bluuebunny/crossref_metadata_2025 huggingface dataset:
The tissue effect of argon‐plasma coagulation with prior submucosal injection (Hybrid‐APC) versus standard APC: A randomized ex‐vivo study
Authors: Manner Hendrik , Neugebauer Alexander , Scharpf Marcus , Braun Kirsten , May Andrea , Ell Christian , Fend Falko , Enderle Markus D
Published: July 2014

Background

Thermal ablation for Barrett's oesophagus has widely been established in gastrointestinal endoscopy during the last decade. The mainly used methods of radiofrequency ablation (RFA) and argon‐plasma coagulation (APC) carry a relevant risk of stricture formation of up to 5–15%. Newer ablation techniques that are able to overcome this disadvantage would therefore be desirable. The aim of the present study was to compare the depth of tissue injury of the new method of Hybrid‐APC versus standard APC within a randomized study in a porcine oesophagus model.

Methods

Using a total of eight explanted pig oesophagi, 48 oesophageal areas were ablated either by standard or Hybrid‐APC (APC with prior submucosal fluid injection) using power settings of 50 and 70 W. The depth of tissue injury to the oesophageal wall was analysed macroscopically and histopathologically.

Results

Using 50 W, mean coagulation depth was 937 ± 469 µm during standard APC, and 477 ± 271 µm during Hybrid‐APC (p  = 0.064). Using 70 W, coagulation depth was 1096 ± 320 µm (standard APC) and 468 ± 136 µm (Hybrid‐APC; p  = 0.003). During all settings, damage to the muscularis mucosae was observed. Using standard APC, damage to the submucosal layer was observed in 4/6 (50 W) and 6/6 cases (70 W). During Hybrid‐APC, coagulation of the submucosal layer occurred in 2/6 (50 W) and 1/6 cases (70 W). The proper muscle layer was only damaged during conventional APC (50 W: 1/6; 70 W: 3/6).

Limitations

Ex‐vivo animal study with limited number of cases.

Conclusions

Hybrid‐APC reduces coagulation depth by half in comparison with standard APC, with no thermal injury to the proper muscle layer. It may therefore lead to a lower rate of stricture formation during clinical application.
Simulation of nitrogen transport and desorption in laser welds of 21Cr–6Ni–9Mn stainless steel
Authors: Pan D. Z. , Farson D. F.
Published: July 2014

Loss of nitrogen is a concern when welding nitrogen strengthened stainless steel alloys. Building on the current understanding of the underlying mechanisms, a three-dimensional simulation of conduction mode laser weld pool development using the volume of fluid technique was developed. Weld pools formed by a moving Gaussian heat input for two different laser power densities were simulated and the transport and surface desorption of nitrogen was tracked using nitrogen macroparticles. The penetration depth and width of the weld pool predicted by the simulation was comparable to the data derived from macrographs of welds made on nitronic 40 alloy. Additionally, the 25–32% predicted decrease in nitrogen composition of the weld fusion zone by the new rate law is comparable to the literature.
Single-snapshot DOA estimation by using Compressed Sensing
Authors: Fortunati Stefano , Grasso Raffaele , Gini Fulvio , Greco Maria S , LePage Kevin
Published: July 2014

This paper deals with the problem of estimating the directions of arrival (DOA) of multiple source signals from a single observation vector of an array data. In particular, four estimation algorithms based on the theory of compressed sensing (CS), i.e., the classicalℓ1minimization (or Least Absolute Shrinkage and Selection Operator, LASSO), the fast smoothℓ0minimization, and the Sparse Iterative Covariance-Based Estimator, SPICE and the Iterative Adaptive Approach for Amplitude and Phase Estimation, IAA-APES algorithms, are analyzed, and their statistical properties are investigated and compared with the classical Fourier beamformer (FB) in different simulated scenarios. We show that unlike the classical FB, a CS-based beamformer (CSB) has some desirable properties typical of the adaptive algorithms (e.g., Capon and MUSIC) even in the single snapshot case. Particular attention is devoted to the super-resolution property. Theoretical arguments and simulation analysis provide evidence that a CS-based beamformer can achieve resolution beyond the classical Rayleigh limit. Finally, the theoretical findings are validated by processing a real sonar dataset.
Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative
Authors: Rose Shawn , Dave Jenny , Millo Corina , Naik Haley B , Siegel Evan L , Mehta Nehal N
Published: July 2014

Introduction

Psoriasis and psoriatic arthritis (PsA) increase cardiovascular disease (CVD) risk, but surrogate markers for CVD in these disorders are inadequate. Because the presence of sacroiliitis may portend more severe PsA, we hypothesized that sacroiliitis defined by computed tomography (CT) would be associated with increased vascular inflammation defined by 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which is an established measure of CVD.

Methods

Participants (n = 65) underwent whole-body FDG-PET/CT. Metabolic activity of the aorta was measured using the maximal standardized uptake value (SUVmax), a measure of atherosclerotic plaque activity. The primary outcome was aortic vascular inflammation. Linear regression (with β-coefficients (β) and P-values reported for PsA and sacroiliitis) was used to adjust for CVD risk factors to determine associations of PsA or sacroiliitis with vascular inflammation. Likelihood ratio testing was performed to evaluate the contribution of sacroiliitis to vascular disease estimation compared to the effects of PsA and traditional CVD risk factors.

Results

Vascular inflammation (measured as SUVmax) was greater (P < 0.001) in patients with sacroiliitis (mean ± SD = 7.33 ± 2.09) defined by CT compared to those without sacroiliitis (6.39 ± 1.49, P = 0.038). There were associations between PsA and aortic inflammation (β = 0.124, P < 0.001) and between sacroiliitis and aortic inflammation (β = 0.270, P < 0.001) after adjusting for CVD risk factors. Sacroiliitis predicted vascular inflammation beyond PsA and CVD risk factors (χ2 = 124.6, P < 0.001).

Conclusions

Sacroiliitis is associated with increased vascular inflammation detected by FDG-PET/CT, suggesting that sacroiliac joint disease may identify patients at greater risk for CVD. Large, ongoing prospective studies are required to confirm these findings.
Safety and feasibility of umbilical cord mesenchymal stem cells in treatment-refractory systemic lupus erythematosus nephritis: time for a double-blind placebo-controlled trial to determine efficacy
Authors: Woodworth Thasia G , Furst Daniel E
Published: July 2014

As translational clinical researchers familiar with the risk-benefit of hematopoietic stem cell transplantation in autoimmune diseases, we are intrigued by the recent report of umbilical cord mesenchymal stem cell (UC-MSC) transplantation in treatment-refractory systemic lupus erythematosus nephritis by Wang and colleagues. They report the results of an open-label single-arm multicenter phase I/II study. This stimulated us to examine whether collective data from this group provide sufficient evidence for the feasibility, safety, dose rationale, and potential efficacy of UC-MSCs to conduct a randomized controlled trial in such patients. Results, though confounded by variable baseline prednisone and immuno-suppressive treatment, appear to indicate near-term response rates of approximately 50%, which are comparable to those seen with hematopoietic stem cell transplantation but with less morbidity and mortality.
Early prediction of new-onset physical disability after intensive care unit stay: a preliminary instrument
Authors: Schandl Anna , Bottai Matteo , Holdar Ulrika , Hellgren Elisabeth , Sackey Peter
Published: July 2014

Introduction

Many intensive care unit (ICU) survivors suffer from physical disability for months after ICU stay. There is no structured method to identify patients at risk for such problems. The purpose of the study was to develop a method for early in-ICU prediction of the patient’s individual risk for new-onset physical disability two months after ICU stay.

Methods

In total, 23 potential predictors for physical disability were assessed before individual ICU discharge. Two months after ICU discharge, out of 232 eligible patients, 148 ICU survivors (64%) completed the activity of daily living (ADL) staircase questionnaire to determine new-onset physical disability.

Results

A total of 95% percent of patients had no ADL reduction prior to ICU admission. Forty-seven percent (n = 69) of questionnaire responders suffered from worsened ADL. We identified four independent predictors for new-onset physical disability: Low educational level (odds ratio (OR) = 6.8), impaired core stability (OR = 4.6), fractures (OR = 4.5) and ICU length of stay longer than two days (OR = 2.6). The predictors were included in a screening instrument. The regression coefficient of each predictor was transformed into a risk score. The sum of risk scores was related to a predicted probability for physical disability in the individual patient. The cross-validated area under receiver operating characteristics curve (AUC) for the screening instrument was 0.80.

Conclusions

Educational level is the single most important predictor for new-onset physical disability two months after ICU stay, followed by impaired core stability at ICU discharge, the presence of fractures and ICU stay longer than two days. A simple screening instrument based on these predictors can be used at ICU discharge to determine the risk for new-onset physical disability. This preliminary instrument may help clinicians to identify patients in need of support, but needs external validation prior to wider clinical use.
Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis
Authors: Atiksawedparit Pongsakorn , Rattanasiri Sasivimol , McEvoy Mark , Graham Colin A , Sittichanbuncha Yuwares , Thakkinstian Ammarin
Published: July 2014

Introduction

The aim of this study was to conduct a systematic review and meta-analysis for determining the effects of prehospital adrenaline administration on return of spontaneous circulation, hospital admission, survival to discharge and discharge with cerebral performance category 1 or 2 in out-of-hospital cardiac arrest patients.

Methods

MEDLINE and Scopus databases were searched to identify studies reported to March 2014. Study selection and data extraction were independently completed by two reviewers (PA and SR). The baseline characteristics of each study and number of events were extracted. Risk ratios (RR) and 95% confidence interval (CI) were estimated. Heterogeneity and publication bias were also explored.

Results

In total 15 studies were eligible and included in the study. Of 13 adult observational studies, four to eight studies were pooled for each outcome. These yielded a total sample size that ranged from 2,381 to 421,459. A random effects model suggested that patients receiving prehospital adrenaline were 2.89 times (95% CI: 2.36, 3.54) more likely to achieve prehospital return of spontaneous circulation than those not administered adrenaline. However, there were no significant effects on overall return of spontaneous circulation (RR = 0.93, 95% CI: 0.5, 1.74), admission (RR = 1.05, 95% CI: 0.80, 1.38) and survival to discharge (RR = 0.69, 95% CI: 0.48, 1.00).

Conclusions

Prehospital adrenaline administration may increase prehospital return of spontaneous circulation, but it does not improve overall rates of return of spontaneous circulation, hospital admission and survival to discharge.
Physical activity and telomere length in early stage breast cancer survivors
Authors: Garland Sheila N , Johnson Brad , Palmer Christina , Speck Rebecca M , Donelson Michelle , Xie Sharon X , DeMichele Angela , Mao Jun J
Published: July 2014

Introduction

Telomere length (TL) is a biomarker of accumulated cellular damage and human aging. Evidence in healthy populations suggests that TL is impacted by a host of psychosocial and lifestyle factors, including physical activity. This is the first study to evaluate the relationship between self-reported physical activity and telomere length in early stage breast cancer survivors.

Methods

A cross-sectional sample of 392 postmenopausal women with stage I-III breast cancer at an outpatient oncology clinic of a large university hospital completed questionnaires and provided a blood sample. TL was determined using terminal restriction fragment length analysis of genomic DNA isolated from peripheral blood mononuclear cells. Physical activity was dichotomized into two groups (none versus moderate to vigorous) using the International Physical Activity Questionnaire. Multivariate linear and logistic regression analyses were performed to identify factors associated with mean TL and physical activity.

Results

Among participants, 66 (17%) did not participate in any physical activity. In multivariate model adjusted for age, compared to those who participated in moderate to vigorous physical activity, women who participated in no physical activity had significantly shorter TL (adjusted coefficient β = −0.22; 95% confidence interval (CI), −0.41 to −0.03; P = .03). Non-white race, lower education and depressive symptoms were associated with lack of self-reported physical activity (P < 0.05 for all) but not TL.

Conclusion

Lack of physical activity is associated with shortened TL, warranting prospective investigation of the potential role of physical activity on cellular aging in breast cancer survivors.
Comparative population genomics reveals the domestication history of the peach, Prunus persica, and human influences on perennial fruit crops
Authors: Cao Ke , Zheng Zhijun , Wang Lirong , Liu Xin , Zhu Gengrui , Fang Weichao , Cheng Shifeng , Zeng Peng , Chen Changwen , Wang Xinwei , Xie Min , Zhong Xiao , Wang Xiaoli , Zhao Pei , Bian Chao , Zhu Yinling , Zhang Jiahui , Ma Guosheng , Chen Chengxuan , Li Yanjun , Hao Fengge , Li Yong , Huang Guodong , Li Yuxiang , Li Haiyan , Guo Jian , Xu Xun , Wang Jun
Published: July 2014

Background

Recently, many studies utilizing next generation sequencing have investigated plant evolution and domestication in annual crops. Peach, Prunus persica, is a typical perennial fruit crop that has ornamental and edible varieties. Unlike other fruit crops, cultivated peach includes a large number of phenotypes but few polymorphisms. In this study, we explore the genetic basis of domestication in peach and the influence of humans on its evolution.

Results

We perform large-scale resequencing of 10 wild and 74 cultivated peach varieties, including 9 ornamental, 23 breeding, and 42 landrace lines. We identify 4.6 million SNPs, a large number of which could explain the phenotypic variation in cultivated peach. Population analysis shows a single domestication event, the speciation of P. persica from wild peach. Ornamental and edible peach both belong to P. persica, along with another geographically separated subgroup, Prunus ferganensis.

We identify 147 and 262 genes under edible and ornamental selection, respectively. Some of these genes are associated with important biological features. We perform a population heterozygosity analysis in different plants that indicates that free recombination effects could affect domestication history. By applying artificial selection during the domestication of the peach and facilitating its asexual propagation, humans have caused a sharp decline of the heterozygote ratio of SNPs.

Conclusions

Our analyses enhance our knowledge of the domestication history of perennial fruit crops, and the dataset we generated could be useful for future research on comparative population genomics.
DawnRank: discovering personalized driver genes in cancer
Authors: Hou Jack P , Ma Jian
Published: July 2014

Large-scale cancer genomic studies have revealed that the genetic heterogeneity of the same type of cancer is greater than previously thought. A key question in cancer genomics is the identification of driver genes. Although existing methods have identified many common drivers, it remains challenging to predict personalized drivers to assess rare and even patient-specific mutations. We developed a new algorithm called DawnRank to directly prioritize altered genes on a single patient level. Applications to TCGA datasets demonstrated the effectiveness of our method. We believe DawnRank complements existing driver identification methods and will help us discover personalized causal mutations that would otherwise be obscured by tumor heterogeneity. Source code can be accessed at http://bioen-compbio.bioen.illinois.edu/DawnRank/.
Epigenetics of discordant monozygotic twins: implications for disease
Authors: Castillo-Fernandez Juan E , Spector Tim D , Bell Jordana T
Published: July 2014

Monozygotic (MZ) twins share nearly all of their genetic variants and many similar environments before and after birth. However, they can also show phenotypic discordance for a wide range of traits. Differences at the epigenetic level may account for such discordances. It is well established that epigenetic states can contribute to phenotypic variation, including disease. Epigenetic states are dynamic and potentially reversible marks involved in gene regulation, which can be influenced by genetics, environment, and stochastic events. Here, we review advances in epigenetic studies of discordant MZ twins, focusing on disease. The study of epigenetics and disease using discordant MZ twins offers the opportunity to control for many potential confounders encountered in general population studies, such as differences in genetic background, early-life environmental exposure, age, gender, and cohort effects. Recently, analysis of disease-discordant MZ twins has been successfully used to study epigenetic mechanisms in aging, cancer, autoimmune disease, psychiatric, neurological, and multiple other traits. Epigenetic aberrations have been found in a range of phenotypes, and challenges have been identified, including sampling time, tissue specificity, validation, and replication. The results have relevance for personalized medicine approaches, including the identification of prognostic, diagnostic, and therapeutic targets. The findings also help to identify epigenetic markers of environmental risk and molecular mechanisms involved in disease and disease progression, which have implications both for understanding disease and for future medical research.
Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro
Authors: Paterson Yasmin Z , Rash Nicola , Garvican Elaine R , Paillot Romain , Guest Deborah J
Published: July 2014

Introduction

Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but their mechanism of action remains poorly defined. No immune response is reported after in vivo injection of allogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the cells’ immune-privileged properties. This study further investigates these properties to determine their potential for clinical application in other tissues.

Methods

Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine peripheral blood mononuclear cells (PBMCs), and their effect on PBMC proliferation, in the presence or absence of interferon-gamma (IFN-γ) was determined. MSCs and super-antigen (sAg)-stimulated PBMCs were co-cultured directly or indirectly in transwells, and PBMC proliferation examined. Media from MSC culture were harvested and used for PBMC culture; subsequent PBMC proliferation and gene expression were evaluated and media assayed for IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-10 and IL-6 proteins with enzyme-linked immunosorbent assay (ELISA).

Results

Co-culture of PBMCs with ESCs or dESCs did not affect baseline proliferation, whereas co-culture with MSCs significantly suppressed baseline proliferation. Stimulation of PBMC proliferation by using super-antigens (sAgs) was also suppressed by co-culture with MSCs. Inhibition was greatest with direct contact, but significant inhibition was produced in transwell culture and by using MSC-conditioned media, suggesting that soluble factors play a role in MSC-mediated immune suppression. The MSCs constitutively secrete IL-6, even in the absence of co-culture with PBMCs. MSC-conditioned media also brought about a change in the cytokine-expression profile of sAg-stimulated PBMCs, significantly reducing PBMC expression of IL-6, IFN-γ, and TNF-α.

Conclusions

Equine MSCs and ESCs possess a degree of innate immune privilege, and MSCs secrete soluble factors that suppress PBMC proliferation and alter cytokine expression. These properties may make possible the future clinical use of allogeneic stem cells to help standardize and broaden the scope of treatment of tissue injuries.
Evaluation of Assumptions Used in Engineering Practice to Model Buildings Isolated with Triple Pendulum Isolators in SAP2000
Authors: Giammona Anthony P. , Ryan Keri L. , Dao Nhan D.
Published: July 2014

The commercial software platform SAP2000 has been used to design base isolated buildings supported by Triple PendulumTM isolators; however, limited full-scale test data are available to validate the use of the software for this application. Additionally, previous work has demonstrated that several pitfalls must be avoided when modeling these types of structures in SAP2000. The ability of SAP2000 to predict key engineering demand parameters used in the design of a base-isolated building is examined by using methods and assumptions employed in current design practice. The SAP2000 analysis results are compared to the data obtained from shake table tests of a full-scale base-isolated building and comparable predictions obtained from a more complex OpenSees analysis model of the same building. This study suggests that when methods and assumptions common to engineering practice are applied, SAP2000 can predict the responses with sufficient accuracy for design.
Epigenetic Regulation of Uterine Biology by Transcription Factor KLF11 via Posttranslational Histone Deacetylation of Cytochrome p450 Metabolic Enzymes
Authors: Zheng Ye , Tabbaa Zaid M. , Khan Zaraq , Schoolmeester John K. , El-Nashar Sherif , Famuyide Abimbola , Keeney Gary L. , Daftary Gaurang S.
Published: July 2014

Endocrine regulation of uterine biology is critical for embryo receptivity and human reproduction. Uterine endometrium depends on extrinsic sex steroid input and hence likely has mechanisms that enable adaptation to hormonal variation. Emerging evidence suggests that sex steroid bioavailability in the endometrium is determined by adjusting their metabolic rate and fate via regulation of cytochrome (CYP) p450 enzymes. The CYP enzymes are targeted by ubiquitously expressed Sp/Krüppel-like (Sp/KLF) transcription factors. Specifically, KLF11 is highly expressed in reproductive tissues, regulates an array of endocrine/metabolic pathways via epigenetic histone-based mechanisms and, when aberrantly expressed, is associated with diabetes and reproductive tract diseases, such as leiomyoma and endometriosis. Using KLF11 as a model to investigate epigenetic regulation of endometrial first-pass metabolism, we evaluated the expression of a comprehensive array of metabolic enzymes in Ishikawa cells. KLF11 repressed most endometrial CYP enzymes. To characterize KLF11-recruited epigenetic regulatory mechanisms, we focused on the estrogen-metabolizing enzyme CYP3A4. KLF11 expression declined in secretory phase endometrial epithelium associated with increased CYP3A4 expression. Additionally, KLF11 bound to CYP3A4 promoter GC elements and thereby repressed promoter, message, protein as well as enzymatic function. This repression was epigenetically mediated, because KLF11 colocalized with and recruited the corepressor SIN3A/histone deacetylase resulting in selective deacetylation of the CYP3A4 promoter. Repression was reversed by a mutation in KLF11 that abrogated cofactor recruitment and binding. This repression was also pharmacologically reversible with an histone deacetylase inhibitor. Pharmacological alteration of endometrial metabolism could have long-term translational implications on human reproduction and uterine disease.
P300-mediated acetylation of COMMD1 regulates its stability and the ubiquitination/nucleolar translocation of NF-κB/RelA
Authors: O'Hara Andrew , Simpson James , Morin Pierre , Loveridge Carolyn J , Williams Ann C , Novo Sonia , Stark Lesley A.
Published: July 2014

Nucleolar sequestration of RelA is an important mechanism for regulating NF-κB transcriptional activity. COMMD1(MURR1) facilitated ubiquitination acts as a critical nucleolar targeting signal for RelA, but how this ubiquitination is regulated, and how it differs from cytokine-mediated ubiquitination which causes proteasomal degradation of RelA, is poorly understood. Here we report a novel role for p300 in controlling stimulus specific ubiquitination of RelA, through modulation of COMMD1. We show that p300 is required for stress-mediated ubiquitination and nucleolar translocation of RelA, but that this effect is indirect. We also demonstrate that COMMD1 is acetylated by p300 and that acetylation protects COMMD1 from XIAP-mediated proteosomal degradation. Furthermore, we demonstrate that COMMD1 acetylation is enhanced by aspirin-mediated stress, and that this acetylation is absolutely required for the protein to bind RelA under these conditions. In contrast, TNF has no effect on COMMD1 acetylation. Finally, we demonstrate these findings have relevance in a whole tissue setting. These data offer a new paradigm for regulating NF-κB transcriptional activity, and the multiple other pathways controlled by COMMD1.
STAG2 promotes error correction in mitosis by regulating kinetochore-microtubule attachments
Authors: Kleyman Marianna , Kabeche Lilian , Compton Duane A.
Published: July 2014

Mutations in the STAG2 gene are present in approximately 20% of tumors from different tissues of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss of function mutations are usually aneuploid and display elevated frequencies of lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of chromosomal instability (CIN) arising from persistent errors in kinetochore-microtubule (kMT) attachment. To determine whether loss of STAG2 increases the rate of formation of kMT attachment errors or decreases the rate of their correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does not impair bipolar spindle formation or delay mitotic progression. Instead, loss of STAG2 permits excessive centromere stretch along with hyper-stabilization of kMT attachments. STAG2-deficient cells mislocalize Bub1 kinase, Bub3 and the chromosome passenger complex. Importantly, strategically destabilizing kMT attachments in tumor cells harboring STAG2 mutations by overexpression of the microtubule destabilizing enzymes MCAK and Kif2B decreased the rate of lagging chromosomes and reduced the rate of chromosome missegregation. These data demonstrate that STAG2 promotes the correction of kMT attachment errors to ensure faithful chromosome segregation during mitosis.
Phagosome maturation during endosome interaction revealed by partial rhodopsin processing in retinal pigment epithelium
Authors: Wavre-Shapton Silène T. , Meschede Ingrid P. , Seabra Miguel C. , Futter Clare E.
Published: July 2014

Defects in phagocytosis and degradation of photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE) are associated with aging and retinal disease.

The daily burst of rod outer segment (ROS) phagocytosis by the RPE provides a unique opportunity to analyse phagosome processing in vivo. In mouse retinae phagosomes containing stacked rhodopsin-rich discs were identified by immuno-electron microscopy. Early apical phagosomes stained with both cytoplasmic and intradiscal domain rhodopsin antibodies. During phagosome maturation a remarkably synchronised loss of the cytoplasmic epitope coincided with movement to the cell body and preceded phagosome:lysosome fusion and disc degradation. Loss of the intradiscal rhodopsin epitope and disc digestion occurred upon fusion with cathepsin D-positive lysosomes. The same sequential stages of phagosome maturation were identified in cultured RPE and macrophages challenged with isolated POS. Loss of the cytoplasmic rhodopsin epitope was insensitive to pH but sensitive to protease inhibition and co-incided with interaction of phagosomes with endosomes. Thus, during prelysosomal maturation of ROS-containing phagosomes limited rhodopsin processing occurs upon interaction with endosomes. This potentially provides a sensitive readout of phagosome:endosome interactions applicable to multiple phagocytes.
Degradation of S-RNase in compatible pollen tubes ofSolanum chacoenseinferred by immunogold labeling
Authors: Boivin Nicolas , Morse David , Cappadocia Mario
Published: July 2014

The flowering plant Solanum chacoense uses an S-RNase based self-incompatibility system in order to reject pollen that share the same genes at the S-locus (S-haplotype) with the style (an incompatible reaction). Two different models have been advanced to explain how compatible pollen tubes are protected from the cytotoxic effects of the S-RNase, sequestration of the S-RNase in a vacuolar compartment or degradation of the S-RNase in the cytoplasm. Here we examine the subcellular distribution of an S11-RNase 18 and 24 hours post pollination (hpp) in compatible and incompatible crosses by immunogold labeling and transmission electron microscopy. We find that the S-RNase is present in the cytoplasm of both compatible and incompatible crosses by 18 hpp, but that almost all the cytoplasmic S-RNase is degraded by 24 hpp in compatible crosses. These results provide compelling evidence that S-RNases are degraded in compatible but not in incompatible pollen tubes.
Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals
Authors: Seldin Marcus M. , Byerly Mardi S. , Petersen Pia S. , Swanson Roy , Balkema-Buschmann Anne , Groschup Martin H. , Wong G. William
Published: July 2014

Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related non-hibernating tree squirrels, leading to the suggestion that hibernation-specific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver–brain circuit may couple seasonal changes in the environment to alterations in physiology.
Chill coma temperatures appear similar along a latitudinal gradient, in contrast to divergent chill coma recovery times, in two widespread ant species
Authors: Maysov Andrey
Published: July 2014

Populations of widely distributed ectotherms demonstrate different cold resistance corresponding to the local climate. However, efficiently thermoregulating ectotherms could avoid divergence in cold resistance. Two species of ants, previously shown to even out latitudinal differences of mean summer temperatures in their nests, were used to test this hypothesis by comparing the temperature dependence of cold resistance in three distant populations (from 50°, 60° and 67°N). The species differ in habitat preferences, one (Myrmica rubra) being less stenotopic than the other (M. ruginodis). Therefore, three different predictions were made about their cold resistance: along the latitudinal gradient, it might be similar within the two species (because of thermoregulation within nests/habitats) or similar only in M. rubra (as a result of thermoregulation among habitats), or divergent at least in M. rubra (no effect of thermoregulation). Among populations of both species, neither differences nor latitudinal trends in chill coma temperature were statistically significant after 11 months of standard conditions, with or without cold hardening. In contrast, recovery time significantly differed among populations in both species, although its latitudinal trends were strongly curvilinear: in M. rubra, the intermediate population tended towards the slowest recovery, and in M. ruginodis, it tended towards the fastest. After 22 months, the patterns remained the same, except that M. ruginodis showed a significant linear latitudinal trend in chill coma temperature (with no significant populational differences). Hence, thermoregulation, both within and among habitats, apparently does keep chill coma temperatures similar. Recovery rate demonstrates divergence, but its curvilinear trends suggest a connection with climates experienced by ancestral populations.
Do Poverty Traps Exist? Assessing the Evidence
Authors: Kraay Aart , McKenzie David
Published: July 2014

A “poverty trap” can be understood as a set of self-reinforcing mechanisms whereby countries start poor and remain poor: poverty begets poverty, so that current poverty is itself a direct cause of poverty in the future. The idea of a poverty trap has this striking implication for policy: much poverty is needless, in the sense that a different equilibrium is possible and one-time policy efforts to break the poverty trap may have lasting effects. But what does the modern evidence suggest about the extent to which poverty traps exist in practice and the underlying mechanisms that may be involved? The main mechanisms we examine include S-shaped savings functions at the country level; “big-push” theories of development based on coordination failures; hunger-based traps which rely on physical work capacity rising nonlinearly with food intake at low levels; and occupational poverty traps whereby poor individuals who start businesses that are too small will be trapped earning subsistence returns. We conclude that these types of poverty traps are rare and largely limited to remote or otherwise disadvantaged areas. We discuss behavioral poverty traps as a recent area of research, and geographic poverty traps as the most likely form of a trap. The resulting policy prescriptions are quite different from the calls for a big push in aid or an expansion of microfinance. The more-likely poverty traps call for action in less-traditional policy areas such as promoting more migration.
The Research Productivity of New PhDs in Economics: The Surprisingly High Non-Success of the Successful
Authors: Conley John P. , Önder Ali Sina
Published: July 2014

We study the research productivity of new graduates from North American PhD programs in economics from 1986 to 2000. We find that research productivity drops off very quickly with class rank at all departments, and that the rank of the graduate departments themselves provides a surprisingly poor prediction of future research success. For example, at the top ten departments as a group, the median graduate has fewer than 0.03 American Economic Review (AER)–equivalent publications at year six after graduation, an untenurable record almost anywhere. We also find that PhD graduates of equal percentile rank from certain lower-ranked departments have stronger publication records than their counterparts at higher-ranked departments. In our data, for example, Carnegie Mellon's graduates at the 85th percentile of year-six research productivity outperform 85th percentile graduates of the University of Chicago, the University of Pennsylvania, Stanford, and Berkeley. These results suggest that even the top departments are not doing a very good job of training the great majority of their students to be successful research economists. Hiring committees may find these results helpful when trying to balance class rank and place of graduate in evaluating job candidates, and current graduate students may wish to re-evaluate their academic strategies in light of these findings.
Tεστ Eπικοινωνιακής Aνάπτυξης (ΤΕΑ) - Κλίμακες για την πρώιμη εκτίμηση της επικοινωνιακής και γλωσσικής ανάπτυξης παιδιών ηλικίας 8-30 μηνών: Πιλοτικά δεδομένα και βασικές ψυχομετρικές ιδιότητες
Authors: Karousou Alexandra , Petrogiannis Constantinos
Published: July 2014

Η πρώιμη εκτίμηση της επικοινωνιακής και γλωσσικής ανάπτυξης των παιδιών με στόχο τον έγκαιρο εντοπισμό και την πρόληψη τυχόν καθυστέρησης ή διαταραχών αποτελεί σημαντική ανάγκη της κλινικής και εκπαιδευτικής πρακτικής. Στόχος της παρούσας εργασίας είναι η πιλοτική διερεύνηση βασικών ψυχομετρικών ιδιοτήτων του Τεστ Επικοινωνιακής Ανάπτυξης (ΤΕΑ), ενός νέου ερωτηματολογίου γονέων για την πρώιμη εκτίμηση του επικοινωνιακού/γλωσσικού επιπέδου παιδιών ηλικίας 8 έως 30 μηνών, το οποίο αναπτύχθηκε και βρίσκεται υπό στάθμιση στη χώρα μας. Παρουσιάζονται οι κλίμακες και υποκλίμακες του ΤΕΑ, καθώς και η μεθοδολογία που ακολουθήθηκε για την ανάπτυξή τους και τη διερεύνηση της εγκυρότητάς τους. Επίσης, παρατίθενται στοιχεία για τους τομείς επικοινωνιακής/γλωσσικής ανάπτυξης που καλύπτει το ΤΕΑ: προλεκτική επικοινωνία, κατανόηση της γλώσσας, εκφραστικό λεξιλόγιο, μορφολογία και σύνταξη. Mε βάση πιλοτικά δεδομένα που αφορούσαν ένα δείγμα 354 παιδιών, διερευνάται η ευαισθησία των ερωτήσεων (αναπτυξιακών δεικτών) που περιλαμβάνει το ΤΕΑ, η αξιοπιστία εσωτερικής συνοχής, καθώς και η συγκλίνουσα και αποκλίνουσα εγκυρότητα για καθεμία από τις κλίμακες και υποκλίμακές του. Τα πρώτα ευρήματα στο σύνολό τους προσφέρουν σημαντικές ενδείξεις για την λειτουργικότητα του νέου αυτού ψυχομετρικού εργαλείου ως μέσου για την πρώιμη εκτίμηση του επικοινωνιακού/γλωσσικού επιπέδου μικρών παιδιών.
«Σιωπή! Προσεγγίζοντας την περίπτωση των μαθητών που αντιμετωπίζονται στο σχολείο ως ομοφυλόφιλοι»
Authors: Darais Konstantinos
Published: July 2014

Η σύνταξη αυτού του άρθρου βασίστηκε στη μελέτη της περίπτωσης των μαθητών που είναι ή αντιμετωπίζονται ως ομοφυλόφιλοι στο σχολικό πλαίσιο. Το ενδιαφέρον για το συγκεκριμένο θέμα, προκλήθηκε από την εμπειρική διαπίστωση του συγγραφέα, ως Σχολικού Συμβούλου, ότι στα σχολεία υπάρχουν μαθητές που δέχονται έντονη ψυχολογική, λεκτική ή σωματική βία, επειδή συμπεριφέρονται με τρόπους που δεν θεωρούνται «συμβατοί» με το βιολογικό και κοινωνικό τους φύλο. Οι περιπτώσεις αυτών των μαθητών προκαλούν έντονο προβληματισμό και αμηχανία στους εκπαιδευτικούς των σχολείων. Το άρθρο, αξιοποιώντας τη συγκεκριμένη βιβλιογραφία, παρουσιάζει το ψυχολογικό προφίλ αυτών των μαθητών, τους τρόπους αντιμετώπισής τους από τους συμμαθητές τους, τους εκπαιδευτικούς και τις οικογένειές τους, καθώς και τις ψυχοκοινωνικές και εκπαιδευτικές επιπτώσεις στη ζωή τους. Τέλος καταλήγει στο συμπέρασμα ότι χρειάζεται να ληφθούν μέτρα στήριξης αυτών μαθητών στο σχολικό πλαίσιο για να προστατευθεί η σωματική και ψυχική τους υγεία.
dendsort: modular leaf ordering methods for dendrogram representations in R
Authors: Sakai Ryo , Winand Raf , Verbeiren Toni , Moere Andrew Vande , Aerts Jan
Published: July 2014

Dendrograms are graphical representations of binary tree structures resulting from agglomerative hierarchical clustering. In Life Science, a cluster heat map is a widely accepted visualization technique that utilizes the leaf order of a dendrogram to reorder the rows and columns of the data table. The derived linear order is more meaningful than a random order, because it groups similar items together. However, two consecutive items can be quite dissimilar despite proximity in the order. In addition, there are 2n-1 possible orderings given n input elements as the orientation of clusters at each merge can be flipped without affecting the hierarchical structure. We present two modular leaf ordering methods to encode both the monotonic order in which clusters are merged and the nested cluster relationships more faithfully in the resulting dendrogram structure. We compare dendrogram and cluster heat map visualizations created using our heuristics to the default heuristic in R and seriation-based leaf ordering methods. We find that our methods lead to a dendrogram structure with global patterns that are easier to interpret, more legible given a limited display space, and more insightful for some cases. The implementation of methods is available as an R package, named ”dendsort”, from the CRAN package repository. Further examples, documentations, and the source code are available at [https://bitbucket.org/biovizleuven/dendsort/].
Diagnosis and management of atrial fibrillation: The latest NICE guidance
Authors: Linden Belinda
Published: July 2014

Belinda Linden gives an overview of the latest National Institute for Health and Care Excellence guidance on managing atrial fibrillation, published in June 2014
Stroke prevention in atrial fibrillation: An update
Authors: Haws Joanne
Published: July 2014

Atrial fibrillation (AF) is the most common cardiac arrhythmia and, if left untreated, is a significant risk factor for stroke and heart failure. In order to reduce AF-related stroke, it is essential that the relevant population be identified, risk stratified and offered appropriate interventions to reduce their risk. The risk of stroke is not influenced by the pattern of AF shown in the patient; paroxysmal, persistent or permanent AF. All result in an increased stroke risk and all patients should have their individual level of risk assessed accordingly. Patients at high risk of stroke should be anticoagulated without delay. There are currently suboptimal levels of anticoagulation throughout the UK which, if addressed, could potentially save a significant number of lives and reduce strokes within the population. The introduction of novel oral anticoagulants that can be offered as an alternative to warfarin should help clinicians to find acceptable treatment options for patients who are at risk.
Our family's rollercoaster journey
Authors: Lee Alison
Published: July 2014

Alison Lee shares her story of discovering that her newborn sons, Daniel and Nathan, both had heart conditions and would have to undergo open heart surgery at less than 1 month old
Modelling crown snow loads in Finland: a comparison of two methods
Authors: Lehtonen Ilari , Hoppula Petri , Pirinen Pentti , Gregow Hilppa
Published: July 2014

The spatial occurrence of heavy crown snow loads in Finland between 1961 and 2010 is studied by using for the first time a model that classifies the snow load into four different types: rime, dry snow, wet snow and frozen snow. In producing this climatology, we used meteorological observations made at 29 locations across Finland. The model performance is evaluated against classified daily images of canopy snow cover and with the help of two short case studies. The results are further compared to those achieved with a simpler method used in previous studies. The heaviest crown snow loads are found to occur typically in eastern Finland. The new method reveals that this holds not only for the total snow loads but also for the different snow load types, although there are certain differences in their geographical occurrence. The greatest benefit achieved with the new method is the inclusion of rime accretion. The forests most prone to heavy riming are those located on tree-covered hills in northern Finland, but as the terrain elevation affects riming efficiency greatly, these small-scale variations in the snow load amounts could not be described in this study in great detail. Moreover, the results are more inaccurate in northern Finland where variations in the terrain elevation are greater than elsewhere. Otherwise, the largest uncertainties in this study are related to wind speed measurements and possibly partly because of that, we were not able to detect any significant trends in the crown snow-load amounts over the study period.
Method for the quantitative measurement of collecting lymphatic vessel contraction in mice
Authors: Liao Shan , Jones Dennis , Cheng Gang , P. Padera Timothy
Published: July 2014

Collecting lymphatic vessels are critical for the transport of lymph and its cellular contents to lymph nodes for both immune surveillance and the maintenance of tissue-fluid balance. Collecting lymphatic vessels drive lymph flow by autonomous contraction of smooth muscle cells that cover these vessels. Here we describe methods using intravital microscopy to image and quantify collecting lymphatic vessel contraction in mice. Our methods allow for the measurement of the strength of lymphatic contraction of an individual lymphangion in a mouse, which has not yet been demonstrated using other published methods. The ability to study murine collecting lymphatic vessel contraction—using the methods described here or other recently published techniques—allows the field to dissect the molecular mechanisms controlling lymphatic pumping under normal and pathological conditions using the wide variety of molecular tools and genetic models available in the mouse. We have used our methods to study lymphatic contraction in physiological and inflammatory conditions. The methods described here will facilitate the further study of lymphatic function in other pathological conditions that feature lymphatic complications.
A clinically novel AIP mutation in a patient with a very large, apparently sporadic somatotrope adenoma
Authors: Salvatori Roberto , Daly Adrian F , Quinones-Hinojosa Alfredo , Thiry Albert , Beckers Albert
Published: July 2014

Heterozygous germline inactivating mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene lead to pituitary adenomas that most frequently present in the setting of familial isolated pituitary adenoma syndrome, usually as somatotropinomas and prolactinomas. More recently, they have been found in a significant percentage of young patients presenting with pituitary macroadenoma without any apparent family history. We describe the case of a 19-year-old man who presented with a gigantic somatotropinoma. His family history was negative. His peripheral DNA showed a heterozygous AIP mutation (p.I13N), while tumor tissue only had the mutated allele, showing loss of heterozygosity (LOH) and suggesting that the mutation caused the disease.

Learning points

AIP mutations may be observed in sporadic somatotrope adenomas occurring in young patients.

LOH is a strong indicator that an AIP variant is disease causing.

Somatotrope adenomas in carriers of AIP mutations are generally larger and more difficult to cure.
Improvement on Mechanical Properties of a Particle Board Made of Recycled Material Based on Tetra Brik®
Authors: Carrillo J.G. , Ventura D.A. Pool , Gamboa R.A. , Cruz-Estrada R.H.
Published: July 2014

The topic of Urban Solid Waste (USW) has become increasingly controversial in our times due to the high volumes being produced and not disposed properly; one effective way to reduce the generation of USW is finding new ways to recycling. This study proposes a means of recycling Tetra Brik® (TBr) cartons and high density polyethylene recycled containers (HDPEr), by generating an agglomerate with optimal mechanical properties in comparison with other TBr-based agglomerates. For the analysis of this material’s mechanical properties, two types of evaluation tests are carried out; flexure and screw pull-out test. Results show significant mechanical advantages over other TBr-based laminates by the integration of an HDPEr matrix to the system, thereby improving mechanical properties.