bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing the effects of the 2002 McNally fire on air quality in the San Joaquin Valley and southern Sierra Nevada, California
Authors: Cisneros Ricardo , Schweizer Donald , Zhong Sharon , Hammond Katharine , Perez Miguel A. , Guo Qinghua , Traina Samuel , Bytnerowicz Andrzej , Bennett Deborah H.
Published: July 2012

Smoke from wildfires can expose individuals and populations to elevated levels of particulate matter (PM) and ozone (O3). Between 21 July and 26 August 2002, the McNally Fire burned over 150000 acres (61000 ha). The fire occurred in the Sequoia National Forest, in the southern Sierra Nevada of California. This study evaluated the effects of the McNally Fire on air quality, specifically particles <10 μm in diameter (PM10) and O3. Downwind of the fire on the eastern side of the Sierra Nevada, 24-h concentrations of PM10 more than doubled. The PM10 federal standard was exceeded four times during the fire. Violations of the California PM10 standard increased drastically during the fire. The California PM10 standard was violated six times before the fire and 164 times during the fire. Most of the PM10 exceedances occurred at the Kernville Work Center and sites east of the fire. Compared with the other sites, the highest 2-week average O3 concentrations occurred in the eastern part of the Sierra Nevada and north of the fire, where O3 increased by a factor of two at two locations.
Olfaction shapes host–parasite interactions in parasitic nematodes
Authors: Dillman Adler R. , Guillermin Manon L. , Lee Joon Ha , Kim Brian , Sternberg Paul W. , Hallem Elissa A.
Published: August 2012

Many parasitic nematodes actively seek out hosts in which to complete their lifecycles. Olfaction is thought to play an important role in the host-seeking process, with parasites following a chemical trail toward host-associated odors. However, little is known about the olfactory cues that attract parasitic nematodes to hosts or the behavioral responses these cues elicit. Moreover, what little is known focuses on easily obtainable laboratory hosts rather than on natural or other ecologically relevant hosts. Here we investigate the olfactory responses of six diverse species of entomopathogenic nematodes (EPNs) to seven ecologically relevant potential invertebrate hosts, including one known natural host and other potential hosts collected from the environment. We show that EPNs respond differentially to the odor blends emitted by live potential hosts as well as to individual host-derived odorants. In addition, we show that EPNs use the universal host cue CO
2
as well as host-specific odorants for host location, but the relative importance of CO
2
versus host-specific odorants varies for different parasite–host combinations and for different host-seeking behaviors. We also identified host-derived odorants by gas chromatography-mass spectrometry and found that many of these odorants stimulate host-seeking behaviors in a species-specific manner. Taken together, our results demonstrate that parasitic nematodes have evolved specialized olfactory systems that likely contribute to appropriate host selection.
A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt
Authors: Aoki Masahiro , Blazek Erik , Vogt Peter K.
Published: July 2012

The oncoproteins P3k (homolog of the catalytic subunit of class IA phosphoinositide 3-kinase) and Akt (protein kinase B) induce oncogenic transformation of chicken embryo fibroblasts. The transformed cells show constitutive phosphorylation of the positive regulator of translation p70S6 kinase (S6K) and of the eukaryotic initiation factor 4E-BP1 binding protein (4E-BP1), a negative regulator of translation. Phosphorylation activates S6K and inactivates 4E-BP1. A mutant of Akt that retains kinase activity but does not induce phosphorylation of S6K or of 4E-BP1 fails to transform chicken embryo fibroblasts, suggesting a correlation between the oncogenicity of Akt and phosphorylation of S6K and 4E-BP1. The macrolide antibiotic rapamycin effectively blocks oncogenic transformation induced by either P3k or Akt but does not reduce the transforming activity of 11 other oncoproteins. Rapamycin inhibits the kinase mTOR, an important regulator of translation, and this inhibition requires binding of the antibiotic to the immunophilin FKBP12. Displacement of rapamycin from FKBP12 relieves the inhibition of mTOR and also restores P3k-induced transformation. These data are in accord with the hypothesis that transformation by P3k or Akt involves intervention in translational controls.
Protein sequence signatures support the African clade of mammals
Authors: van Dijk Marjon A. M. , Madsen Ole , Catzeflis François , Stanhope Michael J. , de Jong Wilfried W. , Pagel Mark
Published: July 2012

DNA sequence evidence supports a superordinal clade of mammals that comprises elephants, sea cows, hyraxes, aardvarks, elephant shrews, golden moles, and tenrecs, which all have their origins in Africa, and therefore are dubbed Afrotheria. Morphologically, this appears an unlikely assemblage, which challenges—by including golden moles and tenrecs—the monophyly of the order Lipotyphla (Insectivora). We here identify in three proteins unique combinations of apomorphous amino acid replacements that support this clade. The statistical support for such “sequence signatures” as unambiguous synapomorphic evidence for the naturalness of the Afrotherian clade is reported. Using likelihood, combinatorial, and Bayesian methods we show that the posterior probability of the mammalian tree containing the Afrotherian clade is effectively 1.0, based on conservative assumptions. Presenting sequence data for another African insectivore, the otter shrewMicropotamogale lamottei, we demonstrate that such signatures are diagnostic for including newly investigated species in the Afrotheria. Sequence signatures provide “protein-morphological” synapomorphies that may aid in visualizing monophyletic groupings.
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
Authors: Li Cheng , Wong Wing Hung
Published: July 2012

Recent advances in cDNA and oligonucleotide DNA arrays have made it
possible to measure the abundance of mRNA transcripts for many genes
simultaneously. The analysis of such experiments is nontrivial because
of large data size and many levels of variation introduced at different
stages of the experiments. The analysis is further complicated by the
large differences that may exist among different probes used to
interrogate the same gene. However, an attractive feature of
high-density oligonucleotide arrays such as those produced by
photolithography and inkjet technology is the standardization of chip
manufacturing and hybridization process. As a result, probe-specific
biases, although significant, are highly reproducible and predictable,
and their adverse effect can be reduced by proper modeling and analysis
methods. Here, we propose a statistical model for the probe-level data,
and develop model-based estimates for gene expression indexes. We also
present model-based methods for identifying and handling
cross-hybridizing probes and contaminating array regions. Applications
of these results will be presented elsewhere.
Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor α
Authors: Macchia Paolo E. , Takeuchi Yoko , Kawai Tomoko , Cua Kevin , Gauthier Karine , Chassande Olivier , Seo Hisao , Hayashi Yoshitaka , Samarut Jacques , Murata Yoshiharu , Weiss Roy E. , Refetoff Samuel
Published: July 2012

Only three of the four thyroid hormone receptor (TR)
isoforms, α1, β1, and β2, bind thyroid hormone (TH) and are
considered to be true TRs. TRα2 binds to TH response elements on DNA,
but its role
in vivo
is still unknown. We produced mice
completely deficient in TRα (TRα
o/o
) that maintain
normal serum thyroid-stimulating hormone (TSH) concentration despite
low serum thyroxine (T
4
), suggesting increased sensitivity
to TH. We therefore examined the effects of TH
(L-3,3′,5-triiodothyronine, L-T
3
) given to TH-deprived and
to intact TRα
o/o
mice. Controls were wild-type (WT) mice
of the same strain and mice resistant to TH due to deficiency in TRβ
(TRβ
−/−
). In liver, T
3
produced
significantly greater responses in TRα
o/o
and smaller
responses in TRβ
−/−
as compared with WT mice. In
contrast, cardiac responses to L-T
3
were absent or reduced
in TRα
o/o
, whereas they were similar in WT and
TRβ
−/−
mice, supporting the notion that TRα1 is the
dominant TH-dependent TR isoform in heart. 5-Triiodothyronine
(L-T
3
) given to intact mice produced a greater suppression
of serum T
4
in TRα
o/o
than it did in WT mice
and reduced by a greater amount the TSH response to TSH-releasing
hormone. This is an
in vivo
demonstration that a TR
deficiency can enhance sensitivity to TH. This effect is likely due to
the abrogation of the constitutive “silencing” effect of TRα2
in tissues expressing the TRβ isoforms.
2-Aminopurine fluorescence quenching and lifetimes: Role of base stacking
Authors: Jean John M. , Hall Kathleen B.
Published: July 2012

2-Aminopurine (2AP) is a fluorescent analog of guanosine and
adenosine and has been used to probe nucleic acid structure and
dynamics. Its spectral features in nucleic acids have been interpreted
phenomenologically, in the absence of a rigorous electronic description
of the context-dependence of 2AP fluorescence. Now, by using
time-dependent density functional theory, we describe the excited-state
properties of 2AP in a B-form dinucleotide stacked with guanosine,
adenosine, cytosine, or thymine. Calculations predict that 2AP
fluorescence is quenched statically when stacked with purines, because
of mixing of the molecular orbitals in the ground state. In contrast,
quenching is predicted to be dynamic when 2AP is stacked with
pyrimidines, because of formation of a low-lying dark excited state.
The different quenching mechanisms will result in different
experimentally measured fluorescence lifetimes and quantum yields.
Translation in global news agencies
Authors: Bielsa Esperança
Published: July 2012

This article presents news agencies as vast translation agencies, structurally designed to achieve fast and reliable translations of large amounts of information. It maintains that translation is of the utmost importance in the news agencies and that it is inseparable from other journalistic practices that intervene in the production of news. Rejecting the naïve view that translations are often improvised by people who do not have the necessary training, the article claims that the news editor has the specific skills required for the elaboration of such translations, and that the organisation of news agencies has been conceived in order to facilitate communication flows between different linguistic communities so as to reach global publics with maximum speed and efficiency. If news translation has traditionally been neglected by Translation Studies it is because it usually is in the hands of journalists rather than translators. A detailed examination of the nature and processes involved in news translation problematises central concepts such as authorship and equivalence and leads Translation Studies in new directions.
Writing grammar rather than tone
Authors: Roberts David , Walter Stephen L.
Published: July 2012

Some orthographies represent tone phonemically by means of diacritics; others favor zero marking. Neither solution is entirely satisfactory. The former leads to graphic overload; the latter to a profusion of homographs; both may reduce fluency. But there is a ‘third way’: to highlight the grammar rather than the tone system itself. To test this approach, we developed two experimental strategies for Kabiye: a grammar orthography and a tone orthography. Both are modifications of the standard orthography that does not mark tone. We tested these in a quantitative experiment involving literate L1 speakers that included dictation and spontaneous writing. Writers of the grammar orthography perform faster and more accurately than writers of the tone orthography, suggesting that they have an awareness of the morphological and syntactic structure of their language that may exceed their awareness of its phonology. This suggests that languages with grammatical tone might benefit from grammatical markers in the orthography. Keywords:﻿﻿ tone; grammar; orthography; African languages; quantitative experiment
The Overthrow of the Government of Mosaddeq Reconsidered
Authors: Azimi Fakhreddin
Published: July 2012

The overthrow of the government of Mosaddeq has received considerable attention, scholarly and otherwise. The scholarly explanations differ in emphasis, but not in the general contours, particularly regarding the significant role of the Anglo-American secret services. There have also long been attempts to portray the overthrow of Mosaddeq as an isolated event taking place on 19 August 1953 and representing a conflation of royalist and traditionalist sentiments among soldiers and civilians. More recently it has been contended that it was not the Anglo-American secret services but the clerical nexus—prompted by Ayatollah Borujerdi, the highest religious authority in the country—which played the crucial role. This paper argues against reducing the overthrow of Mosaddeq's government to the events of 19 August, and views it as a protracted process. It further argues that assertions regarding the crucial and active role of Borujerdi are, on the basis of available evidence, untenable.
Blood Chemistry Values for Shovelnose and Lake Sturgeon
Authors: Sepúlveda Maria S. , Sutton Trent M. , Patrick Holly K. , Amberg Jon J.
Published: August 2012

Blood chemistry panels are commonly used for assessing the general health of vertebrate animals. Here, we present novel blood chemistry data for two North American sturgeon species, shovelnose sturgeon Scaphirhynchus platorynchus and lake sturgeon Acipenser fulvescens. Measurements were done using a portable chemistry analyzer (VetScan Analyzer; Abaxis). Among the plasma values measured (mean ± SD for shovelnose and lake sturgeon, respectively) were total proteins (3.7 ± 0.9 and 2.8 ± 0.4 g/dL), albumin (2.0 ± 0.5 and 1.1 ± 0.2 g/dL), globulin (1.7 ± 0.7 and 1.7 ± 0.3 g/dL), glucose (107 ± 46 and 62 ± 9.7 mg/dL), sodium (Na+; 132 ± 3.6 and 150 ± 14 mEq/L), potassium (K+; 3.5 ± 0.2 and 2.8 ± 1.7 mEq/L), phosphorus (10.4 ± 1.9 and 11.6 ± 3.6 mg/dL), and aspartate aminotransferase (AST; 676 ± 433 and 634 ± 234 IU/L). Higher values for total proteins, albumin, glucose, and Na+ in shovelnose sturgeon than in lake sturgeon probably are the result of handling stress. In addition, the plasma of male shovelnose sturgeon had higher concentrations of AST, glucose, and globulin than did that of females, whereas the plasma of females had higher concentrations of albumin and K+ than that of males. This study is the first to report blood chemistry data for shovelnose sturgeon. Robust blood chemistry databases can be used by aquaculturists and fish managers for monitoring sturgeon health.

Received July 8, 2011; accepted February 2, 2012
INTEGRATION – WHAT INTEGRATION?
Authors: Grötsch Florian , Schnabel Annette
Published: July 2012

Since the founding of the European Union, religion has become an increasingly important aspect in shaping European identity and thereby social cohesion in Europe. Social cohesion depends to a high degree on a successfully established distinction between ‘us’ and ‘them’. Religion became one important marker of such boundaries. However, religion works both as an individual-level and an EU-level property. In order to take religion into consideration on the level of individual religiousness and as an institutionalised framework, we combine an analysis of key documents of the European Commission with a quantitative analysis of individual attitudes towards Europe. This combination of methods enables us to track the ‘discovery of religion’ by the European Commission as a means for social cohesion and the potential of religion to create Europeanness among the EU-citizens. We focus on the crucial period between 1990 and 2000 in which the major system transformation from EEC to EU took place. The quantitative analysis is conducted as a multi-level analysis on the basis of the European Value Survey 1990 and 2000. The data reveal that in fact over a 10-year period, the European integration project has begun to evolve towards an identity project with religion as a key factor on both levels.
Revealing the role of CD4+ T cells in viral immunity
Authors: Sant Andrea J. , McMichael Andrew
Published: July 2012

Protective immunity to chronic and acute viral infection relies on both the innate and adaptive immune response. Although neutralizing antibody production by B cells and cytotoxic activity of CD8+ T cells are well-accepted components of the adaptive immune response to viruses, identification of the specific role of CD4+ T cells in protection has been more challenging to establish. Delineating the contribution of CD4+ T cells has been complicated by their functional heterogeneity, breadth in antigen specificity, transient appearance in circulation, and sequestration in tissue sites of infection. In this minireview, we discuss recent progress in identifying the multiple roles of CD4+ T cells in orchestrating and mediating the immune responses against viral pathogens. We highlight several recent reports, including one published in this issue, that have employed comprehensive and sophisticated approaches to provide new evidence for CD4+ T cells as direct effectors in antiviral immunity.
Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP
Authors: Tencerová Barbora , Zahradníková Alexandra , Gaburjáková Jana , Gaburjáková Marta
Published: July 2012

The synergic effect of luminal Ca2+, cytosolic Ca2+, and cytosolic adenosine triphosphate (ATP) on activation of cardiac ryanodine receptor (RYR2) channels was examined in planar lipid bilayers. The dose–response of RYR2 gating activity to ATP was characterized at a diastolic cytosolic Ca2+ concentration of 100 nM over a range of luminal Ca2+ concentrations and, vice versa, at a diastolic luminal Ca2+ concentration of 1 mM over a range of cytosolic Ca2+ concentrations. Low level of luminal Ca2+ (1 mM) significantly increased the affinity of the RYR2 channel for ATP but without substantial activation of the channel. Higher levels of luminal Ca2+ (8–53 mM) markedly amplified the effects of ATP on the RYR2 activity by selectively increasing the maximal RYR2 activation by ATP, without affecting the affinity of the channel to ATP. Near-diastolic cytosolic Ca2+ levels (<500 nM) greatly amplified the effects of luminal Ca2+. Fractional inhibition by cytosolic Mg2+ was not affected by luminal Ca2+. In models, the effects of luminal and cytosolic Ca2+ could be explained by modulation of the allosteric effect of ATP on the RYR2 channel. Our results suggest that luminal Ca2+ ions potentiate the RYR2 gating activity in the presence of ATP predominantly by binding to a luminal site with an apparent affinity in the millimolar range, over which local luminal Ca2+ likely varies in cardiac myocytes.
Regulation of Biosynthesis of Syringolin A, a Pseudomonas syringae Virulence Factor Targeting the Host Proteasome
Authors: Ramel Christina , Baechler Nando , Hildbrand Michel , Meyer Martin , Schädeli David , Dudler Robert
Published: August 2012

Many strains of the phytopathogenic bacterium Pseudomonas syringae pv. syringae synthesize the virulence factor syringolin A, which irreversibly inactivates the eukaryotic proteasome. Syringolin A, a peptide derivative, is synthesized by a mixed nonribosomal peptide/polyketide synthetase encoded by five clustered genes, sylA to sylE. Biosynthesis of syringolin A, previously shown to be dependent on the GacS/GacA two-component system, occurs in planta and in vitro but only under still culture conditions in a defined medium. Here, we show that the sylC, sylD, and sylE genes of P. syringae pv. syringae B301D-R form an operon transcribed by promoter sequences located between the sylCDE operon and the sylB gene residing on opposite strands. Assays of overlapping sylB and sylCDE promoter deletions translationally fused to the lacZ gene defined promoter sequences required for gene activity both in vitro and in planta. Activation of both promoters depended on the sylA gene encoding a helix-turn-helix (HTH) LuxR-type transcription factor which was shown to directly bind to the promoters. Activity of the sylA gene, in turn, required a functional salA gene, which also encodes an HTH LuxR-type transcription factor. Furthermore, evidence is presented that acyl-homoserine lactone-mediated quorum-sensing regulation is not involved in syringolin A biosynthesis but that oxygen concentration appears to play a role.
Indole-3-Acetaldoxime-Derived Compounds Restrict Root Colonization in the Beneficial Interaction Between Arabidopsis Roots and the Endophyte Piriformospora indica
Authors: Nongbri Pyniarlang L. , Johnson Joy Michal , Sherameti Irena , Glawischnig Erich , Halkier Barbara Ann , Oelmüller Ralf
Published: August 2012

The growth-promoting and root-colonizing endophyte Piriformospora indica induces camalexin and the expression of CYP79B2, CYP79B3, CYP71A13, PAD3, and WRKY33 required for the synthesis of indole-3-acetaldoxime (IAOx)-derived compounds in the roots of Arabidopsis seedlings. Upregulation of the mRNA levels by P. indica requires cytoplasmic calcium elevation and mitogen-activated protein kinase 3 but not root-hair-deficient 2, radical oxygen production, or the 3-phosphoinositide-dependent kinase 1/oxidative signal-inducible 1 pathway. Because P. indica–mediated growth promotion is impaired in cyp79B2 cyp79B3 seedlings, while pad3 seedlings—which do not accumulate camalexin—still respond to the fungus, IAOx-derived compounds other than camalexin (e.g., indole glucosinolates) are required during early phases of the beneficial interaction. The roots of cyp79B2 cyp79B3 seedlings are more colonized than wild-type roots, and upregulation of the defense genes pathogenesis-related (PR)-1, PR-3, PDF1.2, phenylalanine ammonia lyase, and germin indicates that the mutant responds to the lack of IAOx-derived compounds by activating other defense processes. After 6 weeks on soil, defense genes are no longer upregulated in wild-type, cyp79B2 cyp79B3, and pad3 roots. This results in uncontrolled fungal growth in the mutant roots and reduced performance of the mutants. We propose that a long-term harmony between the two symbionts requires restriction of root colonization by IAOx-derived compounds.
Evolution of trees and mycorrhizal fungi intensifies silicate mineral weathering
Authors: Quirk Joe , Beerling David J. , Banwart Steve A. , Kakonyi Gabriella , Romero-Gonzalez Maria E. , Leake Jonathan R.
Published: August 2012

Forested ecosystems diversified more than 350 Ma to become major engines of continental silicate weathering, regulating the Earth's atmospheric carbon dioxide concentration by driving calcium export into ocean carbonates. Our field experiments with mature trees demonstrate intensification of this weathering engine as tree lineages diversified in concert with their symbiotic mycorrhizal fungi. Preferential hyphal colonization of the calcium silicate-bearing rock, basalt, progressively increased with advancement from arbuscular mycorrhizal (AM) to later, independently evolved ectomycorrhizal (EM) fungi, and from gymnosperm to angiosperm hosts with both fungal groups. This led to ‘trenching’ of silicate mineral surfaces by AM and EM fungi, with EM gymnosperms and angiosperms releasing calcium from basalt at twice the rate of AM gymnosperms. Our findings indicate mycorrhiza-driven weathering may have originated hundreds of millions of years earlier than previously recognized and subsequently intensified with the evolution of trees and mycorrhizas to affect the Earth's long-term CO
2
and climate history.
Using field data to test locust migratory band collective movement models
Authors: Buhl Camille , Sword Gregory A. , Simpson Stephen J.
Published: August 2012

Wingless locust nymphs can form massive migratory groups known as bands, whose coordinated movement results from local interactions. We analysed the spatial distribution of locusts within naturally occurring bands and compared them with computer simulations to infer which interaction rules are used by individuals. We found that the empirical radial distribution of neighbours around a focal individual was isotropic, indicating a tendency for locusts to interact with neighbours all around them, rather than a bias towards pursuing individuals ahead or escaping from the ones following behind. By using maps of neighbour densities and pair correlation functions, we found evidence for a short-range repulsion force, balanced by a clustering force, presumably alignment and/or attraction, at a distance of around 3 cm. These results were similar to those observed when using a ‘zonal’ self-propelled particles model where repulsion/alignment/attraction forces are delimited by concentric circular zones of set radii. However, the profiles obtained either by using different combinations of forces, limiting the number of neighbours involved in interactions, or by varying the range of some zones, all appeared to produce similar results, thereby limiting the ability to more precisely determine the rules underlying locust interactions.
Different Accumulation of Free Amino Acids during Short- and Long-Term Osmotic Stress in Wheat
Authors: Kovács Zita , Simon-Sarkadi Livia , Vashegyi Ildikó , Kocsy Gábor
Published: August 2012

The effect of wheat chromosome 5A on free amino acid accumulation induced by osmotic stress was compared in chromosome 5A substitution lines with different freezing tolerance. Treatment with 15% polyethylene glycol (PEG) resulted in greater total free amino acid content even after 3 days compared to the controls. The ratio of amino acids belonging to various amino acid families differed after 3-week treatment in the control and PEG-treated plants only in the case of the freezing-sensitive substitution line. There was a transient increase with a maximum after 3 days in the amounts of several amino acids, after which their concentrations exhibited a more gradual increase. During the first days of osmotic stress the Glu, Gln, Asp, Asn, Thr, Ser, Leu, and His concentrations were greater in the tolerant substitution line than in the sensitive one, while the opposite relationship was observed at the end of the PEG treatment. The coordinated changes in the levels of individual amino acids indicated that they are involved in both the short- and long-term responses to osmotic stress. The alterations differed in the two chromosome 5A substitution lines, depending on the stress tolerance of the chromosome donor genotype.
Subjective Outcome Evaluation of the Project P.A.T.H.S. in Different Cohorts of Students
Authors: Shek Daniel T. L. , Ma Cecilia M. S.
Published: August 2012

The project P.A.T.H.S. is an indigenously developed positive youth development program in Hong Kong. In the extension phase (2009/2010 school year), subjective outcome evaluation data were collected from 231 schools involving 89,068 participants after completion of the curricula-based Tier 1 Program. With schools as the units of analysis, results showed that participants generally had positive perceptions of the program content and implementers, with over four-fifth of the participants regarded the program as helpful to them. There were some significant grade differences in the subjective outcome evaluation findings, although the related effect size was not strong. Multiple regression analyses revealed that program content and program implementers predicted perceived effectiveness of the program. The present study suggests that irrespective of cohorts, students in the junior secondary years perceived the program to be beneficial to them.
Cfp1 integrates both CpG content and gene activity for accurate H3K4me3 deposition in embryonic stem cells
Authors: Clouaire Thomas , Webb Shaun , Skene Pete , Illingworth Robert , Kerr Alastair , Andrews Robert , Lee Jeong-Heon , Skalnik David , Bird Adrian
Published: August 2012

Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains the conserved subunit CxxC finger protein 1 (Cfp1), which binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays unanticipated roles in organizing genome-wide H3K4me3 in embryonic stem cells. Cfp1 deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at expressed CGI-associated genes, with minimal consequences for transcription, and creation of “ectopic” H3K4me3 peaks at numerous regulatory regions. DNA binding by Cfp1 was dispensable for targeting H3K4me3 to active genes but was required to prevent ectopic H3K4me3 peaks. The presence of ectopic peaks at enhancers often coincided with increased expression of nearby genes. This suggests that CpG targeting prevents “leakage” of H3K4me3 to inappropriate chromatin compartments. Our results demonstrate that Cfp1 is a specificity factor that integrates multiple signals, including promoter CpG content and gene activity, to regulate genome-wide patterns of H3K4me3.
Eeny meeny miny moe, catch a transcript by the toe, or how to enumerate eukaryotic transcripts: Figure 1.
Authors: Strick Terence R. , Hernandez Nouria
Published: August 2012

In this issue of Genes & Development, Revyakin and colleagues (pp. 1691–1702) measure the relation between individual RNA polymerase II transcription events and transcription factor assembly by counting RNA transcripts retained on the template DNA using single-molecule fluorescence.
Delivery of Recombinant Alphavirus into Hippocampal Slice Tissue Culture
Authors: Lundstrom Kenneth
Published: August 2012

The alphaviruses Semliki Forest virus (SFV) and Sindbis virus (SIN) have been used frequently as expression vectors in vitro and in vivo. Usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. Replication-proficient vectors have also been engineered. Alphaviral vectors can be used as nucleic-acid-based vectors (DNA and RNA) or infectious particles. High-titer viral production is achieved in <2 d. The broad host range of alphaviruses facilitates studies in mammalian and nonmammalian cell lines, primary cells in culture, and in vivo. The strong preference for expression in neuronal cells has made alphaviruses particularly useful in neurobiological studies. Unfortunately, their strong cytotoxic effect on host cells, relatively short-term transient expression patterns, and the reasonably high cost of viral production remain drawbacks. However, novel mutant alphaviruses have shown reduced cytotoxicity and prolonged expression. This protocol describes gene delivery of recombinant alphavirus to hippocampal slice cultures. Organotypic slices are covered by a layer of glial cells that impedes the penetration of viral particles to the neurons. Thus, viral particles should be injected manually into the extracellular space of the tissue.
Automated Lineage and Expression Profiling in Live Caenorhabditis elegans Embryos
Authors: Murray John Isaac , Bao Zhirong
Published: August 2012

Describing gene expression during animal development requires a way to quantitatively measure expression levels with cellular resolution and to describe how expression changes with time. Fluorescent protein reporters make it possible to measure expression dynamics in live cells by time-lapse microscopy, but it can be challenging to identify expressing cells in complex tissues and to compare expression across organisms. This protocol describes how to use automated lineage analysis to identify cells in Caenorhabditis elegans embryos expressing fluorescent reporters and how to quantify that expression with cellular resolution. Because C. elegans develops through an invariant pattern of cell divisions, every cell's identity and future fate can be predicted from its pattern of previous cell divisions. Automated analysis of images collected from embryos expressing a fluorescent histone transgene in all cells allows lineage tracing and cell identification. This provides a scaffold with which to describe expression of a second color reporter such as a fusion of a second fluorescent protein to a gene of interest or its regulatory sequences. These methods can also be used for analysis of reporter expression, cell division timing, and cell position in genetically perturbed embryos. The protocol describes how to prepare C. elegans strains containing nuclear-expressed fluorescent reporters, collect images of appropriate quality from embryos, perform automated lineage analysis, manually edit and curate the lineage, and, finally, extract and display reporter signals.
An open‐label, single‐arm, phase 2 study of single‐agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib
Authors: Vij Ravi , Siegel David S. , Jagannath Sundar , Jakubowiak Andrzej J. , Stewart Alexander Keith , McDonagh Kevin , Bahlis Nizar , Belch Andrew , Kunkel Lori A. , Wear Sandra , Wong Alvin F. , Orlowski Robert Z. , Wang Michael
Published: July 2012

Carfilzomib is a next‐generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open‐label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1–3 prior therapies, including at least one bortezomib‐based regimen, received carfilzomib 20 mg/m2 in a twice‐weekly, consecutive‐day dosing schedule for ≤12 monthly cycles. The best overall response rate (ORR) was 17·1% and the clinical benefit response rate (ORR + minimal response) was 31·4%. The median duration of response was >10·6 months and the median time to progression was 4·6 months. The most common adverse events were fatigue (62·9%), nausea (60·0%), and vomiting (42·9%). No exacerbation of baseline peripheral neuropathy was observed. Single‐agent carfilzomib was generally well tolerated for up to 12 treatment cycles and showed activity in patients with relapsed and/or refractory MM who had received prior treatment with bortezomib. These data, combined with an acceptable toxicity profile, support the potential use of carfilzomib in patients with relapsed and/or refractory MM and warrant continued investigation of carfilzomib as single agent or in combination with other agents.
Microfluidic study of competence regulation in Streptococcus mutans: environmental inputs modulate bimodal and unimodal expression of comX
Authors: Son Minjun , Ahn Sang‐Joon , Guo Qiang , Burne Robert A. , Hagen Stephen J.
Published: July 2012

Streptococcus mutans regulates genetic competence through a complex network that receives inputs from a number of environmental stimuli, including two signalling peptides designated as CSP and XIP. The response of the downstream competence genes to these inputs shows evidence of stochasticity and bistability and has been difficult to interpret. We have used microfluidic, single‐cell methods to study how combinations of extracellular signals shape the response of comX, an alternative sigma factor governing expression of the late competence genes. We find that the composition of the medium determines which extracellular signal (XIP or CSP) can elicit a response from comX and whether that response is unimodal or bimodal across a population of cells. In a chemically defined medium, exogenous CSP does not induce comX, whereas exogenous XIP elicits a comX response from all cells. In complex medium, exogenous XIP does not induce comX, whereas CSP elicits a bimodal comX response from the population. Interestingly, bimodal behaviour required an intact copy of comS, which encodes the precursor of XIP. The comS‐dependent capability for both unimodal and bimodal response suggests that a constituent – most likely peptides – of complex medium interacts with a positive feedback loop in the competence regulatory network.
Association of ICU size and annual case volume of renal replacement therapy patients with mortality
Authors: VAARA S. T. , REINIKAINEN M. , KAUKONEN K. ‐M. , PETTILÄ V. ,   FOR THE FINNISH INTENSIVE CARE CONSORTIUM
Published: July 2012

Background

We aimed to reveal whether the size of an intensive care unit (ICU) or its annual case volume of patients treated with renal replacement therapy (RRT) for acute kidney injury (AKI) is associated with hospital mortality.

Methods

This was a retrospective cohort study in the Finnish Intensive Care Consortium (FICC) database in 2007–2008. We divided the 23 FICC‐member ICUs first into small or large according to ICU size, and second into low, medium, or high‐volume tertiles according to annual case volume of patients with RRT. We compared crude hospital mortality, Simplified Acute Physiology Score (SAPS) II‐, and case‐mix‐adjusted hospital mortality in small vs. large ICUs and in low‐ or medium‐volume vs. high‐volume ICUs.

Results

The median (interquartile range) annual case volume of patients with RRT for AKI per one ICU was 25 (19–45). Patients in small or low‐volume ICUs were older and less severely ill. Crude and SAPS II ‐adjusted hospital mortality rates were significantly higher in small ICUs but not significantly different in case volume tertiles. After adjusting for age, severity of illness, intensity of care, propensity to receive RRT, and day of RRT initiation, treatment in low or medium volume ICUs was associated with an increased risk for hospital mortality.

Conclusions

Crude and adjusted hospital mortality rates of patients treated with RRT for AKI were higher in small ICUs. Patients treated in high‐volume ICUs had a decreased adjusted risk for hospital mortality compared to those in low‐or medium volume ICUs.
Effects of high‐sulphur water on hepatic gene expression of steers fed fibre‐based diets
Authors: Kessler K. L. , Olson K. C. , Wright C. L. , Austin K. J. , McInnerney K. , Johnson P. S. , Cockrum R. R. , Jons A. M. , Cammack K. M.
Published: August 2012

Sulphur‐induced polioencephalomalacia (sPEM), a neurological disorder affecting ruminants, is frequently associated with the consumption of high‐sulphur (S) water and subsequent poor performance. Currently, there is no economical method for S removal from surface water sources, and alternative water sources are typically neither readily available nor cost‐effective. Determination of genes differentially expressed in response to high‐S water consumption may provide a better understanding of the physiology corresponding to high dietary S and ultimately lead to the development of treatment and prevention strategies. The objective of this study was to determine changes in gene expression in the liver, an organ important for S metabolism, of fibre‐fed steers consuming high‐S water. For this study, liver tissues were collected on the final day of a trial from yearling steers randomly assigned to low‐S water control (566 mg/kg SO4;n = 24), high‐S water (3651 mg/kg SO4;n = 24) or high‐S water plus clinoptilolite supplemented at either 2.5% (n = 24) or 5.0% (n = 24) of diet dry matter (DM). Microarray analyses on randomly selected healthy low‐S control (n = 4) and high‐S (n = 4; no clinoptilolite) steers using the Affymetrix GeneChip Bovine Genome Array revealed 488 genes upregulated (p < 0.05) and 154 genes downregulated (p < 0.05) in response to the high‐ vs. low‐S water consumption. Real‐time RT‐PCR confirmed the upregulation (p < 0.10) of seven genes involved in inflammatory response and immune functions. Changes in such genes suggest that ruminant animals administered high‐S water may be undergoing an inflammation or immune response, even if signs of sPEM or compromised health are not readily observed. Further study of these, and other affected genes, may deliver new insights into the physiology underlying the response to high dietary S, ultimately leading to the development of treatments for high S–affected ruminant livestock.
Physiological and hormonal aspects in female domestic pigeons (Columba livia) associated with breeding stage and experience
Authors: Dong X. Y. , Zhang M. , Jia Y. X. , Zou X. T.
Published: August 2012

The present study examined the changes in serum biochemical values, hormone profiles and ovary prolactin receptor (PRLR) gene expression occurring in female domestic pigeons (Columba livia) under different breeding status and experience. The egg‐laying pigeons had lower calcium, total protein, albumin, prolactin levels and higher oestrogen levels than those of incubating birds (p < 0.05). First‐time breeders had higher (p < 0.05) progesterone levels and lower (p < 0.05) prolactin levels than that of experienced ones. The levels of oestrogen and follicle‐stimulating hormone (FSH) increased with age (p < 0.05). The very old birds showed a pronounced increase (p < 0.05) in PRL, FSH and progesterone and a little decrease in oestrogen. Serum prolactin level was not correlated with the ovary PRLR mRNA expression pattern among all the pigeons. Results showed that serum physiological profile of female pigeons was correlated with breeding status, whereas reproductive hormone levels were correlated with advancing breeding experience. It was concluded that female pigeons had a good ability of recovering from nutrient loss after each breeding attempts, and the degradation of reproductive performance might be attributed to changes in the endocrine system.
Oral care practices of intensive care nurses: A descriptive study
Authors: Türk Gülengün , Kocaçal Güler Elem , Eşer İsmet , Khorshid Leyla
Published: July 2012

The aim of this study was to investigate intensive care unit (ICU) nurses’ views and practices on oral care and to define the factors related to oral care measures. A study was carried out in eight ICUs of a teaching hospital in 2008. One hundred one nurses constituted the study sample. The data were collected using ‘Oral Care Practices Survey’ which included demographic characteristics (5 items) and current oral care practices (13 items). Oral care was given the highest priority by nearly 60% of the nurses. The most commonly used solution was sodium bicarbonate (79.2%), and the most frequently used equipment was foam swab (82.2%). Oral care was carried out less than every 4 h per day by 44.5% of the nurses. The oral care products and solutions were reported to be different in almost every unit. The relationship between the use of toothpaste and the place of employment was statistically significant (x2 = 24.566, d.f. = 6, P = 0.000). There was a statistical significance between the clinics and frequency of oral care (x2 = 81.486, d.f. = 42, P = 0.000). This study suggests that there is a wide variety of type and frequency of oral care measures among ICU nurses. Optimal oral care supported by evidence is an effective prevention method for eliminating oral complications.
The effectiveness of therapeutic interventions on quality of life for vitiligo patients: A systematic review
Authors: Chan Moon Fai , Chua Tse Lert
Published: July 2012

This paper reviews the effectiveness of therapeutic interventions on quality of life for adult patients with vitiligo. We systematically searched nine databases from 1990 to February 2010 and reviewed randomized controlled trials and quasi‐experimental studies of current therapeutic interventions for vitiligo, including oral, topical, combination, camouflage, cognitive‐behavioural therapy and grafting. Quality of life outcomes were collected. The Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument was used for quality assessment. Nine studies were included for this review, and all treatments were found to improve quality of life for vitiligo patients. Disease‐altering interventions were effective in improving quality of life. Lifestyle‐altering interventions were found to be selectively effective for patients with more severe quality of life impairment. Current interventions for vitiligo are effective in improving quality of life either by enhancing physical appearance of the patient or by addressing the psychological distress directly. Less effectiveness was achieved for the functional and social dimensions, which are more dependent on social and cultural norms. This suggests that current interventions alone are inadequate to address the holistic quality of life challenges associated with vitiligo.
Nocturnal enuresis
Authors: Harari Michael D
Published: July 2012

Nocturnal enuresis (NE) is increasingly seen as part of a heterogeneous phenomenon that at times will include daytime lower urinary tract symptoms such as urgency, frequency and wetting – with reduced bladder storage, usually due to an overactive bladder. In turn, these may be associated with constipation and/or faecal soiling. This paper discusses these considerations in the management of NE.
Impact of pre‐implant lower urinary tract symptoms on postoperative urinary morbidity after permanent prostate brachytherapy
Authors: Teishima Jun , Iwamoto Hideo , Miyamoto Katsutoshi , Shoji Koichi , Masumoto Hiroshi , Inoue Shogo , Kobayashi Kanao , Kajiwara Mitsuru , Matsubara Akio
Published: August 2012

Objectives:  To assess the impact of baseline lower urinary tract symptoms on postoperative urinary morbidity in patients being treated for prostate cancer with 125‐I permanent prostate brachytherapy.

Methods:  A total of 104 prostate cancer patients were enrolled in this study. Their urinary morbidity was followed up using the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite for 12 months or more after permanent prostate brachytherapy. Patients were classified into two groups based on their baseline International Prostate Symptom Score: the low International Prostate Symptom Score group (score ≤ 7) and the high International Prostate Symptom Score group (score ≥ 8). Urinary morbidity was estimated in each group based on the results of the International Prostate Symptom Score and Expanded Prostate Cancer Index Composite measured before permanent prostate brachytherapy, and at 1, 3, 6, 9 and 12 months after the end of all radiation therapy.

Results:  The overall mean total International Prostate Symptom Score, International Prostate Symptom Score quality of life score, and urinary‐related scores for Expanded Prostate Cancer Index Composite were significantly worse at 1 month after the end of treatment, but they improved gradually after the treatment and recovered to the baseline level within 12 months. Even in the high‐International Prostate Symptom Score group, the International Prostate Symptom Score and International Prostate Symptom Score Quality of Life score were significantly worse at 1–3 months after permanent prostate brachytherapy, and then recovered to the baseline level without prolongation. Although the urination‐related Expanded Prostate Cancer Index Composite score in the high‐International Prostate Symptom Score group was significantly worse at 1 month after permanent prostate brachytherapy in comparison with that in the low‐International Prostate Symptom Score group, it recovered to the baseline level without prolongation.

Conclusions:  The present findings suggest that the presence of lower urinary tract symptoms before implantation does not prolong urinary morbidity after permanent prostate brachytherapy.