bluuebunny/crossref_metadata_2025 huggingface dataset:
Landau quantization and spin-momentum locking in topological Kondo insulators
Authors: Schlottmann P.
Published: February 2016

SmB6 has been predicted to be a strong topological Kondo insulator and experimentally it has been confirmed that at low temperatures the electrical conductivity only takes place at the surfaces of the crystal. Quantum oscillations and ARPES measurements revealed several Dirac cones on the (001) and (101) surfaces of the crystal. We considered three types of surface Dirac cones with an additional parabolic dispersion and studied their Landau quantization and the expectation value of the spin of the electrons. The Landau quantization is quite similar in all three cases and would give rise to very similar de Haas-van Alphen oscillations. The spin-momentum locking, on the other hand, differs dramatically. Without the additional parabolic dispersion the spins are locked in the plane of the surface. The parabolic dispersion, however, produces a gradual canting of the spins out of the surface plane.
Detection of DC currents and resistance measurements in longitudinal spin Seebeck effect experiments on Pt/YIG and Pt/NFO
Authors: Meier Daniel , Kuschel Timo , Meyer Sibylle , Goennenwein Sebastian T. B. , Shen Liming , Gupta Arunava , Schmalhorst Jan-Michael , Reiss Günter
Published: February 2016

In this work we investigated thin films of the ferrimagnetic insulators Y 3Fe5O12 and NiFe2O4 capped with thin Pt layers in terms of the longitudinal spin Seebeck effect (LSSE). The electric response detected in the Pt layer under an out-of-plane temperature gradient can be interpreted as a pure spin current converted into a charge current via the inverse spin Hall effect. Typically, the transverse voltage is the quantity investigated in LSSE measurements (in the range of μV). Here, we present the directly detected DC current (in the range of nA) as an alternative quantity. Furthermore, we investigate the resistance of the Pt layer in the LSSE configuration. We found an influence of the test current on the resistance. The typical shape of the LSSE curve varies for increasing test currents.
On the Translation of Names in Margaret Mitchell’s Gone with the Wind: A Study in Onomastic Acculturation
Authors: Chen Lindsey N. H.
Published: February 2016

This study examines the Chinese translation of personal names in Margaret Mitchell’s Gone with the Wind (GWTW). In particular, four name forms are identified in the popular translation by Fu Dong Hua: two-character given names, Sinicized surnames, surname-less references, and fully transliterated personal names. Contrary to the conventional practice of fully transliterating foreign names, translated personal names in GWTW are unique in that they conform to Chinese naming practice, including the adoption of the common FN-GN (family name-given name) pattern and conscious selection of gender-appropriate characters. Examples of onomastically encoded power differential are also noted and discussed.
PON-Sol: prediction of effects of amino acid substitutions on protein solubility
Authors: Yang Yang , Niroula Abhishek , Shen Bairong , Vihinen Mauno
Published: February 2016

Motivation: Solubility is one of the fundamental protein properties. It is of great interest because of its relevance to protein expression. Reduced solubility and protein aggregation are also associated with many diseases.

Results: We collected from literature the largest experimentally verified solubility affecting amino acid substitution (AAS) dataset and used it to train a predictor called PON-Sol. The predictor can distinguish both solubility decreasing and increasing variants from those not affecting solubility. PON-Sol has normalized correct prediction ratio of 0.491 on cross-validation and 0.432 for independent test set. The performance of the method was compared both to solubility and aggregation predictors and found to be superior. PON-Sol can be used for the prediction of effects of disease-related substitutions, effects on heterologous recombinant protein expression and enhanced crystallizability. One application is to investigate effects of all possible AASs in a protein to aid protein engineering.

Availability and implementation: PON-Sol is freely available at http://structure.bmc.lu.se/PON-Sol. The training and test data are available at http://structure.bmc.lu.se/VariBench/ponsol.php

Contact:  mauno.vihinen@med.lu.se

Supplementary information:  Supplementary data are available at Bioinformatics online.
FRAGSION: ultra-fast protein fragment library generation by IOHMM sampling
Authors: Bhattacharya Debswapna , Adhikari Badri , Li Jilong , Cheng Jianlin
Published: February 2016

Motivation: Speed, accuracy and robustness of building protein fragment library have important implications in de novo protein structure prediction since fragment-based methods are one of the most successful approaches in template-free modeling (FM). Majority of the existing fragment detection methods rely on database-driven search strategies to identify candidate fragments, which are inherently time-consuming and often hinder the possibility to locate longer fragments due to the limited sizes of databases. Also, it is difficult to alleviate the effect of noisy sequence-based predicted features such as secondary structures on the quality of fragment.

Results: Here, we present FRAGSION, a database-free method to efficiently generate protein fragment library by sampling from an Input–Output Hidden Markov Model. FRAGSION offers some unique features compared to existing approaches in that it (i) is lightning-fast, consuming only few seconds of CPU time to generate fragment library for a protein of typical length (300 residues); (ii) can generate dynamic-size fragments of any length (even for the whole protein sequence) and (iii) offers ways to handle noise in predicted secondary structure during fragment sampling. On a FM dataset from the most recent Critical Assessment of Structure Prediction, we demonstrate that FGRAGSION provides advantages over the state-of-the-art fragment picking protocol of ROSETTA suite by speeding up computation by several orders of magnitude while achieving comparable performance in fragment quality.

Availability and implementation: Source code and executable versions of FRAGSION for Linux and MacOS is freely available to non-commercial users at http://sysbio.rnet.missouri.edu/FRAGSION/. It is bundled with a manual and example data.

Contact:  chengji@missouri.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
RIPPER: a framework for MS1 only metabolomics and proteomics label-free relative quantification
Authors: Van Riper Susan K. , Higgins LeeAnn , Carlis John V. , Griffin Timothy J.
Published: February 2016

Summary: RIPPER is a framework for mass-spectrometry-based label-free relative quantification for proteomics and metabolomics studies. RIPPER combines a series of previously described algorithms for pre-processing, analyte quantification, retention time alignment, and analyte grouping across runs. It is also the first software framework to implement proximity-based intensity normalization. RIPPER produces lists of analyte signals with their unnormalized and normalized intensities that can serve as input to statistical and directed mass spectrometry (MS) methods for detecting quantitative differences between biological samples using MS.

Availability and implementation:  http://www.z.umn.edu/ripper.

Contact:  vanr0014@umn.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Mammary-tumor-educated B cells acquire LAP/TGF-β and PD-L1 expression and suppress anti-tumor immune responses
Authors: Zhang Yu , Morgan Richard , Chen Chuan , Cai Yancheng , Clark Emily , Khan Wasif Noor , Shin Seung-Uon , Cho Hyun-Mi , Al Bayati Ahmed , Pimentel Augustin , Rosenblatt Joseph D.
Published: February 2016

B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild-type (WT) mice but show reduced growth in B-cell-deficient μ−/− BALB/c mice (BCDM). WT mice demonstrate extensive B-cell infiltration into the tumor bed, reduced CD8+ T cell and CD49+ NK cell infiltration, and markedly reduced cytolytic T-cell response relative to BCDM. Expression of LAP/TGF-β1, CD80, CD86 and PD-L1 is significantly increased in tumor-infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-β1 expression on TIL-B progressively increased from 5.4±1.7% on day 8 to 43.1±6.1% by day 21 post tumor implantation. Co-culture of EMT-6 tumor cells with Naive-B cells ex vivo generated B cells (EMT6-B) with a similar immunophenotype to TIL-B. Purified TIL-B, or in-vitro-generated EMT6-B suppressed CD4+, CD8+ and CD4+CD25− T-cell proliferation, and Th1 cytokine secretion, and also suppressed purified NK-cell proliferation in response to IL-15, compared to naive splenic B cells. Acquired B regulatory function required direct tumor cell: B-cell contact, and was partially reversed by antibody to TGF-β or PD-L1, leading to tumor rejection in vivo. B-cell acquisition of a suppressive phenotype following tumor infiltration may result in profound inhibition of T-cell anti-tumor responses.
Radio-loud Narrow Line Seyfert 1 under a different perspective: a revised black hole mass estimate from optical spectropolarimetry
Authors: Baldi Ranieri D. , Capetti Alessandro , Robinson Andrew , Laor Ari , Behar Ehud
Published: February 2016

Several studies indicate that radio-loud (RL) active galactic nuclei (AGNs) are produced only by the most massive black holes (BH), MBH ∼ 108–1010 M⊙. This idea has been challenged by the discovery of RL Narrow Line Seyfert 1 (RL NLSy1), having estimated masses of MBH ∼ 106–107 M⊙. However, these low MBH estimates might be due to projection effects. Spectropolarimetry allows us to test this possibility by looking at RL NLSy1s under a different perspective, i.e. from the viewing angle of the scattering material. We here report the results of a pilot study of Very Large Telescope spectropolarimetric observations of the RL NLSy1 PKS 2004−447. Its polarization properties are remarkably well reproduced by models in which the scattering occurs in an equatorial structure surrounding its broad-line region, seen close to face-on. In particular, we detect a polarized Hα line with a width of ∼9000 km s−1, ∼6 times broader than the width seen in direct light. This corresponds to a revised estimate of MBH ∼ 6 × 108 M⊙, well within the typical range of RL AGN. The double-peaked polarized broad Hα profile of the target suggests that the rare combination of the orientation effects and a broad line region dominated by the rotation might account for this class of objects, casting doubts on the virial estimates of BH mass for type-I AGN.
Probing O-enrichment in C-rich dust planetary nebulae
Authors: García-Hernández D. A. , Ventura P. , Delgado-Inglada G. , Dell'Agli F. , Di Criscienzo M. , Yagüe A.
Published: February 2016

The abundance of O in planetary nebulae (PNe) has been historically used as a metallicity indicator of the interstellar medium (ISM), where they originated; e.g. it has been widely used to study metallicity gradients in our Galaxy and beyond. However, clear observational evidence for O self-enrichment in low-metallicity Galactic PNe with C-rich dust has been recently reported. Here, we report asymptotic giant branch (AGB) nucleosynthesis predictions for the abundances of the CNO elements and helium in the metallicity range Z⊙/4 < Z < 2 Z⊙. Our AGB models, with diffusive overshooting from all the convective borders, predict that O is overproduced in low-Z low-mass (∼1–3 M⊙) AGB stars and nicely reproduce the recent O overabundances observed in C-rich dust PNe. This confirms that O is not always a good proxy of the original ISM metallicity and other chemical elements such as Cl or Ar should be used instead. The production of oxygen by low-mass stars should be thus considered in galactic-evolution models.
Baseline Sensitivity of Botrytis cinerea to the Succinate Dehydrogenase Inhibitor Isopyrazam and Efficacy of this Fungicide
Authors: Song Yingying , Zhang Zhengqun , Chen Lele , He Leiming , Lu Hongbao , Ren Yupeng , Mu Wei , Liu Feng
Published: February 2016

Isopyrazam is a new broad-spectrum, foliar-absorbed and -translocated succinate dehydrogenase inhibitor fungicide. In this study, 159 Botrytis cinerea isolates collected from different geographical regions of Shandong Province of China were characterized for baseline sensitivity to isopyrazam. Furthermore, the protective and curative activity of isopyrazam on strawberry fruit and the control efficacy in the field were also determined. In contrast to its mycelial growth, the spore germination of B. cinerea was inhibited completely by lower concentrations of isopyrazam, about 1 μg ml−1 on yeast-peptone-acetate medium. Frequency distributions of isopyrazam 50% effective concentration (EC50) values were unimodal curves, with mean EC50 values of 0.07 ± 0.04 (standard deviation) and 0.68 ± 0.36 μg ml−1 for the inhibition of spore germination and mycelial growth, respectively. In addition, there was no positive multiple resistance between isopyrazam and other classes of botryticides such as diethofencarb, iprodione, pyrimethanil, or SYP-Z048. In field trials conducted during 2014 and 2015, isopyrazam used at a concentration of active ingredient at 150 and 200 g ha−1 provided a control efficacy ranging from 76.7 to 87.8% on leaves and from 81.5 to 90.7% on fruit. These results suggest that isopyrazam has the potential to play an important role in the management of gray mold.
Regression Analysis of Optical Coherence Tomography Disc Variables for Glaucoma Diagnosis
Authors: Richter Grace M. , Zhang Xinbo , Tan Ou , Francis Brian A. , Chopra Vikas , Greenfield David S. , Varma Rohit , Schuman Joel S. , Huang David
Published: February 2016

Purpose:

To report diagnostic accuracy of optical coherence tomography (OCT) disc variables using both time-domain (TD) and Fourier-domain (FD) OCT, and to improve the use of OCT disc variable measurements for glaucoma diagnosis through regression analyses that adjust for optic disc size and axial length–based magnification error.

Design:

Observational, cross-sectional.

Participants:

In total, 180 normal eyes of 112 participants and 180 eyes of 138 participants with perimetric glaucoma from the Advanced Imaging for Glaucoma Study.

Methods:

Diagnostic variables evaluated from TD-OCT and FD-OCT were: disc area, rim area, rim volume, optic nerve head volume, vertical cup-to-disc ratio (CDR), and horizontal CDR. These were compared with overall retinal nerve fiber layer thickness and ganglion cell complex. Regression analyses were performed that corrected for optic disc size and axial length. Area-under-receiver-operating curves (AUROC) were used to assess diagnostic accuracy before and after the adjustments. An index based on multiple logistic regression that combined optic disc variables with axial length was also explored with the aim of improving diagnostic accuracy of disc variables.

Main Outcome Measure:

Comparison of diagnostic accuracy of disc variables, as measured by AUROC.

Results:

The unadjusted disc variables with the highest diagnostic accuracies were: rim volume for TD-OCT (AUROC=0.864) and vertical CDR (AUROC=0.874) for FD-OCT. Magnification correction significantly worsened diagnostic accuracy for rim variables, and while optic disc size adjustments partially restored diagnostic accuracy, the adjusted AUROCs were still lower. Axial length adjustments to disc variables in the form of multiple logistic regression indices led to a slight but insignificant improvement in diagnostic accuracy.

Conclusions:

Our various regression approaches were not able to significantly improve disc-based OCT glaucoma diagnosis. However, disc rim area and vertical CDR had very high diagnostic accuracy, and these disc variables can serve to complement additional OCT measurements for diagnosis of glaucoma.
Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer
Authors: Md Din Norshamsiah , Tomkins-Netzer Oren , Talat Lazha , Taylor Simon R.J. , Isa Hazlita , Bar Asaf , Lightman Sue
Published: February 2016

Purpose:

To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis–related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness.

Patients and Methods:

Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP.

Results:

IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043).

Conclusions:

Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.
Evaluation of Nonmydriatic Hand-held Optic Disc Photography Grading in the Philadelphia Glaucoma Detection and Treatment Project
Authors: Waisbourd Michael , Bond Emily A. , Sullivan Timothy , Hu Wanda D. , Shah Sonya B. , Molineaux Jeanne , Sembhi Harjeet , Spaeth George L. , Myers Jonathan S. , Hark Lisa A. , Katz L. Jay
Published: February 2016

Purpose:

To determine the reproducibility of optic disc photograph grading obtained by a hand-held fundus camera and to determine the diagnostic value of these photographs in detecting patients with glaucoma in a community-based glaucoma-detection program.

Materials and Methods:

Patients underwent slit-lamp examination by an ophthalmologist who graded each patient’s optic discs using 2 methods: cup-to-disc ratio (CDR) and disc damage likelihood scale (DDLS). After a comprehensive glaucoma evaluation, patients were diagnosed as having “glaucoma,” “glaucoma suspect,” or “no glaucoma.” Nonmydriatic, monoscopic optic disc photographs were then taken with a portable digital imaging device. On a different day, the same examiner and a second observer graded the disc photographs in a masked manner and determined a diagnostic impression based only on the disc photographs.

Results:

Of the 1649 patients examined, 119 subjects were randomly selected according to 3 groups of diagnoses: “glaucoma” (n=36), “glaucoma suspect” (n=50), and “no glaucoma” (n=33). For CDR, the intraobserver agreement was 0.71 and the interobserver agreement was 0.69. For disc DDLS, the intraobserver agreement was 0.65 and the interobserver agreement was 0.67. The area under the receiver-operating characteristic distinguishing between normal and glaucoma was 0.88 and 0.86 for CDR and disc DDLS, respectively.

Conclusions:

Nonmydriatic, monoscopic disc photographs obtained by a hand-held camera had only moderate disc grading reproducibility. This could be due to a reduced quality of images, making interpretation more challenging, due to taking photographs through small pupils by a hand-held camera and the high percentage of patients with significant cataracts.
Outcomes of Trabeculectomy With Mitomycin-C in Uveitis Associated With Vogt-Koyanagi-Harada Disease
Authors: Almobarak Faisal A. , Alharbi Ali H. , Morales Jose , Aljadaan Ibrahim
Published: February 2016

Objectives:

To evaluate the outcomes of trabeculectomy with mitomycin-C (MMC) in uveitis associated with Vogt-Koyanagi-Harada disease (VKH).

Methods:

Retrospective cohort study included 27 eyes of 15 patients with uveitic glaucoma associated with VKH disease who underwent trabeculectomy with MMC as a first glaucoma procedure at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between 1992 and 2011. The main outcome measures were: the intraocular pressure (IOP), the number of antiglaucoma medications, the presence of visually threatening complications, and the need for further surgeries to control the IOP.

Results:

The mean follow-up was 78.19 months. The IOP decreased significantly from a mean of 40.15±7.0 to 13.12±6.9 mm Hg on the last follow-up (P<0.01) as well as during the whole follow-up period. The number of medications needed to control the IOP also decreased significantly from 3.89±0.6 to 1.04±1.3. The cumulative probabilities of success were 77.8%, 74.1%, 63.0%, and 51.9% at 12, 24, 36, and 48 months postoperatively, respectively. The most common complications were cataract development and progression (53.8%), hypotony (IOP≤5 mm Hg) (33.3%), choroidal effusion (7.4%), and decompressive retinopathy (7.4%). Eight eyes (29.6%) needed a second procedure to control the IOP.

Conclusions:

Trabeculectomy with MMC offers an acceptable intermediate term success and IOP control in uveitic glaucoma associated with VKH. However, significant number of eyes needed further procedures to control the pressure. Therefore, continuous monitoring of the pressure is important.
A Systematic Review of End-of-Life Visual Impairment in Open-Angle Glaucoma: An Epidemiological Autopsy
Authors: Mokhles Palwasha , Schouten Jan S. A. G. , Beckers Henny J. M. , Azuara-Blanco Augusto , Tuulonen Anja , Webers Carroll A. B.
Published: February 2016

Purpose:

Glaucoma patients are still at risk of becoming blind. It is of clinical significance to determine the risk of blindness and its causes to prevent its occurrence. This systematic review estimates the number of treated glaucoma patients with end-of-life visual impairment (VI) and blindness and the factors that are associated with this.

Methods:

A systematic literature search in relevant databases was conducted in August 2014 on end-of-life VI. A total of 2574 articles were identified, of which 5 on end-of-life VI. Several data items were extracted from the reports and presented in tables.

Results:

All studies had a retrospective design. A considerable number of glaucoma patients were found to be blind at the end of their life; with up to 24% unilateral and 10% bilateral blindness. The following factors were associated with blindness: (1) baseline severity of visual field loss: advanced stage of glaucoma or substantial visual field loss at the initial visit; (2) factors influencing progression: fluctuation of intraocular pressure (IOP) during treatment, presence of pseudoexfoliation, poor patient compliance, higher IOP; (3) longer time period: longer duration of disease and older age at death because of a longer life expectancy; and (4) coexistence of other ocular pathology.

Conclusions:

Further prevention of blindness in glaucoma patients is needed. To reach this goal, it is important to address the risk factors for blindness identified in this review, especially those that can be modified, such as advanced disease at diagnosis, high and fluctuating IOP, and poor compliance.
Ovarian Low-grade Serous Carcinoma
Authors: Okoye Ekene , Euscher Elizabeth D. , Malpica Anais
Published: February 2016

Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients’ charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow-up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no evidence of disease. Ovarian LGSC is rare with a predilection for younger patients relative to HGSC. Most LGSC cases are associated with SBT with an MP/CP, and their invasive component usually contains a micropapillary pattern. Most patients with ovarian LGSC present with advanced-stage disease and have a short-term survival advantage over patients with HGSC (estimated 5 y survival: 62.3% vs. 43.9%). However, over a prolonged period of time, this survival advantage decreases (estimated 10 y survival: 21.2% vs. 22.7%).
Significance of Paneth Cells in Histologically Unremarkable Rectal Mucosa
Authors: Pezhouh Maryam K. , Cheng Edaire , Weinberg Arthur G. , Park Jason Y.
Published: February 2016

Paneth cell metaplasia of the rectal epithelium is a common histologic finding in patients with chronic inflammatory bowel disease. However, the clinical significance of isolated Paneth cells in otherwise unremarkable rectal mucosa has not been extensively examined. This study examined the frequency and clinical correlates of rectal Paneth cells in 245 biopsies obtained from patients between the ages of 2 weeks to 20 years in a pediatric tertiary care facility from 2010 to 2011. The specimens comprised 193 endoscopic pinch biopsies and 52 rectal suction biopsies. All 245 cases were endoscopically and histologically unremarkable with no prominence of eosinophils, no altered mucosal architecture, and no inflammation. Paneth cells were present in 42 cases (17.1%), which is higher than previous reports. Only 1 of 42 patients with rectal Paneth cells was subsequently diagnosed with Crohn disease. In our study population, the finding of Paneth cells was associated with young age, and the incidence of Paneth cell cases decreased with increasing age (χ2=13.69, P=0.0002). Constipation was the most common presenting symptom in patients with rectal Paneth cells and was highly associated with the presence of Paneth cells (odds ratio 4.5, 95% confidence interval: 2.2-9.0). Paneth cells in otherwise unremarkable pediatric rectal biopsies are not rare and frequently occur in common conditions such as idiopathic constipation.
Rigidity of silicone substrates controls cell spreading and stem cell differentiation
Authors: Vertelov Grigory , Gutierrez Edgar , Lee Sin-Ae , Ronan Edward , Groisman Alex , Tkachenko Eugene
Published: February 2016

Multiple functions of cells cultured on flat substrates have been shown to depend on the elastic modulus of the substrate, E, with the dependence being strongest in a physiological range of soft tissues, corresponding to E from 0.1 to 100 kPa. Among those functions are stem cell differentiation, cell spreading, and cell signaling [1]. In the context of differentiation of mesenchymal stem cells (MSCs), substrates with E in the ranges of <4 kPa, 8-17 kPa, and >25 kPa, have been classified as soft (adipogenic) [2,3], medium rigidity (myogenic)1, and hard (osteogenic) [1], respectively. In most studies, the soft substrates are hydrogels, and variations in their elastic moduli are usually accompanied by variations in the dry mass and porosity. The paradigm of the effect of substrate rigidity on the cellular functions has been challenged by Trappmann et al. [4], who claimed that cell spreading and differentiation on hydrogel substrates depend not on the elastic moduli of the substrates, but rather on their porosity, which affects the density of adhesion points between the substrate surface and the extracellular matrix (ECM) coating on it. This claim has been rebutted by Wen at al. [3], who have used hydrogel substrates with different porosities but identical elastic moduli to show that it is the elastic modulus rather than the porosity that is key to the effect of the substrate on cell spreading and differentiation. Both publications agree, however, that there is no appreciable effect of the substrate rigidity on either cell spreading or differentiation, if the substrate is made of a silicone gel rather than a hydrogel. This conclusion appears to contradict the findings of several other groups, who reported that when cells are plated on an array of flexible silicone microposts, their spreading and differentiation depend on the rigidity of the substrate [5], and that when cell are plated on silicone gels, their differentiation depends on the gel rigidity [6]. To resolve this contradiction, we used soft, medium, and hard silicone gel substrates with elastic moduli of 0.5, 16, and 64 kPa, respectively, (Fig.1) to perform experiments similar to those reported in Refs.4 and 3, testing the dependence of differentiation and spreading of MSCs and of spreading of fibroblasts and keratinocytes on the substrate rigidity.
Single-chromosome aneuploidy commonly functions as a tumor suppressor
Authors: Sheltzer Jason M. , Ko Julie H. , Habibe Burgos Nicole C. , Chung Erica S. , Meehl Colleen M. , Passerini Verena , Storchova Zuzana , Amon Angelika
Published: February 2016

Whole-chromosome aneuploidy is a hallmark of human malignancies. The prevalence of chromosome segregation errors in cancer – first noted more than 100 years ago – has led to the widespread belief that aneuploidy plays a crucial role in tumor development. Here, we set out to test this hypothesis. We transduced congenic euploid and trisomic fibroblasts with 14 different oncogenes or oncogene combinations, thereby creating genetically-matched cancer cell lines that differ only in karyotype. Surprisingly, nearly all aneuploid cell lines divided slowlyin vitro, formed few colonies in soft agar, and grew poorly as xenografts, relative to matched euploid lines. Similar results were obtained when comparing a near-diploid human colorectal cancer cell line with derivatives of that line that harbored extra chromosomes. Only a few aneuploid lines grew at close to wild-type levels, and no aneuploid line exhibited greater tumorigenic capabilities than its euploid counterpart. These results demonstrate that rather than promoting tumorigenesis, aneuploidy, particularly single chromosome gains, can very often function as a tumor suppressor. Moreover, our results suggest one potential way that cancers can overcome the tumor suppressive effects of aneuploidy: rapidly-growing aneuploid cell lines that had evolvedin vitroorin vivodemonstrated recurrent karyotype changes that were absent from their euploid counterparts. Thus, the genome-destabilizing effects of single-chromosome aneuploidy may facilitate the development of balanced, high-complexity karyotypes that are frequently found in advanced malignancies.
Reconstruction of ancestral genomes in presence of gene gain and loss
Authors: Avdeyev Pavel , Jiang Shuai , Aganezov Sergey , Hu Fei , Alekseyev Max A.
Published: February 2016

Since most dramatic genomic changes are caused by genome rearrangements as well as gene duplications and gain/loss events, it becomes crucial to understand their mechanisms and reconstruct ancestral genomes of the given genomes. This problem was shown to be NP-complete even in the “simplest” case of three genomes, thus calling for heuristic rather than exact algorithmic solutions. At the same time, a larger number of input genomes may actually simplify the problem in practice as it was earlier illustrated with MGRA, a state-of-the-art software tool for reconstruction of ancestral genomes of multiple genomes.

One of the key obstacles for MGRA and other similar tools is presence of breakpoint reuses when the same breakpoint region is broken by several different genome rearrangements in the course of evolution. Furthermore, such tools are often limited to genomes composed of the same genes with each gene present in a single copy in every genome. This limitation makes these tools inapplicable for many biological datasets and degrades the resolution of ancestral reconstructions in diverse datasets.

We address these deficiencies by extending the MGRA algorithm to genomes with unequal gene contents. The developed next-generation tool MGRA2 can handle gene gain/loss events and shares the ability of MGRA to reconstruct ancestral genomes uniquely in the case of limited breakpoint reuse. Furthermore, MGRA2 employs a number of novel heuristics to cope with higher breakpoint reuse and process datasets inaccessible for MGRA. In practical experiments, MGRA2 shows superior performance for simulated and real genomes as compared to other ancestral genomes reconstruction tools. The MGRA2 tool is distributed as an open-source software and can be downloaded from GitHub repositoryhttp://github.com/ablab/mgra/. It is also available in the form of a web-server athttp://mgra.cblab.org, which makes it readily accessible for inexperienced users.
Fluctuations in populations of subsurface methane oxidizers in coordination with changes in electron acceptor availability
Authors: Magnabosco C. , Timmers P.H.A. , Lau M.C.Y. , Borgonie G. , Linage-Alvarez B. , Kuloyo O. , Alleva R. , Kieft T.L. , Slater G.F. , van Heerden E. , Sherwood Lollar B. , Onstott T.C.
Published: February 2016

The concentrations of electron donors and acceptors in the terrestrial subsurface biosphere fluctuate due to migration and mixing of subsurface fluids, but the mechanisms and rates at which microbial communities respond to these changes are largely unknown. Subsurface microbial communities exhibit long cellular turnover times and are often considered relatively static—generating just enough ATP for cellular maintenance. Here, we investigated how subsurface populations of CH4oxidizers respond to changes in electron acceptor availability by monitoring the biological and geochemical composition in a 1,339 meters-below-land-surface (mbls) fluid-filled fracture over the course of both longer (2.5 year) and shorter (2-week) time scales. Using a combination of metagenomic, metatranscriptomic, and metaproteomic analyses, we observe that the CH4oxidizers within the subsurface microbial community change in coordination with electron acceptor availability over time. We then validate these findings through a series of13C-CH4laboratory incubation experiments, highlighting a connection between composition of subsurface CH4oxidizing communities and electron acceptor availability.
StrainSeeker: fast identification of bacterial strains from unassembled sequencing reads using user-provided guide trees
Authors: Roosaare Märt , Vaher Mihkel , Kaplinski Lauris , Möls Märt , Andreson Reidar , Lepamets Maarja , Kõressaar Triinu , Naaber Paul , Kõljalg Siiri , Remm Maido
Published: February 2016

Background

Fast, accurate and high-throughput detection of bacteria is in great demand. The present work was conducted to investigate the possibility of identifying both known and unknown bacterial strains from unassembled next-generation sequencing reads using custom-made guide trees.

Results

A program named StrainSeeker was developed that constructs a list of specific k-mers for each node of any given Newick-format tree and enables rapid identification of bacterial genomes within minutes. StrainSeeker has been tested and shown to successfully identifyEscherichia colistrains from mixed samples in less than 5 minutes. StrainSeeker can also identify bacterial strains from highly diverse metagenomics samples. StrainSeeker is available athttp://bioinfo.ut.ee/strainseeker.

Conclusions

Our novel approach can be useful for both clinical diagnostics and research laboratories because novel bacterial strains are constantly emerging and their fast and accurate detection is very important.
ZIKA - How Fast Does This Virus Mutate?
Authors: Logan Ian
Published: February 2016

The World Health Organisation has declared the present epidemic of infection with the Zika virus to be a ‘Public Health Emergency of International Concern’. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in foetuses and Guillain-Barré syndrome in some adults.

In this paper the techniques and utilities developed in the study of mitochondrial DNA are applied to the Zika virus. As a result it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured.

The study shows the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10,272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those which are not.
Micro- and macroevolutionary trade-offs in plant-feeding insects
Authors: Peterson Daniel A. , Hardy Nate B. , Normark Benjamin B.
Published: February 2016

A long-standing hypothesis asserts that plant-feeding insects specialize on particular host plants because of negative interactions (trade-offs) between adaptations to alternative hosts, yet empirical evidence for such trade-offs is scarce. Most studies have looked for microevolutionary performance trade-offs within insect species, but host-use could also be constrained by macroevolutionary trade-offs caused by epistasis and historical contingency. On the other hand, evolutionary interactions between adaptations to diverse hosts could be neutral or positive rather than negative. Here we used a phylogenetic approach to estimate the micro-and macroevolutionary correlations between use of alternative host plants within two major orders of plant-feeding insects: Lepidoptera (caterpillars) and Hemiptera (true bugs). Across 1604 caterpillar species, we found both positive and negative pairwise correlations between use of diverse host taxa, with overall network patterns suggesting that different host-use constraints act over micro-and macroevolutionary timescales. In contrast, host-use patterns of 955 true bug species revealed uniformly positive correlations between presence on the same host taxa over both timescales. The lack of consistent patterns across timescales and insect orders indicates that host-use trade-offs are historically contingent rather than universal constraints. Moreover, we observed few negative correlations overall despite the wide taxonomic and ecological diversity of the focal host taxa, suggesting that positive interactions between host-use adaptations, not trade-offs, dominate the long-term evolution of host use in plant-feeding insects.
Do persistent rare species experience stronger negative frequency dependence than common species?
Authors: Yenni Glenda , Adler Peter B. , Ernest S. K. Morgan
Published: February 2016

Understanding why so many species are rare yet persistent remains a significant challenge for both theoretical and empirical ecologists. Yenni, Adler, and Ernest (2012) proposed that strong negative frequency dependence causes species to be rare while simultaneously buffering them against extinction. This hypothesis predicts that, on average, rare species should experience stronger negative frequency dependence than common species. However, it is unknown if ecological communities generally show this theoretical pattern, or if rarity is primarily determined by other processes that overwhelm the effects of strong negative frequency dependence. We discuss the implications of this mechanism for natural communities, and develop a method to test for a non-random relationship between negative frequency dependence and relative abundance, using species abundance data from 90 communities across a broad range of environments and taxonomic groups. To account for biases introduced by measurement error, we compared the observed correlation between species relative abundance and the strength of frequency dependence against expectations from a randomization procedure. In approximately half of the analyzed communities, rare species showed disproportionately strong negative frequency dependence compared to common species. Specifically, we found a pattern of increasingly strong negative frequency dependence with decreasing relative abundance. Our results suggest that strong negative frequency dependence is a signature of both rarity and persistence for many species in many communities.
An ecological assessment of the pandemic threat of Zika virus
Authors: Carlson Colin J. , Dougherty Eric R. , Getz Wayne
Published: February 2016

The current outbreak of Zika virus poses a threat of unknown magnitude to human health1. While the range of the virus has been cataloged growing slowly over the last 50 years, the recent explosive expansion in the Americas indicates that the full potential distribution of Zika remains uncertain2-4. Moreover, most current epidemiology relies on its similarities to dengue fever, a phylogenetically closely related disease of unknown similarity in spatial range or ecological niche5,6. Here we compile the first spatially explicit global occurrence dataset from Zika viral surveillance and serological surveys, and construct ecological niche models to test basic hypotheses about its spread and potential establishment. The hypothesis that the outbreak of cases in Mexico and North America are anomalous and outside the ecological niche of the disease, and may be linked to El Nino or similar climatic events, remains plausible at this time7. Comparison of the Zika niche against the known distribution of dengue fever suggests that Zika is more constrained by the seasonality of precipitation and diurnal temperature fluctuations, likely confining the disease to the tropics outside of pandemic scenarios. Projecting the range of the diseases in conjunction with vector species (Aedes africanus,Ae. aegypti, andAe. albopictus) that transmit the pathogens, under climate change, suggests that Zika has potential for northward expansion; but, based on current knowledge, Zika is unlikely to fill the full range its vectors occupy. With recent sexual transmission of the virus known to have occurred in the United States, we caution that our results only apply to the vector-borne aspect of the disease, and while the threat of a mosquito-carried Zika pandemic may be overstated in the media, other transmission modes of the virus may emerge and facilitate naturalization worldwide.
CRISPR-directed mitotic recombination enables genetic mapping without crosses
Authors: Sadhu Meru J. , Bloom Joshua S. , Day Laura , Kruglyak Leonid
Published: February 2016

Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences.
Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte‐derived Langerhans cells in patients with atopic dermatitis
Authors: Miyano Kyohei , Matsushita Sho , Tsuchida Tetsuya , Nakamura Koichiro
Published: February 2016

We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte‐derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2‐signaled enhancement, peptidoglycan (PGN)‐enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen‐activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T‐helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD.
The wounded blogger: analysis of narratives by women with breast cancer
Authors: Coll‐Planas Gerard , Visa Mariona
Published: February 2016

The purpose of this article is to analyse the representation of the body in seven blogs by Spanish women with breast cancer. Using both texts and images, we analyse how they reproduce modern and postmodern logic to represent the wounded body. Based on Frank's proposals, this article draws the conclusion that the women bloggers mainly reproduce the modern logic (characterised by the restitution narrative and a predictable, disassociated and monadic body), but there are elements which break with this logic (the quest narrative, the body presented as associated, dyadic and full of desire, and the acceptance of contingency). After applying Frank's categories, we suggest that the contemporary way of experiencing illness may question the clarity of the modern/postmodern divide.