bluuebunny/crossref_metadata_2025 huggingface dataset:
Depth-profiling X-ray photoelectron spectroscopy (XPS) analysis of interlayer diffusion in polyelectrolyte multilayers
Authors: Gilbert Jonathan B. , Rubner Michael F. , Cohen Robert E.
Published: April 2013

Functional organic thin films often demand precise control over the nanometer-level structure. Interlayer diffusion of materials may destroy this precise structure; therefore, a better understanding of when interlayer diffusion occurs and how to control it is needed. X-ray photoelectron spectroscopy paired with C
60
+
cluster ion sputtering enables high-resolution analysis of the atomic composition and chemical state of organic thin films with depth. Using this technique, we explore issues common to the polyelectrolyte multilayer field, such as the competition between hydrogen bonding and electrostatic interactions in multilayers, blocking interlayer diffusion of polymers, the exchange of film components with a surrounding solution, and the extent and kinetics of interlayer diffusion. The diffusion coefficient of chitosan (M = ∼100 kDa) in swollen hydrogen-bonded poly(ethylene oxide)/poly(acrylic acid) multilayer films was examined and determined to be 1.4*10
−12
cm
2
/s. Using the high-resolution data, we show that upon chitosan diffusion into the hydrogen-bonded region, poly(ethylene oxide) is displaced from the film. Under the conditions tested, a single layer of poly(allylamine hydrochloride) completely stops chitosan diffusion. We expect our results to enhance the understanding of how to control polyelectrolyte multilayer structure, what chemical compositional changes occur with diffusion, and under what conditions polymers in the film exchange with the solution.
Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation
Authors: Li Baobin , Wang Quan , Pan Xijiang , Fernández de Castro Isabel , Sun Yuna , Guo Yu , Tao Xinwei , Risco Cristina , Sui Sen-Fang , Lou Zhiyong
Published: April 2013

Bunyamwera virus (BUNV), which belongs to the genus
Orthobunyavirus
, is the prototypical virus of the
Bunyaviridae
family. Similar to other negative-sense single-stranded RNA viruses, bunyaviruses possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation and virus replication. The structures of two NPs of members of different genera within the
Bunyaviridae
family have been reported. However, their structures, RNA-binding features, and functions beyond RNA binding significantly differ from one another. Here, we report the crystal structure of the BUNV NP–RNA complex. The polypeptide of the BUNV NP was found to possess a distinct fold among viral NPs. An N-terminal arm and a C-terminal tail were found to interact with neighboring NP protomers to form a tetrameric ring-shaped organization. Each protomer bound a 10-nt RNA molecule, which was acquired from the expression host, in the positively charged crevice between the N and C lobes. Inhomogeneous oligomerization was observed for the recombinant BUNV NP–RNA complex, which was similar to the Rift Valley fever virus NP–RNA complex. This result suggested that the flexibility of one NP protomer with adjacent protomers underlies the BUNV ribonucleoprotein complex (RNP) formation. Electron microscopy revealed that the monomer-sized NP–RNA complex was the building block of the natural BUNV RNP. Combined with previous results indicating that mutagenesis of the interprotomer or protein–RNA interface affects BUNV replication, our structure provides a great potential for understanding the mechanism underlying negative-sense single-stranded RNA RNP formation and enables the development of antiviral therapies targeting BUNV RNP formation.
Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis
Authors: Ishigame Harumichi , Zenewicz Lauren A. , Sanjabi Shomyseh , Licona-Limón Paula , Nakayama Maki , Leonard Warren J. , Flavell Richard A.
Published: April 2013

TGF-β signaling in T cells is critical for peripheral T-cell tolerance by regulating effector CD4
+
T helper (Th) cell differentiation. However, it is still controversial to what extent TGF-β signaling in Foxp3
+
regulatory T (Treg) cells contributes to immune homeostasis. Here we showed that abrogation of TGF-β signaling in thymic T cells led to rapid type 1 diabetes (T1D) development in NOD mice transgenic for the BDC2.5 T-cell receptor. Disease development in these mice was associated with increased peripheral Th1 cells, whereas Th17 cells and Foxp3
+
Treg cells were reduced. Blocking of IFN-γ signaling alone completely suppressed diabetes development in these mice, indicating a critical role of Th1 cells in this model. Furthermore, deletion of TGF-β signaling in peripheral effector CD4
+
T cells, but not Treg cells, also resulted in rapid T1D development, suggesting that conventional CD4
+
T cells are the main targets of TGF-β to suppress T1D. TGF-β signaling was dispensable for Treg cell function, development, and maintenance, but excessive IFN-γ production due to the absence of TGF-β signaling in naive CD4
+
T cells indirectly caused dysregulated Treg cell homeostasis. We further showed that T cell–derived TGF-β1 was critical for suppression of Th1 cell differentiation and T1D development. These results indicate that autocrine/paracrine TGF-β signaling in diabetogenic CD4
+
T cells, but not Treg cells, is essential for controlling T1D development.
Melanocortin-4 receptor mutations paradoxically reduce preference for palatable foods
Authors: Panaro Brandon L. , Cone Roger D.
Published: April 2013

Haploinsufficiency of the melanocortin-4 receptor (MC4R) results in melanocortin obesity syndrome, the most common monogenic cause of severe early onset obesity in humans. The syndrome, which produces measurable hyperphagia, has focused attention on the role of MC4R in feeding behavior and macronutrient intake. Studies show that inhibition of MC4R signaling can acutely increase the consumption of high-fat foods. The current study examines the chronic feeding preferences of mice with deletion of one or both alleles of the MC4R to model the human syndrome. Using two-choice diet paradigms with high-fat or high-carbohydrate foods alongside normal chow, we show, paradoxically, that deletion of one allele has no effect, whereas deletion of both alleles of the MC4R actually decreases preference for palatable high-fat and high-sucrose foods, compared with wild-type mice. Nonetheless, we observed hyperphagic behavior from increased consumption of the low-fat standard chow when either heterozygous or homozygous mutant animals were presented with dietary variety. Thus, decreased MC4R signaling in melanocortin obesity syndrome consistently yields hyperphagia irrespective of the foods provided, but the hyperphagia appears driven by variety and/or novelty, rather than by a preference for high-fat or high-carbohydrate foodstuffs.
Teaching and Assessing Residents’ Skills in Managing Heroin Addiction with Objective Structured Clinical Examinations (OSCEs)
Authors: Parish Sharon J. , Stein Melissa R. , Hahn Steven R. , Goldberg Uri , Arnsten Julia H.
Published: April 2013

Background

Heroin-abusing patients present a significant challenge. Objective Structured Clinical Examinations (OSCEs) allow evaluation of residents’ clinical skills. The objective of this study was to examine residents’ OSCE performance assessing and managing heroin abuse.

Methods

Evaluation and comparison of heroin-specific communication, assessment, and management skills in a 5-station postgraduate year 3 (PGY3) substance abuse OSCE. Faculty used a 4-point Likert scale to assess residents’ skills; standardized patients provided written comments.

Results

Two hundred sixty-five internal and family medicine residents in an urban university hospital participated over 5 years. In the heroin station, residents’ skills were better ( P < .001 for both comparisons) in communication (mean overall score: 316 ± 0.51) than in either assessment (mean overall score: 2.66 ± 0.60) or management (mean overall score: 2.50 ± 0.73). The mean score for assessing specific high-risk behaviors was lower than the mean overall assessment score (222 ± 1.01 vs. 2.74 ± .59; P < .0001), and the mean score for recommending appropriate harm reduction management strategies was lower than the mean overall management score (2.39 ± .89 vs. 2.54 ± .74; P < .005). Standardized patients’ comments reflected similar weaknessess in residents’ skills.

Conclusions

Assessment and management of heroin abuse were more challenging for residents than general communication. Additional training is required for residents to assess and counsel patients about high-risk behaviors.
A TPR domain–containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B
Authors: Nijenhuis Wilco , von Castelmur Eleonore , Littler Dene , De Marco Valeria , Tromer Eelco , Vleugel Mathijs , van Osch Maria H.J. , Snel Berend , Perrakis Anastassis , Kops Geert J.P.L.
Published: April 2013

The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B–dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.
A solid-state control system for dynein-based ciliary/flagellar motility
Authors: King Stephen M.
Published: April 2013

Ciliary and flagellar beating requires the coordinated action of multiple dyneins with different enzymatic and motor properties. In this issue, Yamamoto et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201211048) identify the MIA (modifier of inner arms) complex within the Chlamydomonas reinhardtii axoneme that physically links to a known regulatory structure and provides a signaling conduit from the radial spokes to an inner arm dynein essential for waveform determination.
Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation
Authors: Cohn Lillian , Chatterjee Bithi , Esselborn Filipp , Smed-Sörensen Anna , Nakamura Norihiro , Chalouni Cécile , Lee Byoung-Chul , Vandlen Richard , Keler Tibor , Lauer Peter , Brockstedt Dirk , Mellman Ira , Delamarre Lélia
Published: April 2013

Human BDCA3+ dendritic cells (DCs), the proposed equivalent to mouse CD8α+ DCs, are widely thought to cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for cross presentation or a generally enhanced ability to present antigens on MHCI. We compared presentation by BDCA3+ DCs with BDCA1+ DCs using a quantitative approach whereby antigens were targeted to distinct intracellular compartments by receptor-mediated internalization. As expected, BDCA3+ DCs were superior at cross presentation of antigens delivered to late endosomes and lysosomes by uptake of anti-DEC205 antibody conjugated to antigen. This difference may reflect a greater efficiency of antigen escape from BDCA3+ DC lysosomes. In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1+ DCs were as efficient at cross presentation as BDCA3+ DCs. Because BDCA3+ DCs and BDCA1+ DCs were also equivalent at presenting peptides and endogenously synthesized antigens, BDCA3+ DCs are not likely to possess mechanisms for cross presentation that are specific to this subset. Thus, multiple DC populations may be comparably effective at presenting exogenous antigens to CD8+ T cells as long as the antigen is delivered to early endocytic compartments.
Saving Costs through the Decontamination of the Packaging of Unused Medical Supplies Using Hydrogen Peroxide Vapor
Authors: Otter Jonathan A. , Nowakowski Elaine , Salkeld James A. G. , Duclos Mike , Passaretti Catherine L. , Yezli Saber , Ross Tracy , Carroll Karen C. , Perl Trish M.
Published: April 2013

Objective.

Individually packaged sterile supply items may become contaminated and act as vectors for nosocomial transmission of multidrug-resistant organisms (MDROs). Thus, many hospitals have a policy to dispose of these unused, packaged supply items at patient discharge from the hospital, which has considerable cost implications. We evaluated the frequency of contamination of these items, the efficacy of hydrogen peroxide vapor (HPV) in disinfecting them, and costs associated with discarded supplies.

Design.

Before-after study.

Methods.

A pilot study was performed in the rooms of 20 patients known to be colonized or infected with vancomycin-resistant enterococci (VRE), and a follow-up study was performed in an additional 20 rooms of patients under precautions for various MDROs in 6 high-risk units. Five pairs of supply items were selected. One item of each pair was sampled without exposure to HPV, and the other was sampled after HPV exposure. The cost of discarded supplies was calculated by examining stock lists of supplies stored on the study units.

Results.

Seven (7%) of 100 items were contaminated with VRE in the pilot study, and 9 (9%) of 100 items were contaminated with MDROs in the follow-up study. None of the items were contaminated after exposure to HPV (P < .02 in both the pilot and the follow-up study). The annual cost of supplies discarded at patient hospital discharge was $387,055. This figure does not include the cost of waste disposal and is therefore likely to be an underestimation of the financial burden.

Conclusions.

HPV effectively disinfected the packaging of supply items, which could generate considerable financial and environmental benefits.
Evaluation of a New Hydrogen Peroxide Wipe Disinfectant
Authors: Boyce John M. , Havill Nancy L.
Published: April 2013

A new activated hydrogen peroxide wipe disinfectant was used to disinfect 10 high-touch surfaces in 72 patient rooms. After cleaning, 99% of surfaces yielded less than 2.5 colony-forming units/cm2, 75% yielded no growth, and 70% yielded adenosine triphosphate counts of less than 250 relative light units. The new disinfectant was highly effective.
Capability Brown, the Aristocracy, and the Cultivation of the Eighteenth-Century British Landscaping Industry
Authors: Wild Andrew M.
Published: April 2013

Capability Brown cannot be identified as the originator of modern landscaping, yet he created a business that achieved an unrivaled impact, outshining those before, during, and after his lifetime. Whether Brown was a great artist, opinions may differ. However, there is evidence that Brown was an outstandingly successful businessman. From humble origins, Brown ultimately created a business that seized the lion’s share of the landscaping market of Britain’s elite in the second half of the eighteenth century, counting half of the House of Lords as his clients. A study of Brown’s surviving account book, bank ledgers, and personal correspondence provides new insight into the rapid development, vast scale, and nature of his business. This research shows that commissions were not just gained due to his skills in landscaping, but through his exceptional business acumen, his method of operations, organizational structure, focus, work ethic, and ability to develop contacts and win trust with both the aristocracy and ultimately the King of England. What emerges is a picture of Brown as an entrepreneur of considerable skill, enabling him to uniquely build a national landscaping business.
Long‐term pattern of brain natriuretic peptide and N‐terminal pro brain natriuretic peptide and its determinants in the general population: contribution of age, gender, and cardiac and extra‐cardiac factors
Authors: Luchner Andreas , Behrens Gundula , Stritzke Jan , Markus Marcello , Stark Klaus , Peters Annette , Meisinger Christa , Leitzmann Michael , Hense Hans‐Werner , Schunkert Heribert , Heid Iris M.
Published: April 2013

Aims

The natriuretic peptides BNP and NT‐proBNP are potent cardiac markers, but knowledge of long‐term changes is sparse. We thus quantified determinants of change in BNP and NT‐proBNP in a study of south German residents (KORA).

Methods and results

A total of 1005 men and women (age 25–74 years, mean 48 years) underwent physical examination and echocardiography at baseline and at follow‐up after 10 years. The current analysis comprised 877 subjects with dual measurements of BNP and NT‐proBNP. Both markers increased in both sexes (P< 0.001) during the 10‐year follow‐up, and higher levels in women persisted across time (Pfor sex difference <0.001). Among baseline covariates, predictors for 10‐year change of NT‐proBNP, BNP, or both were age, sex, diabetes status, and heart rate (multivariable regression analysis, eachP< 0.05). However, changes of covariates over the 10‐year follow‐up were much stronger determinants. Specifically, incident myocardial infarction, new beta‐blocker medication, and increased cardiac parameters (left atrial diameter, LV end‐diastolic diameter, and LV mass index) were associated with increasing BNP, NT‐proBNP, or both, whereas increased heart rate, haematocrit, and body mass index (BMI) were associated with decreasing BNP and NT‐proBNP (allP< 0.05).

Conclusion

Next to ageing and sex, a variety of changes in covariates reflecting the sequelae of cardiac remodelling as well as myocardial infarction and diabetes influence long‐term changes of BNP and NT‐proBNP. Of note, diabetes and increased BMI exert opposite effects. For interpretation of individual marker concentrations, a host of covariates needs to be considered, especially in subjects without prevalent or incident cardiac disease.
Evidence for secular evolution of disc structural parameters in massive barred galaxies
Authors: Sánchez-Janssen Rubén , Gadotti Dimitri A.
Published: April 2013

We address the effects of bar-driven secular evolution in discs by comparing their properties in a sample of nearly 700 unbarred and barred (42 ± 3 per cent of the population) massive disc galaxies (M⋆ ≥ 1010 M⊙). We make use of accurate structural parameters derived from i-band bulge/disc/bar decompositions to show that, as a population, barred discs tend to have fainter central surface brightness (Δμ0 ≈ 0.25 mag), and disc scalelengths that are ≈15 per cent larger than those of unbarred galaxies of the same stellar mass. The corresponding distributions of μ0 and h are statistically inconsistent at the 5.2σ and 3.8σ levels, respectively. Bars rarely occur in high-surface brightness discs, with less than 5 per cent of the barred population having μ0 < 19.5 mag arcsec−2 – compared to 20 per cent for unbarred galaxies. They tend to reside in moderately blue discs, with a bar fraction that peaks at (g − i)disc ≈ 0.95 mag and mildly declines for both bluer and redder colours. These results demonstrate noticeable structural differences between the discs of barred and unbarred galaxies, which we argue are the result of bar-driven evolution – in qualitative agreement with longstanding theoretical expectations.
Development and Validation of a Score for Prediction of Postoperative Respiratory Complications
Authors: Brueckmann Britta , Villa-Uribe Jose L. , Bateman Brian T. , Grosse-Sundrup Martina , Hess Dean R. , Schlett Christopher L. , Eikermann Matthias
Published: April 2013

Background:

Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care.

Methods:

Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated.

Results:

In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their β coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55–1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation.

Conclusion:

The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications.
Social niche specialization under constraints: personality, social interactions and environmental heterogeneity
Authors: Montiglio Pierre-Olivier , Ferrari Caterina , Réale Denis
Published: April 2013

Several personality traits are mainly expressed in a social context, and others, which are not restricted to a social context, can be affected by the social interactions with conspecifics. In this paper, we focus on the recently proposed hypothesis that social niche specialization (i.e. individuals in a population occupy different social roles) can explain the maintenance of individual differences in personality. We first present ecological and social niche specialization hypotheses. In particular, we show how niche specialization can be quantified and highlight the link between personality differences and social niche specialization. We then review some ecological factors (e.g. competition and environmental heterogeneity) and the social mechanisms (e.g. frequency-dependent, state-dependent and social awareness) that may be associated with the evolution of social niche specialization and personality differences. Finally, we present a conceptual model and methods to quantify the contribution of ecological factors and social mechanisms to the dynamics between personality and social roles. In doing so, we suggest a series of research objectives to help empirical advances in this research area. Throughout this paper, we highlight empirical studies of social niche specialization in mammals, where available.
Yellow-bellied marmots: insights from an emergent view of sociality
Authors: Blumstein Daniel T.
Published: April 2013

Ecological factors explain variation in sociality both within and between species of marmots—large alpine ground squirrels. Fifty years of study, by me and my colleagues, of the yellow-bellied marmots (Marmota flaviventris) at the Rocky Mountain Biological Laboratory, near Crested Butte, CO, USA, has created opportunities to see how sociality changes with population and group size. Over the past decades, we have witnessed a natural experiment whereby the population tripled in size. If we view sociality as an emergent process, then demography acts as a constraint on interactions between individuals, and the threefold increase in population size should have consequences for group structure. We have used social network statistics to study the causes and consequences of social interactions by capitalizing on this demographic variation. Such an emergent view is ideally studied in an integrative Tinbergian way that focuses on both mechanism and function. We have determined that some social attributes are heritable, that social cohesion is established through age and kin structure, that well-embedded females (but not males) are less likely to disperse, and that there are fitness consequences of social attributes. Together, this integrative relationship-centred view expands on the traditional ecological model of sociality and offers a framework that can be applied to other systems.
Country-specific antibiotic use practices impact the human gut resistome
Authors: Forslund Kristoffer , Sunagawa Shinichi , Kultima Jens Roat , Mende Daniel R. , Arumugam Manimozhiyan , Typas Athanasios , Bork Peer
Published: April 2013

Despite increasing concerns over inappropriate use of antibiotics in medicine and food production, population-level resistance transfer into the human gut microbiota has not been demonstrated beyond individual case studies. To determine the “antibiotic resistance potential” for entire microbial communities, we employ metagenomic data and quantify the totality of known resistance genes in each community (its resistome) for 68 classes and subclasses of antibiotics. In 252 fecal metagenomes from three countries, we show that the most abundant resistance determinants are those for antibiotics also used in animals and for antibiotics that have been available longer. Resistance genes are also more abundant in samples from Spain, Italy, and France than from Denmark, the United States, or Japan. Where comparable country-level data on antibiotic use in both humans and animals are available, differences in these statistics match the observed resistance potential differences. The results are robust over time as the antibiotic resistance determinants of individuals persist in the human gut flora for at least a year.
Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation
Authors: Kao Yu‐Hsun , Chen Yao‐Chang , Chung Chen‐Chih , Lien Gi‐Shih , Chen Shih‐Ann , Kuo Ching‐Chuan , Chen Yi‐Jen
Published: April 2013

Heart failure (HF) can increase atrial fibrillation and induce cardiac hypermethylation. The homeobox gene Pitx2c plays important roles in the genesis of atrial fibrillation and the promoter region of Pitx2c contains cytosine–phosphate–guanine islands. Therefore, epigenetic modification by hypermethylation may reduce Pitx2c expression in atrial myocytes. The aim of the present study were to evaluate whether HF can modulate DNA methylation of Pitx2c and the potential mechanisms involved.

We used real‐time polymerase chain reaction, immunoblotting and pyrosequencing to investigate RNA and protein expression, as well as the methylation of Pitx2c, in isoproterenol‐induced HF, healthy rat left atria and in HL‐1 cells with and without (control) exposure to angiotensin (Ang) II (0.1 and 1 μmol/L) or isoproterenol (1 or 10 μmol/L) for 24 h.

The HF atrium exhibited increased Pitx2c promoter methylation with increased DNA methyltransferase (DNMT) 1 and decreased Pitx2c protein levels compared with the normal atrium. Angiotensin II (0.1 and 1 μmol/L), increased Pitx2c promoter methylation in HL‐1 cells with increased DNMT1 and decreased Pitx2c and Kir2.1 protein levels compared with control cells. These effects were attenuated by the methylation inhibitor 5‐aza‐2′‐deoxycytidine (0.1 μmol/L) and by the AngII receptor blocker losartan (10 μmol/L). However, isoproterenol (1 and 10 μmol/L) did not change the expression of the Pitx2c, DNMT1 and Kir2.1 proteins.

In conclusion, HF induces Pitx2c promoter hypermethylation and AngII may contribute to the hypermethylation in HF.
Clitic Doubling in Vernacular Medieval Greek
Authors: Soltic Jorie
Published: April 2013

This paper provides the first in‐depth study of clitic doubling in vernacular Medieval Greek. First, it is shown that the four‐part typology (topicalization; right‐dislocation; backgrounding; left‐dislocation) recently developed on the basis of Modern Greek is perfectly applicable to vernacular Medieval Greek. Moreover, clitic doubling serves the same pragmatic function in Medieval Greek as in many modern spoken languages: it marks an object as the topic of the utterance (as opposed to the focus). For this purpose, the notion of ‘topic’ is clearly defined and distinguished from the concept of (referential) ‘givenness’. Special attention is paid to the distribution of the clitic pronouns, as their position is diagnostic for the topic/focus distinction. Innovatively, the frequent occurrence of clitic doubling in my corpus is associated with the oral discourse which the vernacular texts are acknowledged to adopt. In this regard, two other constructions are discussed: dislocated genitives and dislocated subjects.
Taxonomic review of the familyIbaliidae (Cynipoidea:Hymenoptera) fromKorea
Authors: Choi Won‐Young , Lee Jong‐Wook , Suh Kyong‐In
Published: April 2013

The familyIbaliidae of the orderHymenoptera inKorea is reviewed. Previously, only one species,Ibalia takachihoihas been recorded in theKorean fauna. In this study, we report three ibaliid species,Ibalia(Ibalia)leucospoides leucospoides,Ibalia(Tremibalia)japonica andIbalia (Tremibalia) ornata, new toKorean fauna. A key toKorean ibaliid species, redescriptions and illustrations of diagnostic characters are given.
Loss of the Birt–Hogg–Dubé gene product folliculin induces longevity in a hypoxia‐inducible factor–dependent manner
Authors: Gharbi Hakam , Fabretti Francesca , Bharill Puneet , Rinschen Markus M. , Brinkkötter Sibylle , Frommolt Peter , Burst Volker , Schermer Bernhard , Benzing Thomas , Müller Roman‐Ulrich
Published: April 2013

Signaling through the hypoxia‐inducible factor hif‐1 controls longevity, metabolism, and stress resistance in Caenorhabditis elegans. Hypoxia‐inducible factor (HIF) protein levels are regulated through an evolutionarily conserved ubiquitin ligase complex. Mutations in the VHL gene, encoding a core component of this complex, cause a multitumor syndrome and renal cell carcinoma in humans. In the nematode, deficiency in vhl‐1 promotes longevity mediated through HIF‐1 stabilization. However, this longevity assurance pathway is not yet understood. Here, we identify folliculin (FLCN) as a novel interactor of the hif‐1/vhl‐1 longevity pathway. FLCN mutations cause Birt–Hogg–Dubé syndrome in humans, another tumor syndrome with renal tumorigenesis reminiscent of the VHL disease. Loss of the C. elegans ortholog of FLCN F22D3.2 significantly increased lifespan and enhanced stress resistance in a hif‐1‐dependent manner. F22D3.2, vhl‐1, and hif‐1 control longevity by a mechanism distinct from insulin‐like signaling. Daf‐16 deficiency did not abrogate the increase in lifespan mediated by flcn‐1. These findings define FLCN as a player in HIF‐dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma.
Chest radiography of acute paediatric lower respiratory infections: experience versus interobserver variation
Authors: Levinsky Yoel , Mimouni Francis B , Fisher Drora , Ehrlichman Matityahu
Published: April 2013

Aim

To determine radiological and clinical chest radiographs (CRs) interpretation agreement in children with acute respiratory disease (ARD) versus clinical experience in multiple observers.

Methods

Chest radiographs obtained in 70 consecutive children at the emergency department in 2010–2011 for ARD were reviewed. They were interpreted by 1–10 paediatric residents, three board‐certified paediatricians (BCPs), three paediatric pulmonologists and one paediatric radiologist. Chest radiographs were analysed for presence of 10 radiological features and five diagnoses. A short clinical and laboratory context was given. Each child was given a clinical decision. Statistical analysis was by Fleiss’ kappa for multiple observers.

Results

Kappas by selected major diagnostic features and by observer experience were expressed relative to diagnosis by paediatric radiologist. Best agreements were for pleural effusion and pneumonia and worst for normal X‐ray, hyperinflation and atelectasis. Years of experience were influential. Antibiotics for pneumonia diagnosed by radiologist would not have been prescribed in 23% of cases by residents, 25% by BCPs and 15% by pulmonologists.

Conclusion

In ARD in children, there is little interobserver agreement, especially among residents, which may impact on major clinical decision. There is a need to systematically train physicians in CRs reading.
Systematic review: macrophage activation syndrome in inflammatory bowel disease
Authors: Fries W. , Cottone M. , Cascio A.
Published: April 2013

Background

Recently, there have been increasingly frequent reports on the occurrence of macrophage activation syndrome (MAS) in patients with inflammatory bowel disease (IBD). Clinically, MAS is characterized mainly by fever, hepatosplenomegaly, cytopenia, and elevated circulating ferritin and CD25. Mortality, even if diagnosed rapidly, is high.

Aim

To identify all reports on MAS in IBD and to establish data on triggering agents, immunosuppression leading to MAS, and mortality.

Methods

A language unrestricted search on Pubmed and Scopus relating to the past 30 years was carried out by matching the following search‐terms: h(a)emophagocytic lymphohistiocytosis OR h(a)emophagocytic lymphohistiocytic syndrome OR macrophage activation syndrome OR opportunistic infections OR cytomegalovirus OR Epstein‐Barr virus AND Crohn's disease OR ulcerative colitis OR inflammatory bowel disease(s).

Results

Fifty cases were identified with an overall mortality of 30%. Virus‐related MAS associated with cytomegalovirus or Epstein‐Barr virus infections represents the main type of MAS, but in isolated cases bacterial infections precipitated the syndrome. In four cases (8%), a lymphoma was present at the time of MAS diagnosis or developed shortly thereafter. Thiopurine monotherapy was given before MAS onset in 56% of the patients, whereas multiple immunosuppression, including biologics, was administered to 24%.

Conclusions

In IBD patients, the syndrome appears to be triggered by infections, but genetic susceptibility may contribute to its development. Since immunosuppressive therapy represents the backbone of therapeutic interventions in IBD, with the risk of new, or the reactivation of latent infections, even more frequent cases of macrophage activation syndrome may be expected.
Increased expression of the transient receptor potential cation channel 6 gene in patients with primary open‐angle glaucoma
Authors: Chen Shida , Fan Qian , Gao Xinbo , Wang Xiaolei , Huang Rui , Laties Alan M , Zhang Xiulan
Published: April 2013

Background

The result of primary open‐angle glaucoma is the loss of retinal ganglion cells. Transient receptor potential cation channel 6 is a pressure‐related channel that may function in the survival of retinal ganglion cells. The purpose of this study was to evaluate the expression levels of the transient receptor potential cation channel 6 gene in patients with primary open‐angle glaucoma.

Design

Randomization study at Zhongshan Ophthalmic Center in China.

Participants

80 primary open‐angle glaucoma patients and 75 cataract patients recruited from Zhongshan Ophthalmic Center.

Methods

Total RNA was extracted from the leukocytes of the peripheral blood collected. The levels of transient receptor potential cation channel 6–messenger RNA were determined by real‐time polymerase chain reaction. Related factors including age, intraocular pressure, optic cup‐to‐disc ratio and visual field defect were analysed accordingly.

Main Outcome Measures

Clinical examination and the messenger RNA level.

Results

The expression level of the transient receptor potential cation channel 6 gene in the leukocytes of primary open‐angle glaucoma patients was two times higher when compared with control cataract patients. The gene expression level was also correlated with intraocular pressure and cup‐to‐disc ratio. Treatment with different anti‐glaucoma drugs did not affect the gene expression.

Conclusions

Increasing expression levels of the transient receptor potential cation channel 6 gene in the blood accompanies chronic elevation of intraocular pressure in primary open‐angle glaucoma and may serve as a genetic biomarker for primary open‐angle glaucoma.
Validity of a new optic disc grading software for use in clinical and epidemiological research
Authors: Tham Yih‐Chung , Cheung Carol Y , Wong Tien Y , Baskaran Mani , Liu Jiang , Lee Beng‐Hai , Yin Fengshou , Wong Damon WK , Wang Jie Jin , Mitchell Paul , Aung Tin , Cheng Ching‐Yu
Published: April 2013

Background

To determine the reliability and agreement of a new optic disc grading software program for use in clinical, epidemiological research.

Design

Reliability and agreement study.

Samples

328 monoscopic and 85 stereoscopic optic disc images.

Methods

Optic disc parameters were measured using a new optic disc grading software (Singapore Optic Disc Assessment) that is based on polynomial curve‐fitting algorithm. Two graders independently graded 328 monoscopic images to determine intergrader reliability. One grader regraded the images after 1 month to determine intragrader reliability. In addition, 85 stereo optic disc images were separately selected, and vertical cup‐to‐disc ratios were measured using both the new software and standardized Wisconsin manual stereo‐grading method by the same grader 1 month apart. Intraclass correlation coefficient (ICC) and Bland–Altman plot analyses were performed.

Main Outcome Measures

Optic disc parameters.

Results

The intragrader and intergrader reliability for optic disc measurements using Singapore Optic Disc Assessment was high (ICC ranging from 0.82 to 0.94). The mean differences (95% limits of agreement) for intergrader vertical cup‐to‐disc ratio measurements were 0.00 (−0.12 to 0.13) and 0.03 (−0.15 to 0.09), respectively. The vertical cup‐to‐disc ratio agreement between the software and Wisconsin grading method was extremely close (ICC = 0.94). The mean difference (95% limits of agreement) of vertical cup‐to‐disc ratio measurement between the two methods was 0.03 (−0.09 to 0.16).

Conclusions

Intragrader and intergrader reliability using Singapore Optic Disc Assessment was excellent. This software was highly comparable with standardized stereo‐grading method. Singapore Optic Disc Assessment is useful for grading digital optic disc images in clinical, population‐based studies.
Comparison between intraoral indirect and conventional film‐based imaging for the detection of dental root fractures: an ex vivo study
Authors: Shintaku Werner H. , Venturin Jaqueline S. , Noujeim Marcel , Dove Stephen B.
Published: April 2013

Digital intraoral radiographic systems have been rapidly replacing conventional dental X‐ray films for diagnosis of dental diseases. Current scientific literature supports the use of these digital systems for the detection of dental caries, periodontal bone loss, and periapical pathologies. However, relatively few studies have been published addressing the detection of dental root fractures. The purpose of this study was to compare the intraoral F‐speed film (Insight) with two photostimulable phosphor (PSP) indirect digital systems (ScanX and Digora Optime) for the detection of simulated dental root fractures. Ten raters evaluated images acquired from 10 dry human cadaver mandibles under optimal viewing conditions. These data were analyzed by a 5‐point receiver operating characteristic curve analysis for statistical differences. Sensitivity and specificity of these systems were also assessed. Since statistically significant difference between the systems was not observed, the results of this study agreeably support indirect digital PSP plates as an alternative to the evaluated conventional film for the detection of dental root fractures.
Oral pathologies of the Neolithic Iceman, c.3,300 bc
Authors: Seiler Roger , Spielman Andrew I , Zink Albert , Rühli Frank
Published: April 2013

The famous Iceman ‘Ötzi’ (South Tyrol Museum of Archaeology, Bolzano, Italy), a Neolithic human ice mummy, offers a unique opportunity to study evolutionary aspects of oral disease. The aim of this study was to assess, for the very first time, his oral cavity, which surprisingly had never been examined systematically. Based on several computed tomography (CT) scans from 1991 onwards and on macroscopic investigation, only a few findings, such as a central maxillary diastema, heavy abrasions, and missing wisdom teeth, were known. We re‐evaluated the latest CT scans from 2005 and found various oral pathologies. In line with the increase of tooth decay in the Neolithic – because of diet change in this historic transition phase – several carious lesions were found, one of which penetrated into the dental pulp. In accordance with the Iceman's troubled life, as several injuries on his body and his violent death attest, mechanical trauma of one of his upper front teeth is evident. Finally, the poor periodontal condition of the Iceman's dentition (e.g. loss of alveolar bone), indicative of periodontitis, was assessed. These oral pathological findings in the Iceman's dentition provide a unique glimpse into the evolutionary history of oral conditions.
Net land‐atmosphere flows of biogenic carbon related to bioenergy: towards an understanding of systemic feedbacks
Authors: Haberl Helmut
Published: April 2013

The notion that biomass combustion is carbon neutral vis‐a‐vis the atmosphere because carbon released during biomass combustion is absorbed during plant regrowth is inherent in the greenhouse gas accounting rules in many regulations and conventions. But this ‘carbon neutrality’ assumption of bioenergy is an oversimplification that can result in major flaws in emission accounting; it may even result in policies that increase, instead of reduce, overall greenhouse gas emissions. This commentary discusses the systemic feedbacks and ecosystem succession/land‐use history issues ignored by the carbon neutrality assumption. Based on recent literature, three cases are elaborated which show that the C balance of bioenergy may range from highly beneficial to strongly detrimental, depending on the plants grown, the land used (including its land‐use history) as well as the fossil energy replaced. The article concludes by proposing the concept of GHG cost curves of bioenergy as a means for optimizing the climate benefits of bioenergy policies.
Heterogeneity in the Relationship between Happiness and Age: Evidence from the German Socio-Economic Panel
Authors: Baetschmann Gregori
Published: April 2013

This paper studies the evolution of life satisfaction over the life course in Germany. It clarifies the causal interpretation of the econometric model by discussing the choice of control variables and the underidentification between age, cohort and time effects. The empirical part analyzes the distribution of life satisfaction over the life course at the aggregated, subgroup and individual level. To the findings: On average, life satisfaction is mildly decreasing up to age 55 followed by a hump shape with a maximum at 70. The analysis at the lower levels suggests that people differ in their life satisfaction trends, whereas the hump shape after age 55 is robust. No important differences between men and women are found. In contrast, education groups differ in their trends: highly educated people become happier over the life cycle, where life satisfaction decreases for less-educated people.
Association of interferon‐alpha gene polymorphisms with chronic hepatitis B virus infection
Authors: Kimkong I. , Tangkijvanich P. , Hirankarn N.
Published: April 2013

In this study, the association between the risk of chronic hepatitis B virus infection and the polymorphisms within promoter regions of IFN‐α1 and five genes was explored. This association study was performed on 180 Thai patients with chronic HBV infection [hepatocellular carcinoma (HCC) = 65 and non‐HCC = 115], 173 individuals with self‐limited HBV infection and 140 healthy controls. Our results showed that the A allele of ‐1823G/A SNP within IFNA1 gene was significantly associated with an increased risk of chronic HBV infection as compared to healthy individuals and self‐limited HBV group [OR (95% CI) = 2.20 (1.51–3.19), P = 0.000014 and OR (95% CI) = 1.61 (1.12–2.33), P = 0.0073, respectively]. The effect of A allele was similar to autosomal recessive in which the presence of AA genotype when compared to GG and GA conferred the OR of 2.79 (95% CI = 1.72–4.52, P = 0.0000085). By multifactor dimensionality reduction analysis, we found the interaction between IFNA5 (‐2529) and IFNA1 (‐1823) genes that gave the risk to chronic HBV infection, with the OR (95% CI) of the high‐risk to low‐risk group was 2.79 (1.77–4.40), P < 0.0001. However, further study in functional significance is required.
TGR5 signalling inhibits the production of pro‐inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease
Authors: Yoneno Kazuaki , Hisamatsu Tadakazu , Shimamura Katsuyoshi , Kamada Nobuhiko , Ichikawa Riko , Kitazume Mina T. , Mori Maiko , Uo Michihide , Namikawa Yuka , Matsuoka Katsuyoshi , Sato Toshiro , Koganei Kazutaka , Sugita Akira , Kanai Takanori , Hibi Toshifumi
Published: April 2013

Bile acids (BAs) play important roles not only in lipid metabolism, but also in signal transduction. TGR5, a transmembrane receptor of BAs, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how BAs operate in immunological responses via the TGR5 pathway in human mononuclear cell lineages. We examined TGR5 expression in human peripheral blood monocytes, several types of in vitro differentiated macrophages (Mϕs) and dendritic cells. Mϕs differentiated with macrophage colony‐stimulating factor and interferon‐γ (Mγ‐Mϕs), which are similar to the human intestinal lamina propria CD14+ Mϕs that contribute to Crohn's disease (CD) pathogenesis by production of pro‐inflammatory cytokines, highly expressed TGR5 compared with any other type of differentiated Mϕ and dendritic cells. We also showed that a TGR5 agonist and two types of BAs, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor‐α production in Mγ‐Mϕs stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the TGR5–cAMP pathway to induce phosphorylation of c‐Fos that regulated nuclear factor‐κB p65 activation. Next, we analysed TGR5 levels in lamina propria mononuclear cells (LPMCs) obtained from the intestinal mucosa of patients with CD. Compared with non‐inflammatory bowel disease, inflamed CD LPMCs contained more TGR5 transcripts. Among LPMCs, isolated CD14+ intestinal Mϕs from patients with CD expressed TGR5. In isolated intestinal CD14+ Mϕs, a TGR5 agonist could inhibit tumour necrosis factor‐α production. These results indicate that TGR5 signalling may have the potential to modulate immune responses in inflammatory bowel disease.
Benefit dependency: The pros and cons of using “caseload” data for national and international comparisons
Authors: De Deken Johan , Clasen Jochen
Published: April 2013

Policy‐makers in advanced welfare states have increasingly expressed concerns over large numbers of working‐age people claiming social security support. Accordingly, policies aimed at reducing the level of “benefit dependency” have gained prominence. However, such policies rest on shaky empirical evidence. Systematic collections of national “caseload” data are rare, social security programmes overlap and administrative categories vary over time. The internationally inconsistent treatment of national transfer programmes provides a further challenge for cross‐national comparisons. This article first identifies and discusses several of these problems, and ways in which they may be addressed. It then employs administrative claimant data from six European countries as a way of illustrating trends over time and across countries. The underlying aim is to explore the scientific potential of benefit recipient numbers as an indicator for welfare state change over time and across countries.