainstorms.
Silences and silence in 'creativity'
Authors: Saunders Lesley
Published: June 2012

This reflective piece – written primarily to provoke discussion – raises some questions about and for the recent 'creativity agenda' in educational policy in England, suggesting that something fundamental is missing. The author argues that 'creativity' has characteristically
been defined in recent policy discourse as a set of skills concerned with developing independent thinking, problem-solving and flexible working. 'Creativity' thus turns out to be intimately and explicitly allied to 'employability'. The author believes that creativity, on the contrary, is stimulated
by the encouragement of vivid inner lifeworlds, a sense of imaginative interiority and a sensuously-felt subjectivity – as exemplified in S.T. Coleridge's poem Kubla Khan. She argues that these are part of pedagogic responsibility as well as a sine qua non for the work of the imagination.
The author is writing in her role as poet (who also leads creative writing workshops, including for teachers), rather than as a researcher.
Janus-like opposing roles of CD47 in autoimmune brain inflammation in
humans and mice
Authors: Han May H. , Lundgren Deborah H. , Jaiswal Siddhartha , Chao Mark , Graham Kareem L. , Garris Christopher S. , Axtell Robert C. , Ho Peggy P. , Lock Christopher B. , Woodard Joslyn I. , Brownell Sara E. , Zoudilova Maria , Hunt Jack F.V. , Baranzini Sergio E. , Butcher Eugene C. , Raine Cedric S. , Sobel Raymond A. , Han David K. , Weissman Irving , Steinman Lawrence
Published: June 2012

Comparison of transcriptomic and proteomic data from pathologically similar multiple sclerosis (MS) lesions reveals down-regulation of CD47 at the messenger RNA level and low abundance at the protein level. Immunohistochemical studies demonstrate that CD47 is expressed in normal myelin and in foamy macrophages and reactive astrocytes within active MS lesions. We demonstrate that CD47−/− mice are refractory to experimental autoimmune encephalomyelitis (EAE), primarily as the result of failure of immune cell activation after immunization with myelin antigen. In contrast, blocking with a monoclonal antibody against CD47 in mice at the peak of paralysis worsens EAE severity and enhances immune activation in the peripheral immune system. In vitro assays demonstrate that blocking CD47 also promotes phagocytosis of myelin and that this effect is dependent on signal regulatory protein α (SIRP-α). Immune regulation and phagocytosis are mechanisms for CD47 signaling in autoimmune neuroinflammation. Depending on the cell type, location, and disease stage, CD47 has Janus-like roles, with opposing effects on EAE pathogenesis.
Identification of broadly protective human antibodies toPseudomonas aeruginosaexopolysaccharide Psl by phenotypic screening
Authors: DiGiandomenico Antonio , Warrener Paul , Hamilton Melissa , Guillard Sandrine , Ravn Peter , Minter Ralph , Camara Maria Margarita , Venkatraman Vignesh , MacGill Randall S. , Lin Jia , Wang Qun , Keller Ashley Elaine , Bonnell Jessica C. , Tomich Mladen , Jermutus Lutz , McCarthy Michael P. , Melnick David A. , Suzich JoAnn A. , Stover C. Kendall
Published: June 2012

Pseudomonas aeruginosa is a leading cause of hospital-associated infections in the seriously ill, and the primary agent of chronic lung infections in cystic fibrosis patients. A major obstacle to effective control of P. aeruginosa infections is its intrinsic resistance to most antibiotic classes, which results from chromosomally encoded drug-efflux systems and multiple acquired resistance mechanisms selected by years of aggressive antibiotic therapy. These factors demand new strategies and drugs to prevent and treat P. aeruginosa infections. Herein, we describe a monoclonal antibody (mAb) selection strategy on whole P. aeruginosa cells using single-chain variable fragment phage libraries derived from healthy individuals and patients convalescing from P. aeruginosa infections. This approach enabled identification of mAbs that bind three distinct epitopes on the product of the Psl. This exopolysaccharide is important for P. aeruginosa attachment to mammalian cells, and for the formation and maintenance of biofilms produced by nonmucoid and mucoid P. aeruginosa isolates. Functional screens revealed that mAbs to one epitope exhibit superior activity in opsonophagocytic killing and cell attachment assays, and confer significant protection in multiple animal models. Our results indicate that Psl is an accessible serotype-independent surface feature and promising novel protective antigen for preventing P. aeruginosa infections. Furthermore, our mAb discovery strategy holds promise for application to other bacterial pathogens.
Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation
Authors: Boulard Olivier , Kirchberger Stefanie , Royston Daniel J. , Maloy Kevin J. , Powrie Fiona M.
Published: June 2012

Chronic inflammation of the intestine has been associated with an elevated risk of developing colorectal cancer. Recent association studies have highlighted the role of genetic predisposition in the etiology of colitis and started to unravel its complexity. However, the genetic factors influencing the progression from colon inflammation to tumorigenesis are not known. We report the identification of a genetic interval Hiccs that regulates Helicobacter hepaticus–induced colitis and associated cancer susceptibility in a 129.RAG−/− mouse model. The 1.7-Mb congenic interval on chromosome 3, containing eight genes and five microRNAs, renders susceptible mice resistant to colitis and reduces tumor incidence and multiplicity. Bone marrow chimera experiments showed that resistance is conferred by the hematopoietic compartment. Moreover, the Hiccs locus controls the induction of the innate inflammatory response by regulating cytokine expression and granulocyte recruitment by Thy1+ innate lymphoid cells. Using a tumor-promoting model combining chronic Helicobacter hepaticus infection and the carcinogen azoxymethane, we found that Hiccs also regulates the frequency of colitis-associated neoplasia. Our study highlights the importance of innate immune cells and their genetic configuration in driving progression from inflammation toward cancer and opens the door for analysis of these pathways in human inflammatory disorders and associated cancers.
ON THE SPECTRAL SHAPE OF RADIATION DUE TO INVERSE COMPTON SCATTERING CLOSE TO THE MAXIMUM CUTOFF
Authors: Lefa E. , Kelner S. R. , Aharonian F. A.
Published: June 2012

The spectral shape of radiation due to inverse Compton scattering is analyzed in the Thomson and the Klein–Nishina regime for electron distributions with exponential cutoff. We derive analytical, asymptotic expressions for the spectrum close to the maximum cutoff region. We consider monoenergetic, Planckian, and synchrotron photons as target photon fields. These approximations provide a direct link between the distribution of parent electrons and the upscattered spectrum at the cutoff region.
Improved memory behaviour of single-walled carbon nanotubes charge storage nodes
Authors: Alba-Martin Maria , Firmager Timothy , Atherton Joseph , Rosamond Mark C , Ashall Daniel , Ghaferi Amal Al , Ayesh Ahmad , Gallant Andrew J , Mabrook Mohammed F , Petty Michael C , Zeze Dagou A
Published: July 2012

To investigate their memory behaviours, single-walled carbon nanotubes (SWCNTs) were embedded in the floating gate of a hybrid metal–insulator–semiconductor structure using layer-by-layer deposition, and polymethylmethacrylate (PMMA) as the dielectric. Unlike longer SWCNT-based structures, shortened SWCNTs were shown to exhibit reliable and large memory windows by virtue of a better encapsulation which reduces charge leakage. The capacitance–voltage characteristics of the devices were consistent with electron injection into the SWCNT charge storage elements (in the floating) from the top electrode through the PMMA, using localized defects and crossing the PMMA energy barrier. In terms of material formulation, a combination of SWCNTs dispersed in sodium dodecyl sulfate and polyethyleneimine used as charge storage elements in the floating gate was shown to lead to repeatable and reliable memory characteristics. Fast switching and very large memory windows (∼7 V) exhibiting high charge density (2.6 × 1012 cm−2) and charge retention in excess of ∼76% were achieved under a ±10 V sweep voltage range. These results suggest that SWCNTs could lead to improved memory behaviour with the potential for application in plastic electronics.
Projective isomonodromy and Galois groups
Authors: Mitschi Claude , Singer Michael
Published: June 2012

In this article we introduce the notion of projective isomonodromy, which is a special type of monodromy-evolving deformation of linear differential equations, based on the example of the Darboux-Halphen equation. We give an algebraic condition for a parameterized linear differential equation to be projectively isomonodromic, in terms of the derived group of its parameterized Picard-Vessiot group.
Upper bounds for the number of number fields with alternating Galois group
Authors: Larson Eric , Rolen Larry
Published: June 2012

Let

N
(
n
,

A
n

,
X
)

N(n, A_n, X)

be the number of number fields of degree

n
n

whose Galois closure has Galois group

A
n

A_n

and whose discriminant is bounded by

X
X

. By a conjecture of Malle, we expect that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper N left-parenthesis n comma upper A Subscript n Baseline comma upper X right-parenthesis tilde upper C Subscript n Baseline dot upper X Superscript one half Baseline dot left-parenthesis log upper X right-parenthesis Superscript b Super Subscript n">

N
(
n
,

A
n

,
X
)
∼

C
n

⋅

X

1
2

⋅
(
log
⁡
X

)

b
n

N(n, A_n, X)\sim C_n\cdot X^{\frac {1}{2}} \cdot (\log X)^{b_n}

for constants

b
n

b_n

and

C
n

C_n

. For

6
≤
n
≤
84393

6 \leq n \leq 84393

, the best known upper bound is

N
(
n
,

A
n

,
X
)
≪

X

n
+
2

4

N(n, A_n, X) \ll X^{\frac {n + 2}{4}}

, by Schmidt’s theorem, which implies there are

≪

X

n
+
2

4

\ll X^{\frac {n + 2}{4}}

number fields of degree

n
n

. (For

n
>
84393

n > 84393

, there are better bounds due to Ellenberg and Venkatesh.) We show, using the important work of Pila on counting integral points on curves, that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper N left-parenthesis n comma upper A Subscript n Baseline comma upper X right-parenthesis much-less-than upper X Superscript StartFraction n squared minus 2 Over 4 left-parenthesis n minus 1 right-parenthesis EndFraction plus epsilon">

N
(
n
,

A
n

,
X
)
≪

X

n
2

−
2

4
(
n
−
1
)

+
ϵ

N(n, A_n, X) \ll X^{\frac {n^2 - 2}{4(n - 1)}+\epsilon }

, thereby improving the best previous exponent by approximately

1
4

\frac {1}{4}

for

6
≤
n
≤
84393

6 \leq n \leq 84393

.
CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome
Authors: Stern Adi , Mick Eran , Tirosh Itay , Sagy Or , Sorek Rotem
Published: June 2012

The bacterial community in the human gut has crucial health roles both in metabolic functions and in protection against pathogens. Phages, which are known to significantly affect microbial community composition in many ecological niches, have the potential to impact the gut microbiota, yet thorough characterization of this relationship remains elusive. We have reconstructed the content of the CRISPR bacterial immune system in the human gut microbiomes of 124 European individuals and used it to identify a catalog of 991 phages targeted by CRISPR across all individuals. Our results show that 78% of these phages are shared among two or more individuals. Moreover, a significant fraction of phages found in our study are shown to exist in fecal samples previously derived from American and Japanese individuals, identifying a common reservoir of phages frequently associated with the human gut microbiome. We further inferred the bacterial hosts for more than 130 such phages, enabling a detailed analysis of phage–bacteria interactions across the 124 individuals by correlating patterns of phage abundance with bacterial abundance and resistance. A subset of phages demonstrated preferred association with host genomes as lysogenized prophages, with highly increased abundance in specific individuals. Overall, our results imply that phage–bacterial attack–resistance interactions occur within the human gut microbiome, possibly affecting microbiota composition and human health. Our finding of global sharing of gut phages is surprising in light of the extreme genetic diversity of phages found in other ecological niches.
Dimerizer-Mediated Regulation of Gene Expression In Vivo
Authors: Rivera Victor M. , Berk Lori , Clackson Tim
Published: July 2012

Several systems have been developed that allow transcription of a target gene to be chemically controlled, usually by an allosteric modulator of transcription factor activity. An alternative is to use chemical inducers of dimerization, or “dimerizers,” to reconstitute active transcription factors from inactive fusion proteins. The most widely used system employs the natural product rapamycin, or a biologically inert analog, as the dimerizing drug. A key feature of this system is the tightness of regulation, with basal expression usually undetectable and induced expression levels comparable to constitutive promoters. In our experiments, the use of the minimal interleukin-2 (IL-2) promoter is an important determinant of this; substitution of a minimal simian virus 40 (SV40) or cytomegalovirus (CMV) promoter results in significantly higher levels of basal expression. The key factor dictating the successful use of the system is achieving high expression levels of the activation domain fusion protein. In the context of clinical gene therapies, the system has the advantage of being built exclusively from human proteins, potentially minimizing immunogenicity in the clinical setting. The dimerizer system has been successfully incorporated into diverse vector backgrounds and has been used to achieve long-term regulated gene expression in vitro and in vivo. This protocol describes how to achieve rapamycin- or rapalog-inducible gene expression in vivo.
Involving Young Disabled People in the Research Process: The Experiences of the PIE Research Project Team
Authors: Watson Debby , Feiler Anthony , Tarleton Beth
Published: June 2012

Young disabled people are still rarely involved in the research process, despite an increasing emphasis on their inclusion as participants. The Participation in Education (PIE) project examined how disabled children with little or no speech could be involved in their education. The project team worked with an existing group of young disabled people to develop ways in which they could take part in the research process. The group was involved in developing the methodology, group work, observation, commenting on findings and in the dissemination process. Their involvement undoubtedly enriched the research and the benefits of working with an established group were manifold.
Review article: non‐alcoholic fatty liver disease and osteoporosis – clinical and molecular crosstalk
Authors: Yilmaz Y.
Published: June 2012

Background

Low bone mineral density (BMD) has been reported in both paediatric and adult patients with non‐alcoholic fatty liver disease (NAFLD). The mechanisms behind the reduced BMD in NAFLD are still not completely understood.

Aim

To provide a critical overview of the pathophysiological pathways linking NAFLD, reduced BMD and osteoporosis, with a special focus on the alterations of soluble mediators which could link fat accumulation in the liver with bone health. The MEDLINE database was searched by a combination of keywords: non‐alcoholic fatty liver disease OR hepatic steatosis OR metabolic syndrome OR insulin resistance AND bone mineral density OR osteoporosis OR bone AND biomarkers OR serum marker.

Results

Several factors that may influence bone mineralisation and the increased risk of osteoporosis in NAFLD can be discussed. These include the release of cytokines from the inflamed liver which may influence the bone microenvironment, vitamin D deficiency, and limited physical activity. Circulating markers of bone metabolism, including osteopontin, osteoprotegerin, osteocalcin and fetuin‐A, have been found to be altered in patients with NAFLD.

Conclusion

A better understanding of the mechanisms that link bone metabolism and the liver may open a new frontier to fight two highly prevalent conditions like NAFLD and osteoporosis.
Haemodynamics in women with untreated pre‐eclampsia*
Authors: Dennis A. T. , Castro J. , Carr C. , Simmons S. , Permezel M. , Royse C.
Published: June 2012

This study aimed to compare the haemodynamics in healthy pregnant women with the haemodynamics in women with untreated pre‐eclampsia, to determine the cardiovascular reason for hypertension in pre‐eclampsia. 40 women with untreated pre‐eclampsia, 40 matched healthy pregnant women and 20 non‐pregnant women were studied using transthoracic echocardiography. Untreated pre‐eclampsia demonstrated (mean (SD), healthy non‐pregnant vs healthy pregnant vs untreated pre‐eclampsia) increased cardiac output (3400 (752) vs 4109 (595) vs 4789 (1416) ml.min−1, p = 0.002), increased stroke volume (53 (10) vs 53 (8) vs 59 (13) ml, p = 0.04), increased fractional shortening (35 (5) vs 35 (7) vs 41 (8) %, p = 0.006), increased fractional area change (57 (7) vs 57 (9) vs 65 (9) %, p = 0.002) and increased systemic vascular resistance (2116 (457) vs 1613 (315) vs 2016 (625) dyne.s.cm−5, p = 0.001). Mitral E/septal e′ was higher (6.0 (1.1) vs 6.7 (1.3) vs 10.4 (2.4), p = 0.002) and left atrial size increased (3.2 (0.3) vs 3.8 (0.4) vs 4.0 (0.4) cm, p = 0.002). Hypertension in untreated pre‐eclampsia is due to increased cardiac output and mild vasoconstriction, with increased inotropy and reduced diastolic function.
Management of pre‐eclampsia: issues for anaesthetists
Authors: Dennis A. T.
Published: June 2012

Pre‐eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deaths are preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of the current literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASE and the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre‐eclampsia, preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia, anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. The disease is defined within the context of hypertensive diseases, and early recognition of pre‐eclampsia and its complications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recording of observations including the use of transthoracic echocardiography is discussed. The importance of the treatment of systolic blood pressure > 180 mmHg and the use of intravenous antihypertensive medication as well as the use of parenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenous fluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia for birth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acute pulmonary oedema and the use of pharmacological agents in the setting of breastfeeding.
Multidisciplinary guidelines for the management of tracheostomy and laryngectomy airway emergencies
Authors: McGrath B. A. , Bates L. , Atkinson D. , Moore J. A.
Published: June 2012

Adult tracheostomy and laryngectomy airway emergencies are uncommon, but do lead to significant morbidity and mortality. The National Tracheostomy Safety Project incorporates key stakeholder groups with multi‐disciplinary expertise in airway management. , the Intensive Care Society, the Royal College of Anaesthetists, ENT UK, the British Association of Oral and Maxillofacial Surgeons, the College of Emergency Medicine, the Resuscitation Council (UK) the Royal College of Nursing, the Royal College of Speech and Language Therapists, the Association of Chartered Physiotherapists in Respiratory Care and the National Patient Safety Agency. Resources and emergency algorithms were developed by consensus, taking into account existing guidelines, evidence and experiences. The stakeholder groups reviewed draft emergency algorithms and feedback was also received from open peer review. The final algorithms describe a universal approach to managing such emergencies and are designed to be followed by first responders. The project aims to improve the management of tracheostomy and laryngectomy critical incidents.
Mitochondrial DNA D‐loop sequence variation in maternal lineages of Iranian native horses
Authors: Moridi M. , Masoudi A. A. , Vaez Torshizi R. , Hill E. W.
Published: June 2012

To understand the origin and genetic diversity of Iranian native horses, mitochondrial DNA (mtDNA) D‐loop sequences were generated for 95 horses from five breeds sampled in eight geographical locations in Iran. Sequence analysis of a 247‐bp segment revealed a total of 27 haplotypes with 38 polymorphic sites. Twelve of 19 mtDNA haplogroups were identified in the samples. The most common haplotypes were found within haplogroup X2. Within‐population haplotype and nucleotide diversities of the five breeds ranged from 0.838 ± 0.056 to 0.974 ± 0.022 and 0.011 ± 0.002 to 0.021 ± 0.001 respectively, indicating a relatively high genetic diversity in Iranian horses. The identification of several ancient sequences common between the breeds suggests that the lineage of the majority of Iranian horse breeds is old and obviously originated from a vast number of mares. We found in all native Iranian horse breeds lineages of the haplogroups D and K, which is concordant with the previous findings of Asian origins of these haplogroups. The presence of haplotypes E and K in our study also is consistent with a geographical west–east direction of increasing frequency of these haplotypes and a genetic fusion in Iranian horse breeds.
Tumourigenic characteristics of embryonal carcinoma cells as a model for studying tumour progression of human embryonic stem cells
Authors: Yang S. , Lin G. , Deng L. , Lu G.‐X.
Published: June 2012

Objectives

The objective of this study was to compare tumourigenic characteristics of human embryonic stem cells (HESCs) and embryonal carcinoma cells (ECCs) to identify a robust and simple model for studying certain aspects of cell transformation and tumourigenesis, in tumour progression of HESCs.

Materials and methods

SSEA‐3 positive ECCs (NTERA‐2) cells were identified and compared to HESCs (ch
HES‐20) in terms of pluripotency and differentiation capacity, growth characteristics, gene expression profiles and signalling pathways.

Results

Our results showed that NTERA‐2 cells shared similarities in expression markers of pluripotency to ch
HES‐20 cells. However, NTERA‐2 cells also expressed some markers of differentiation and had a tendency to differentiate towards ectodermal endpoints. We identified NTERA‐2 cells with higher S‐phase fraction in cell cycle distribution, anti‐apoptosis markers and robust self‐renewal ability, compared to ch
HES‐20 cells. Microarray analysis and real‐time PCR results showed that some oncogenes were up‐regulated and tumour‐suppression genes were down‐regulated, whereas pluripotency‐related genes were up‐regulated and differentiation‐related genes were down‐regulated, and that Wnt and Notch signalling pathways were activated during progression from ES cells to EC cells.

Conclusion

Tumourigenic characteristics of ECCs may provide a valuable insight into possible tumour progression of HESCs.
Histopathological study comparing upstream binding factor expression and AgNOR staining
Authors: Torres‐Montaner A. , Huq M.
Published: June 2012

AgNOR staining has been in past years, the subject of numerous publications, which have failed to reach agreement regarding its usefulness as a proliferation marker. This silver staining method does not react with NORs (actual chromosome regions containing rRNA (ribosomal RNA) genes), but with proteins associated with them, whose quantity increases in parallel with ribosome biogenesis. The transcription factor UBF (upstream binding factor) is associated with NORs and has an important regulatory role in rRNA synthesis as cofactor of RNA polymerase I. Recent research has revealed an additional cytoarchitectural function of UBF in decondensing r‐chromatin (ribosomal‐chromatin). Immune detection of UBF expression and AgNOR counts are closely correlated as both techniques identify substrates in or closely adjacent to NORs. However, contrary to AgNOR dots, the UBF signal disappears in cells which undergo apoptosis or terminal differentiation. These features imply that UBF evaluation would reflect tumour cell proliferation (growth fraction) more accurately than AgNOR counts. Here we also show that immunohistochemical staining of UBF may reveal distinct active NORs with open, decondensed chromatin and we hypothesize that the large stretches of decondensed r‐chromatin revealed by UBF staining may correspond to clusters seen after silver staining and, conversely, shorter areas of decondensed r‐chromatin should match the small AgNOR grains typically found in some tumour types. The length of decondensed r‐chromatin may be a reflection of the ratio of active to silent r‐RNA genes.
Trait sorting in Daphnia colonising man‐made lakes
Authors: ALLEN MICHAEL R. , THUM RYAN A. , VANDYKE JESSICA N. , CÁCERES CARLA E.
Published: June 2012

1. We used a zooplankton metacommunity to ask how dispersal, genetic drift and selection act to determine the local and regional distributions of trait variation. Since the formation of the lakes 80 years ago, cladoceran species have sorted into local assemblages that cluster by lake depth. Given this species sorting, we ask whether intraspecific variation in an ecologically important phenotypic trait – body size – has sorted as well.

2. We quantified changes in body size through time by measuring ephippia from D. pulicaria, D. dentifera and D. ambigua recovered from sediment cores from two lakes. We then estimated mean body size of contemporary populations of two competing species, Daphnia pulicaria and D. dentifera, in a laboratory common garden experiment. Finally, we used microsatellite loci to characterise genetic diversity and gene flow among local sites in the metacommunity.

3. Body size was variable both within and among years for the three species of Daphnia examined using sediment cores. For two lakes where we examined body size distributions through time, we observed a significant shift in body size of the first species to arrive after colonisation by other Daphnia species, which suggests selection has occurred historically.

4. Despite heritable variation in body size in the laboratory, evidence for trait sorting was only found for D. pulicaria, which was larger in deeper lakes. Mean body size varied among lakes, but did not sort relative to depth for D. dentifera.

5. Microsatellite data indicated that neutral genetic diversity was low in the region; only 27% of the individuals assayed were unique multi‐locus genotypes. We also found significant patterns of isolation by distance for both species. However, population structure was stronger in D. dentifera than in D. pulicaria. Hence, we conclude that a limited number of colonists have successfully invaded this metacommunity, and those genotypes arriving in this new region have experienced significant dispersal limitation among local sites.

6. Overall, while dispersal and selection have clearly led to the development of predictable community assemblages related to depth in this metacommunity, the distribution of phenotypic traits within species can differ substantially even between two trophically similar species. Our results highlight the complex roles of colonisation history, dispersal, selection and stochasticity in determining inter‐ and intra‐specific patterns in metacommunities.
A fast integral equation solver for 3D induction well logging in formations with large conductivity contrasts
Authors: Nie Xiao Chun , Yuan Ning , Liu Richard
Published: July 2012

Simulation of induction logging responses in formations with large conductivity contrasts is an important but challenging problem due to the singularity of a linear system caused by large contrasts. Also, three‐dimensional (3D) analysis of complex geophysical structures usually encounters high computational demands. In this paper, a pre‐corrected fast Fourier transform (pFFT)‐accelerated integral equation method is applied to overcome these difficulties. In the approach, the entire formation is included in the solution domain. The volume integral equation is set up in the region based on the fact that the total field is the summation of the excitation field and the secondary field. The emitted field by the transmitter coil (treated as a magnetic dipole) is regarded as the excitation of the system. Then the method of moments (MoM) is used to solve the integral equation. To reduce the high computational requirements of the MoM, the pFFT method is used to speed up the solution of the matrix equation and reduce the memory requirement as well. The resultant method is capable of computing induction logging problems involving large and complex formations. For problems with high conductivity contrasts, the solution of the matrix equation usually converges very slow or even fails to converge due to the large condition number of the coefficient matrix. To overcome this difficulty, an incomplete LU pre‐conditioner is used to significantly speed up the convergence of the matrix equation, thus further reducing the computation time. Numerical results show that the present method is efficient and flexible for 3D simulation of induction logging and is specifically superior for problems with high conductivity contrasts.
Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification
Authors: Sassa Naoto , Tsuzuki Toyonori , Fukatsu Akitoshi , Majima Tsuyoshi , Kimura Tohoru , Nishikimi Toshinori , Yoshino Yasushi , Hattori Ryohei , Gotoh Momokazu
Published: June 2012

Sassa N, Tsuzuki T, Fukatsu A, Majima T, Kimura T, Nishikimi T, Yoshino Y, Hattori R & Gotoh M (2012) Histopathology61, 620–628

Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification

Aims:  The prognosis of urothelial carcinoma of the renal pelvis (UCRP) is heterogeneous, especially in pT3 patients. The degree of tumour parenchymal invasion is not considered for pathological tumour (pT) staging. The aim of this study was to investigate whether quantitative assessment of invasion provides a better estimation of prognosis for UCRP in pT3 patients.

Methods and results:  We reclassified pT3 cases into two subcategories: pT3a, in which UCRP extended only into the renal medulla; and pT3b, in which UCRP extended into the renal cortex and/or in which UCRP exhibited peripelvic fat invasion. We examined our proposed pT classification and other pathological parameters, including necrosis, lymph–vascular invasion (LVI), 1973 World Health Organization (WHO) grading, WHO/International Society of Urological Pathology grading, adjuvant chemotherapy, and pathological lymph node metastasis (pN). The study included 275 patients. Among 96 patients with pT3, there was a statistically significant difference between the pT3a and pT3b subcategories in cancer‐specific survival (P < 0.001). Our proposed pT classification, as well as necrosis, LVI, 1973 WHO grading, and pN, demonstrated prognostic differences in univariate analysis, whereas in multivariate analysis, only our proposed classification (P = 0.008) and pN (P = 0.002) were statistically significant.

Conclusions:  The pT3b subcategories should be regarded as true pT3, having the established features of that stage, whereas pT3a has a better prognosis.
Sustained sleep fragmentation affects brain temperature, food intake and glucose tolerance in mice
Authors: BAUD MAXIME O. , MAGISTRETTI PIERRE J. , PETIT JEAN‐MARIE
Published: June 2012

Sleep fragmentation is present in numerous sleep pathologies and constitutes a major feature of patients with obstructive sleep apnea. A prevalence of metabolic syndrome, diabetes and obesity has been shown to be associated to obstructive sleep apnea. While sleep fragmentation has been shown to impact sleep homeostasis, its specific effects on metabolic variables are only beginning to emerge. In this context, it is important to develop realistic animal models that would account for chronic metabolic effects of sleep fragmentation. We developed a 14‐day model of instrumental sleep fragmentation in mice, and show an impact on both brain‐specific and general metabolism. We first report that sleep fragmentation increases food intake without affecting body weight. This imbalance was accompanied by the inability to adequately decrease brain temperature during fragmented sleep. In addition, we report that sleep‐fragmented mice develop glucose intolerance. We also observe that sleep fragmentation slightly increases the circadian peak level of glucocorticoids, a factor that may be involved in the observed metabolic effects. Our results confirm that poor‐quality sleep with sustained sleep fragmentation has similar effects on general metabolism as actual sleep loss. Altogether, these results strongly suggest that sleep fragmentation is an aggravating factor for the development of metabolic dysfunctions that may be relevant for sleep disorders such as obstructive sleep apnea.
Genome‐wide single nucleotide polymorphism analysis reveals recent genetic introgression from domestic pigs into Northwest European wild boar populations
Authors: GOEDBLOED D. J. , MEGENS H.J. , Van HOOFT P. , HERRERO‐MEDRANO J. M. , LUTZ W. , ALEXANDRI P. , CROOIJMANS R. P. M. A. , GROENEN M. , Van WIEREN S. E. , YDENBERG R. C. , PRINS H. H. T.
Published: June 2012

Present‐day genetic introgression from domestic pigs into European wild boar has been suggested in various studies. However, no hybrids have been identified beyond doubt mainly because available methods were unable to quantify the extent of introgression and rule out natural processes. Genetic introgression from domestic pigs may have far‐reaching ecological consequences by altering traits like the reproduction rate or immunology of wild boar. In this study, we demonstrate a novel approach to investigate genetic introgression in a Northwest (NW) European wild boar data set using a genome‐wide single nucleotide polymorphism (SNP) assay developed for domestic pigs. We quantified the extent of introgression using allele frequency spectrum analysis, in silico hybridization simulations and genome distribution patterns of introgressed SNPs. Levels of recent introgression in the study area were expected to be low, as pig farming practices are prevailingly intensive and indoors. However, evidence was found for geographically widespread presence of domestic pig SNPs in 10% of analysed wild boar. This was supported by the identification of two different pig mitochondrial DNA haplotypes in three of the identified hybrid wild boar, suggesting that introgression had occurred from multiple sources (pig breeds). In silico hybridization simulations showed that the level of introgression in the identified hybrid wild boar is equivalent to first‐generation hybrids until fifth‐generation backcrosses with wild boar. The distribution pattern of introgressed SNPs supported these assignments in four of nine hybrids. The other five hybrids are considered advanced‐generation hybrids, resulting from interbreeding among hybrid individuals. Three of nine hybrids were genetically associated with a different wild boar population than the one in which they were sampled. This discrepancy suggests that genetic introgression has occurred through the escape or release of an already hybridized farmed wild boar stock. We conclude that genetic introgression from domestic pigs into NW European wild boar populations is more recent and more common than expected and that genome‐wide SNP analysis is a promising tool to quantify recent hybridization in free‐living populations.
Post‐translational regulation of acid invertase activity by vacuolar invertase inhibitor affects resistance to cold‐induced sweetening of potato tubers
Authors: MCKENZIE MARIAN J. , CHEN RONAN K. Y. , HARRIS JOHN C. , ASHWORTH MATTHEW J. , BRUMMELL DAVID A.
Published: June 2012

Cold‐induced sweetening (CIS) is a serious post‐harvest problem for potato tubers, which need to be stored cold to prevent sprouting and pathogenesis in order to maintain supply throughout the year. During storage at cold temperatures (below 10 °C), many cultivars accumulate free reducing sugars derived from a breakdown of starch to sucrose that is ultimately cleaved by acid invertase to produce glucose and fructose. When affected tubers are processed by frying or roasting, these reducing sugars react with free asparagine by the Maillard reaction, resulting in unacceptably dark‐coloured and bitter‐tasting product and generating the probable carcinogen acrylamide as a by‐product. We have previously identified a vacuolar invertase inhibitor (INH2) whose expression correlates both with low acid invertase activity and with resistance to CIS. Here we show that, during cold storage, overexpression of the INH2 vacuolar invertase inhibitor gene in CIS‐susceptible potato tubers reduced acid invertase activity, the accumulation of reducing sugars and the generation of acrylamide in subsequent fry tests. Conversely, suppression of vacuolar invertase inhibitor expression in a CIS‐resistant line increased susceptibility to CIS. The results show that post‐translational regulation of acid invertase by the vacuolar invertase inhibitor is an important component of resistance to CIS.
Gene expression patterns underlying changes in xylem structure and function in response to increased nitrogen availability in hybrid poplar
Authors: PLAVCOVÁ LENKA , HACKE UWE G. , ALMEIDA‐RODRIGUEZ ADRIANA M. , LI ERYANG , DOUGLAS CARL J.
Published: June 2012

Nitrogen availability has a strong influence on plant growth and development. In this study, we examined the effect of nitrogen availability on xylogenesis in hybrid poplar (Populus trichocarpa × deltoides H11‐11). Saplings of hybrid poplar were fertilized for 33 d with either high or adequate levels of ammonium nitrate. We observed enhanced radial growth, wider vessels and fibres and thinner fibre walls in the secondary xylem of high N relative to adequate N plants. These anatomical differences translated into altered hydraulic properties with xylem being more transport efficient but also more vulnerable to drought‐induced cavitation in high N plants. The changes in xylem structure and function were associated with differences in gene expression as revealed by the transcriptome analysis of the developing xylem region. We found 388 genes differentially expressed (fold change ±1.5, P‐value ≤ 0.05), including a number of genes putatively involved in nitrogen and carbohydrate metabolism and various aspects of xylem cell differentiation. Several genes encoding known transcriptional regulators of secondary cell wall deposition were down‐regulated in high N plants, corresponding with thinner secondary cell walls in these plants. The results of this study provide us with gene candidates potentially affecting xylem hydraulic and structural traits.
The HLA‐DRB1 gene and Graves disease in Taiwanese children: a case‐control and family‐based study
Authors: Wu Y.‐L. , Chang T.‐Y. , Chu C.‐C. , Huang C.‐Y. , Lo F.‐S. , Ting W.‐H. , Lin C.‐H. , Lin M. , Chiu P.‐C. , Lin C.‐L. , Chen W.‐F. , Lee Y.‐J.
Published: June 2012

Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA‐DRB1 alleles and Taiwanese children with GD by both case‐control and family‐based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA‐DRB1 genotyping was performed by polymerase chain reaction and sequence‐based typing assays. We found that DRB1*09:01 (OR = 2.60, 95% CI 2.02–3.35, Pc = 6.55 × 10−13) was associated with GD risk, while DRB1*12:02 (OR = 0.32, 95% CI 0.20–0.53, Pc = 4.55 × 10−5) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13–6.22, Pc = 1.0 × 10−5) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05–0.42, Pc = 1.7 × 10−3). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA‐DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.
Bone Morphology of the Hind Limbs in Two Caviomorph Rodents
Authors: de Araújo F. A. P. , Sesoko N. F. , Rahal S. C. , Teixeira C. R. , Müller T. R. , Machado M. R. F.
Published: June 2012

In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the
Cuniculus paca (Linnaeus, 1766) and
Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full‐coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of
Rattus norvegicus (Berkenhout, 1769) and domestic
Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in
Cuniculus paca and
Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species.
Altered Prey Responses in Round Goby from Contaminated Sites
Authors: Marentette Julie R. , Balshine Sigal
Published: June 2012

Although prey must move to forage, escape predation or gain information about predation risk, movement itself enhances the risk of predation by increasing visibility of prey and encounter rates with predators. Animals subjected to stressors often show altered behaviour; a widely cited effect of contaminant exposure is an increase in vulnerability to predation, which may be mediated by an increase in risky behaviour. Round goby are invasive fish that typically rely on crypsis and sheltering (low‐activity behaviours) to avoid predators. We collected round goby from contaminated sites and tested whether they showed signs of altered risk‐taking compared with fish from a less contaminated reference site. We subjected the fish to a simulated predation event (a motor‐operated model bass) under both diurnal and nocturnal conditions. Fish from contaminated sites showed lower overall activity levels, but also failed to reduce activity following an attack, unlike fish from the reference site. The intensity of effects varied with diel period. Males, but not females, from contaminated sites showed reduced likelihood of darting during an attack, while females, but not males, from contaminated sites were less likely to approach the predator. Sex differences in round goby risk‐taking may reflect sex‐specific selection pressures on activities promoting predation risk. With the exception of post‐attack activity, round goby from contaminated sites generally showed signs of reduced risk‐taking. If contaminant exposure increases goby vulnerability to predators, it may be occurring through behavioural mechanisms other than impacts on risky prey responses.