bluuebunny/crossref_metadata_2025 huggingface dataset:
Radial velocity confirmation of K2-100b: a young, highly irradiated, and low-density transiting hot Neptune
Authors: Barragán O , Aigrain S , Kubyshkina D , Gandolfi D , Livingston J , Fridlund M C V , Fossati L , Korth J , Parviainen H , Malavolta L , Palle E , Deeg H J , Nowak G , Rajpaul V M , Zicher N , Antoniciello G , Narita N , Albrecht S , Bedin L R , Cabrera J , Cochran W D , de Leon J , Eigmüller Ph , Fukui A , Granata V , Grziwa S , Guenther E , Hatzes A P , Kusakabe N , Latham D W , Libralato M , Luque R , Montañés-Rodríguez P , Murgas F , Nardiello D , Pagano I , Piotto G , Persson C M , Redfield S , Tamura M
Published: September 2019

We present a detailed analysis of HARPS-N radial velocity observations of K2-100, a young and active star in the Praesepe cluster, which hosts a transiting planet with a period of 1.7 d. We model the activity-induced radial velocity variations of the host star with a multidimensional Gaussian Process framework and detect a planetary signal of 10.6 ± 3.0 ${\rm m\, s^{-1}}$, which matches the transit ephemeris, and translates to a planet mass of 21.8 ± 6.2 M⊕. We perform a suite of validation tests to confirm that our detected signal is genuine. This is the first mass measurement for a transiting planet in a young open cluster. The relatively low density of the planet, $2.04 _{ - 0.61 } ^ { + 0.66 }$ ${\rm g\, cm^{-3}}$, implies that K2-100b retains a significant volatile envelope. We estimate that the planet is losing its atmosphere at a rate of $10^{11}\!-\!10^{12}\, {\rm g\, s^{-1}}$ due to the high level of radiation it receives from its host star.
Ground-based observation of ZZ Ceti stars and the discovery of four new variables
Authors: Romero Alejandra D , Amaral L Antunes , Klippel T , Sanmartim D , Fraga L , Ourique G , Pelisoli I , Lauffer G R , Kepler S O , Koester D
Published: September 2019

We perform ground-based photometric observations of 22 DA white dwarf stars, 10 already known ZZ Cetis and 12 candidates with atmospheric parameters inside the classical instability strip. We report on the discovery of four new variable DA white dwarf stars. Two objects are near the middle of the instability strip, SDSS J082804.63+094956.6 and SDSS J094929.09+101918.8, and two red edge pulsators, GD 195 and L495−82. In addition, we classified four objects as possible variables, since evidence of variability was detected in the light curve, but the signal-to-noise ratio was not sufficient to establish a definite detection. Follow-up observations were performed for 10 known ZZ Ceti stars to verify period stability and search for new periodicities. For each confirmed variable, we perform a detailed asteroseismological fit and compare the structural parameters obtained from the best-fitting models with those obtained from spectroscopy and photometry from Gaia. Finally we present a study of the asteroseismological properties of a sample of 91 ZZ Ceti stars.
Oxygen yields as a constraint on feedback processes in galaxies
Authors: Lara-López Maritza A , De Rossi Maria Emilia , Pilyugin Leonid S , Gallazzi Anna , Hughes Thomas M , Zinchenko Igor A
Published: September 2019

We study the interplay between several properties determined from optical and a combination of optical/radio measurements, such as the effective oxygen yield (yeff), the star formation efficiency, gas metallicity, depletion time, gas fraction, and baryonic mass (Mbar), among others. We use spectroscopic data from the SDSS survey, and H i information from the ALFALFA survey to build a statistically significant sample of more than 5000 galaxies. Furthermore, we complement our analysis with data from the GASS and COLD GASS surveys, and with a sample of star-forming galaxies from the Virgo cluster. Additionally, we have compared our results with predictions from the EAGLE simulations, finding a very good agreement when using the high-resolution run. We explore in detail the Mbar–yeff relation, finding a bimodal trend that can be separated when the stellar age of galaxies is considered. On one hand, yeff increases with Mbar for young galaxies [log(tr) < 9.2 yr], while yeff shows an anticorrelation with Mbar for older galaxies [log(tr) > 9.4 yr]. While a correlation between Mbar and yeff has been observed and studied before, mainly for samples of dwarfs and irregular galaxies, their anticorrelated counterpart for massive galaxies has not been previously reported. The EAGLE simulations indicate that AGN feedback must have played an important role in their history by quenching their star formation rate, whereas low-mass galaxies would have been affected by a combination of outflows and infall of gas.
A fast radio burst in the direction of the Virgo Cluster
Authors: Agarwal Devansh , Lorimer Duncan R , Fialkov Anastasia , Bannister Keith W , Shannon Ryan M , Farah Wael , Bhandari Shivani , Macquart Jean-Pierre , Flynn Chris , Pignata Giuliano , Tejos Nicolas , Gregg Benjamin , Osłowski Stefan , Rajwade Kaustubh , Mickaliger Mitchell B , Stappers Benjamin W , Li Di , Zhu Weiwei , Qian Lei , Yue Youling , Wang Pei , Loeb Abraham
Published: September 2019

The rate of fast radio bursts (FRBs) in the direction of nearby galaxy clusters is expected to be higher than the mean cosmological rate if intrinsically faint FRBs are numerous. In this paper, we describe a targeted search for faint FRBs near the core of the Virgo Cluster using the Australian Square Kilometre Array Pathfinder telescope. During 300 h of observations, we discovered one burst, FRB 180417, with dispersion measure (DM) = 474.8 cm−3 pc. The FRB was promptly followed up by several radio telescopes for 27 h, but no repeat bursts were detected. An optical follow-up of FRB 180417 using the PROMPT5 telescope revealed no new sources down to an R-band magnitude of 20.1. We argue that FRB 180417 is likely behind the Virgo Cluster as the Galactic and intracluster DM contribution are small compared to the DM of the FRB, and there are no galaxies in the line of sight. The non-detection of FRBs from Virgo constrains the faint-end slope, α < 1.52 (at 68 per cent confidence limit), and the minimum luminosity, Lmin ≳ 2 × 1040 erg s−1 (at 68 per cent confidence limit), of the FRB luminosity function assuming cosmic FRB rate of 104 FRBs per sky per day with flux above 1 Jy located out to redshift of 1. Further FRB surveys of galaxy clusters with high-sensitivity instruments will tighten the constraints on the faint end of the luminosity function and, thus, are strongly encouraged.
Cell-free expression of RNA encoded genes using MS2 replicase
Authors: Weise Laura I , Heymann Michael , Mayr Viktoria , Mutschler Hannes
Published: September 2019

RNA replicases catalyse transcription and replication of viral RNA genomes. Of particular interest for in vitro studies are phage replicases due to their small number of host factors required for activity and their ability to initiate replication in the absence of any primers. However, the requirements for template recognition by most phage replicases are still only poorly understood. Here, we show that the active replicase of the archetypical RNA phage MS2 can be produced in a recombinant cell-free expression system. We find that the 3′ terminal fusion of antisense RNAs with a domain derived from the reverse complement of the wild type MS2 genome generates efficient templates for transcription by the MS2 replicase. The new system enables DNA-independent gene expression both in batch reactions and in microcompartments. Finally, we demonstrate that MS2-based RNA-dependent transcription-translation reactions can be used to control DNA-dependent gene expression by encoding a viral DNA-dependent RNA polymerase on a MS2 RNA template. Our study sheds light on the template requirements of the MS2 replicase and paves the way for new in vitro applications including the design of genetic circuits combining both DNA- and RNA-encoded systems.
funtrp: identifying protein positions for variation driven functional tuning
Authors: Miller Maximilian , Vitale Daniel , Kahn Peter C , Rost Burkhard , Bromberg Yana
Published: September 2019

Evaluating the impact of non-synonymous genetic variants is essential for uncovering disease associations and mechanisms of evolution. An in-depth understanding of sequence changes is also fundamental for synthetic protein design and stability assessments. However, the variant effect predictor performance gain observed in recent years has not kept up with the increased complexity of new methods. One likely reason for this might be that most approaches use similar sets of gene and protein features for modeling variant effects, often emphasizing sequence conservation. While high levels of conservation highlight residues essential for protein activity, much of the variation observable in vivo is arguably weaker in its impact, thus requiring evaluation at a higher level of resolution. Here, we describe functionNeutral/Toggle/Rheostatpredictor (funtrp), a novel computational method that categorizes protein positions based on the position-specific expected range of mutational impacts: Neutral (weak/no effects), Rheostat (function-tuning positions), or Toggle (on/off switches). We show that position types do not correlate strongly with familiar protein features such as conservation or protein disorder. We also find that position type distribution varies across different protein functions. Finally, we demonstrate that position types can improve performance of existing variant effect predictors and suggest a way forward for the development of new ones.
Characteristics and Long-Term Outcome of 20 Children With Intramedullary Spinal Cord Cavernous Malformations
Authors: Ren Jian , Hong Tao , Zeng Gao , He Chuan , Li Xiaoyu , Ma Yongjie , Yu Jiaxing , Ling Feng , Zhang Hongqi
Published: September 2019

BACKGROUND

No prior reports have focused on the natural history and long-term outcomes of intramedullary spinal cord cavernous malformations (ISCCMs) in children.

OBJECTIVE

To investigate the clinical characteristics and long-term outcomes of pediatric ISCCMs and identify the risk of hemorrhage.

METHODS

We retrospectively reviewed a series of 20 pediatric patients (<18 yr old) from a consecutive series of 254 patients with ISCCMs evaluated at a single institution.

RESULTS

Of the 20 pediatric patients, 9 (45.0%) presented with a severe neurological and disability status. The annual hemorrhagic rate in pediatric patients was 8.2%/patient/year. After initial overt hemorrhage events, the annual overt rehemorrhage rate increased to 30.7%/patient/year. In 234 adult patients, the respective rates were 2.8% and 7.4%. Thoracic or lumbar level lesions (P = .002, OR = 3.425, 95% CI = 1.588-7.387) and rehemorrhagic events (P = .005, OR = 3.209, 95% CI = 1.415-7.279) were more likely to follow an aggressive course. There were no significant differences in the sex distribution, location and size of lesions, types of symptoms, likelihood of a severe neurological and disability status, or immediate and long-term postoperative outcomes between pediatric and adult patients with ISCCMs

CONCLUSION

The annual overt hemorrhage rate and rehemorrhage rate of ISCCMs were higher in affected children than in affected adults. Surgical resection of pediatric ISCCMs remains the preferred therapeutic option and provides favorable outcomes.
The Ruptured Arteriovenous Malformation Grading Scale (RAGS): An Extension of the Hunt and Hess Scale to Predict Clinical Outcome for Patients With Ruptured Brain Arteriovenous Malformations
Authors: Silva Michael A , Lai Pui Man Rosalind , Du Rose , Aziz-Sultan Mohammad A , Patel Nirav J
Published: September 2019

BACKGROUND

Arteriovenous malformation (AVM) rupture is highly morbid. Outcomes after AVM rupture differ from other types of brain hemorrhage. There are no specific widely used grading systems designed to predict clinical outcome after AVM rupture.

OBJECTIVE

To develop an all-comers scoring system to grade patients with AVM rupture and predict clinical outcome more accurately than grading systems currently in use.

METHODS

We retrospectively reviewed patients who presented to our institution with a ruptured AVM. Using change in modified Rankin Score (mRS) as our response variable, we generated an ordinal logistic regression model to test for significant predictor variables. The full model was sequentially condensed until the simplest model with the highest area under the receiver operating curve (AUROC) was achieved.

RESULTS

A total of 115 patients who presented with ruptured AVMs were included in the study, with a mean follow-up time of 4 yr. The Ruptured AVM Grading Scale (RAGS) consists of the Hunt and Hess (HH) score (1-5), patient age (<35 = 0, 35-70 = 1, and >70 = 2), deep venous drainage (1), and eloquence (1). The RAGS score outperformed other neurosurgical grading scales in predicting change in mRS, with an AUROC greater than 0.80 across all follow-up periods.

CONCLUSION

The RAGS score is a simple extension of the HH scale that predicts clinical outcome after AVM rupture more accurately than other grading systems.
Jasmonates-Mediated Rewiring of Central Metabolism Regulates Adaptive Responses
Authors: Savchenko Tatyana V , Rolletschek Hardy , Dehesh Katayoon
Published: September 2019

The lipid-derived hormones jasmonates (JAs) play key functions in a wide range of physiological and developmental processes that regulate growth, secondary metabolism and defense against biotic and abiotic stresses. In this connection, biosynthesis, tissue-specific distribution, metabolism, perception, signaling of JAs have been the target of extensive studies. In recent years, the involvement of JAs signaling pathway in the regulation of growth and adaptive responses to environmental challenges has been further examined. However, JAs-mediated mechanisms underlying the transition from ‘growth mode’ to ‘adaptive mode’ remain ambiguous. Combined analysis of transgenic lines deficient in JAs signaling in conjunction with the data from JAs-treated plants revealed the function of these hormones in rewiring of central metabolism. The collective data illustrate JAs-mediated decrease in the levels of metabolites associated with active growth such as sucrose, raffinose, orotate, citrate, malate, and an increase in phosphorylated hexoses, responsible for the suppression of growth and photosynthesis, concurrent with the induction of protective metabolites, such as aromatic and branched-chain amino acids, and aspartate family of metabolites. This finding provides an insight into the function of JAs in shifting the central metabolism from the production of growth-promoting metabolites to protective compounds and expands our understanding of the role of JAs in resource allocation in response to environmental challenges.
Impact of perceptions of body size on obesity and weight management behaviour: a large representative population study in an African setting
Authors: Chigbu C O , Aniebue U U , Berger U , Parhofer K G
Published: September 2019

Background

Perception of body size is an important psycho-cultural cause of obesity with wide racial and ethnic variations.

Method

Cross-sectional household survey using multistage cluster-randomised sampling. Prevalence estimates were weighted. Logistic regressions were done to determine the impact of perception of large body size on obesity and the impact of perception of own body size on weight-management behaviour. Adjusted odds ratios (AOR) were reported.

Results

The survey involved 6628 adults from 2843 households. More than a quarter of the population is either obese or overweight. Nearly half, 44.07% (95% confidence interval [CI]: 42.48–45.66%) of the population perceive large body size as desirable. Positive perception of large body size significantly increases the odds of obesity by 1.5 (AOR: 1.45; 95% CI: 1.09–1.9). Some 42.03% (95% CI: 35.52–48.55%) obese persons misperceive their weight to be normal. Perceiving own body size as normal decreases the odds of weight-losing behaviour (AOR: 0.019; 95% CI: 0.014–0.026).

Conclusion

There is a high level of veneration of large body size in southeast Nigeria, and this has a significant impact on obesity burden. Perception of own body size has a significant impact on weight-management behaviour. Health-promotion policies aimed at changing the social desirability of large body size and misperception of body size are recommended.
Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years
Authors: Möller Burkhard , Aletaha Daniel , Andor Michael , Atkinson Andrew , Aubry-Rozier Bérengère , Brulhart Laure , Dan Diana , Finckh Axel , Grobéty Véronique , Mandl Peter , Micheroli Raphael , Nissen Michael John , Nydegger Alexander M , Scherer Almut , Tamborrini Giorgio , Ziswiler Hans-Rudolf , Zufferey Pascal ,   and the SONAR group for musculoskeletal ultrasound in the Swiss Clinical Quality Management (SCQM) Foundation
Published: September 2019

Objectives

To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA.

Methods

In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders.

Results

After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup.

Conclusion

Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.
Phosphorylation-related SNPs influence lipid levels and rheumatoid arthritis risk by altering gene expression and plasma protein levels
Authors: Mo Xingbo , Guo Yufan , Qian Qiyu , Fu Mengzhen , Zhang Huan
Published: September 2019

Objectives

Phosphorylation-related single-nucleotide polymorphisms (phosSNPs) are missense SNPs that may influence protein phosphorylation. The aim of this study was to evaluate the effect of phosSNPs on lipid levels and RA.

Methods

We examined the association of phosSNPs with lipid levels and RA in large-scale genome-wide association studies (GWAS) and performed random sampling and fgwas analyses to determine whether the phosSNPs associated with lipid levels and RA were significantly enriched. Furthermore, we performed QTL analysis and Mendelian randomization analysis to obtain additional evidence to be associated with the identified phosSNPs and genes.

Results

We found 483 phosSNPs for lipid levels and 243 phosSNPs for RA in the GWAS loci (P < 1.0 × 10−5). SNPs associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Total cholesterol (TC) and RA were significantly enriched with phosSNPs. Almost all of the identified phosSNPs showed expression quantitative trait loci (eQTL) effects. A total of 48 protein QTLs and 9 metabolite QTLs were found. The phosSNP rs3184504 (p.Trp262Arg) at SH2B3 was significantly associated with RA, SH2B3 expression level, and plasma levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC, hypoxanthine and 80 proteins, including beta-2-microglobulin. SH2B3 was differentially expressed between RA cases and controls in peripheral blood mononuclear cells and synovial tissues. Mendelian randomization analysis showed that SH2B3 expression level was significantly associated with TC level and RA. Plasma beta-2-microglobulin level was causally associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TC levels and RA.

Conclusion

The findings suggested that phosSNPs may play important roles in lipid metabolism and the pathological mechanisms of RA. PhosSNPs may influence lipid levels and RA risk by altering gene expression and plasma protein levels.
‘It can’t be zero!’ Difficulties in completing patient global assessment in rheumatoid arthritis: a mixed methods study
Authors: Ferreira Ricardo J O , de Wit Maarten , Henriques Marta , Pinto Ana F , Duarte Cátia , Mateus Elsa , Mendes Gabriel , da Silva José A P , Ndosi Mwidimi
Published: September 2019

Objectives

Patient global assessment (PGA) is purported to add the patient’s perspective in the composite measures of RA. However, PGA is not standardized and it is not known whether patients’ interpretation of the measure is consistent with its intended purpose. This study aimed to explore difficulties experienced by patients with RA in completing PGA, and to assess the impact of a structured explanation in improving its validity and reliability.

Methods

This was a mixed methods study, using interviews, focus groups and PGA data. During interviews, patients (convenience sample, n = 33) completed three often-used PGA formulations. Then a nurse provided structured explanation about what PGA is and why it is used. After further discussion, patients completed one PGA version again. Interviews were recorded, transcribed and analysed using inductive thematic analysis. We compared PGA scores pre- and post-explanation (Wilcoxon signed-ranks) and the proportion of patients achieving RA remission with PGA ⩽1 (McNemar’s tests).

Results

Three themes emerged: understanding the meaning of PGA, the purpose of PGA and measurement difficulties. The difficulties caused systematic errors in PGA completion such as marking higher when feeling well, marking near the centre or away from zero. The structured explanation was helpful. Following the explanation, the median PGA score decreased from 3.0 to 2.1 cm, and the proportion of non-remission solely due to PGA >1 from 52% to 41%; none of these changes was statistically significant.

Conclusion

Many patients have difficulties in completing PGA. Standardization of PGA and a structured explanation may improve its clarity, validity and reliability.
The effects of long non-coding ribonucleic acids on various cellular components in rheumatoid arthritis
Authors: Fang Yilong , Tu Jiajie , Han Dafei , Guo Yawei , Hong Wenming , Wei Wei
Published: September 2019

RA is a chronic, autoimmune-mediated inflammatory pathology. Long non-coding RNAs (lncRNAs) are a novel group of non-coding RNAs with a length of >200 nucleotides. There are reports emerging that suggest that lncRNAs participate in establishing and sustaining autoimmune diseases, including RA. In this review article, we highlight the functions of lncRNAs in different cell types in RA. Our review indicates that lncRNAs affect various cellular components and are novel candidates that could constitute promising targets for the diagnosis and treatment of RA.
The Racialized Nature of Child Welfare Policies and the Social Control of Black Bodies
Authors: Harp Kathi L H , Bunting Amanda M
Published: September 2019

Black women are disproportionately involved in the child welfare system. This state-level intervention occurs at two levels—a higher likelihood of being (i) screened for drug use during pregnancy and (ii) reported to child welfare authorities after delivery. Consequently, they face further enmeshment in state-systems, including custody loss and lower reunification odds. Using evidence from the past forty years of research and media reports, we argue that systemic forces and policies largely contribute to racial disproportionality in the child welfare system, and assert this state intervention serves as a mechanism to control black reproduction.
Publicizing the (In)visible? Celebrities, Anti-Human Trafficking Activism, and Feminist Ideologies
Authors: Majic Samantha
Published: September 2019

This article examines celebrities’ anti-human trafficking activism from 2000 to 2016 to interpret how they use their fame and personal experiences to publicize feminist issues. Drawing from an original dataset, I argue first that celebrities represent human trafficking in ways that circulate various feminist ideologies. Next, I juxtapose Ashley Judd and Jada Pinkett Smith to examine how individual celebrities adopt, reflect, and complicate these representations and ideologies, arguing here that celebrities variously deploy their personal stories to challenge and reinforce race and gender hierarchies. The conclusion considers this research’s broader implications for understanding celebrities, feminism, and policy debates.
The Spiritual Challenges Faced by Family Caregivers of Patients With Cancer
Authors: Nemati Shahnaz , Rassouli Maryam , ilkhani Mahnaz , Baghestani Ahmad Reza
Published: September 2019

This qualitative study was conducted to investigate the spiritual challenges faced by Iranian family caregivers of patients with cancer. The findings showed, 2 main themes, including “spiritual crisis” and “spiritual coherence”, and 6 classes, including “spiritual distress”, “disappointment,” “faith and trust in God,” “praying,” “inner peace,” and “transcendence.”
A Synthesis of Coping Experiences After Infant Death
Authors: Stiffler Deborah , Birch Nicole , Campbell Hailey , Cullen Deborah
Published: September 2019

The purpose of this article was to synthesize qualitative research data that examine parental coping strategies following infant death. This qualitative synthesis found that parents who effectively cope with the death of their infant would continue the bond with the deceased child, have differences in the way they manage their emotions about the loss, and have intergenerational support in the form of family being present, acknowledging the death, performing immediate tasks, and providing helpful information. Nurses should be vigilant to ensure parents receive “memories” of their infant after an in-hospital death. Knowledge of the coping process can assist nurses and clinicians to better care and support parents following an infant death and, in turn, facilitate the healing process.
Ureteral Stents
Authors: Ucuzal Meral , Serçe Perihan
Published: September 2019

Ureteral stents have an indispensable place in urology, and indications for their use are increasing. However, stents can affect their users' quality of life negatively because of complications and adverse effects. This descriptive research aimed to determine the effect of ureteral stenting on quality of life. The study sample consisted of 75 patients. Data were collected using a questionnaire form, the SF-36 Quality of Life Scale, and the International Prostate Symptom Score. Patients were interviewed twice (before stenting and 1 month after stenting). The data were analyzed with descriptive statistics methods. This research determined that patients with ureteral stents had increased lower urinary tract symptoms and significantly reduced quality of life.
Case Report: Corneal Ulceration from Bilateral Ectropion Due to Congenital Ichthyosis
Authors: Vollmer Lori , Sowka Joseph
Published: September 2019

SIGNIFICANCE

Ichthyosis is a group of heterogenous inherited skin disorders characterized by abnormal cornification and keratinization of the skin. Autosomal recessive congenital ichthyosis presents with severe lagophthalmos and cicatricial ectropion of both upper and lower lids. Chronic corneal exposure from lid abnormalities may lead to ulcerative keratitis or corneal perforation.

PURPOSE

The case highlights a rarely seen condition that presents with potentially serious ocular complications and vision loss. Corneal complications may be avoided or managed with moisture goggles, corneal vaulting with scleral lenses, topical therapeutics, amniotic membrane, and surgical lid repair.

CASE REPORT

A 25-year-old woman presented with a painful right eye for 1 week. She had a medical history of autosomal recessive congenital ichthyosis. Her ocular adnexa revealed bilateral lagophthalmos and cicatricial ectropion of both upper and lower lids. The slit lamp of examination revealed an injected eye with corneal ulcer with hypopyon in the right eye and quiet eye with corneal scarring in the left eye. The patient was treated with topical moxifloxacin and polymyxin B sulfate/trimethoprim as well as in-office homatropine 5% in the right eye. The keratitis was treated to resolution, and the patient referred for consultation on lid repair.

CONCLUSIONS

Chronic corneal exposure from autosomal recessive congenital ichthyosis may lead to severe dry eye, ulcerative keratitis, or perforation. Patients should be monitored carefully for corneal disease, educated on methods and devices to protect the corneal surface, and referred for surgical repair if indicated. Although rare, this condition presents unique findings that may be visually devastating. Awareness of the condition, as well as the various clinical presentations and appropriate management necessary, will prove beneficial to the patient.
Application of Topographical Keratoconus Detection Metrics to Eyes of Individuals with Down Syndrome
Authors: Marsack Jason D. , Benoit Julia S. , Kollbaum Pete S. , Anderson Heather A.
Published: September 2019

SIGNIFICANCE

The challenges associated with clinical assessment of individuals with Down syndrome contribute to a wide range of estimates on the prevalence of keratoconus in the Down syndrome population. This work focuses on two topographical indices previously identified with keratoconus detection, applying them to a topographical data set meeting strict sampling criteria.

PURPOSE

The purpose of this study was to quantify the level of keratoconus-like topographical morphology in a large sample of eyes from individuals with Down syndrome, as identified by two keratoconus detection metrics: inferior-superior dioptric asymmetry (I-S) and KISA%. Severity of the asymmetry was also cast within the context of established Collaborative Longitudinal Evaluation of Keratoconus study disease severity classification criteria.

METHODS

Corneal topography data on both eyes of 140 subjects with Down syndrome and 138 control subjects were collected. Both I-S and KISA% were calculated from the topography data of eyes with sufficient sampling. Steep and flat keratometry data are reported for subjects with measurements on both eyes in the context of values recorded by the Collaborative Longitudinal Evaluation of Keratoconus study in frank keratoconus to examine within-eye and between-eye asymmetry and severity.

RESULTS

Keratoconus detection thresholds were exceeded in 20.8% of the eyes of subjects with Down syndrome and 2.2% of the eyes of controls using I-S and 11.8% of the eyes of subjects with Down syndrome and 0.0% of the eyes of controls using KISA%. Examination of the level of intraeye difference between flat and steep keratometry data for individuals with Down syndrome detected as having corneal morphology consistent with moderate keratoconus yields an average of 1.81 D of toricity, whereas the Collaborative Longitudinal Evaluation of Keratoconus study reported 3.28 D of toricity.

CONCLUSIONS

Morphology consistent with keratoconus as codified in the detection metrics I-S and KISA% is present in a large percentage of the eyes of individuals with Down syndrome. Differences were observed in the distribution of severity of corneal morphology in individuals with Down syndrome and the keratoconus population at large.
Establishing the role of SINE proteins in regulating stomatal dynamics in Arabidopsis thaliana
Authors: Biel Alecia , Moser Morgan , Meier Iris
Published: September 2019

Stomatal movement, which regulates gas exchange in plants, is controlled by a variety of environmental factors, including biotic and abiotic stresses. The stress hormone ABA initiates a signaling cascade, which leads to increased H2O2 and Ca2+ levels and F-actin reorganization, but the mechanism of, and connection between, these events is unclear. SINE1, an outer nuclear envelope component of a plant Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, associates with F-actin and is, along with its paralog SINE2, expressed in guard cells. Here, we have determined that Arabidopsis SINE1 and SINE2 play an important role in stomatal regulation. We show that SINE1 and SINE2 are required for stomatal opening and closing. Loss of SINE1 or SINE2 results in ABA hyposensitivity and impaired stomatal dynamics but does not affect stomatal closure induced by the bacterial elicitor flg22. The ABA-induced stomatal closure phenotype is, in part, attributed to impairments in Ca2+ and F-actin regulation. Together, the data suggest that SINE1 and SINE2 act downstream of ABA but upstream of Ca2+ and F-actin. While there is a large degree of functional overlap between the two proteins, there are also critical differences. Our study makes an unanticipated connection between stomatal regulation and a novel class of nuclear envelope proteins, and adds two new players to the increasingly complex system of guard cell regulation.
Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes
Authors: Kurd Nadia S. , Hoover Ashley , Yoon Jaewon , Weist Brian M. , Robey Ellen A.
Published: September 2019

Thymocytes bearing αβ T cell receptors (TCRαβ) with high affinity for self-peptide-MHC complexes undergo negative selection or are diverted to alternate T cell lineages, a process termed agonist selection. Among thymocytes bearing TCRs restricted to MHC class I, agonist selection can lead to the development of precursors that can home to the gut and give rise to CD8αα-expressing intraepithelial lymphocytes (CD8αα IELs). The factors that influence the choice between negative selection versus CD8αα IEL development remain largely unknown. Using a synchronized thymic tissue slice model that supports both negative selection and CD8αα̣IEL development, we show that the affinity threshold for CD8αα IEL development is higher than for negative selection. We also investigate the impact of peptide presenting cells and cytokines, and the migration patterns associated with these alternative cell fates. Our data highlight the roles of TCR affinity and the thymic microenvironments on T cell fate.
Escalating protein supersaturation underlies inclusion formation in muscle proteinopathies
Authors: Ciryam Prajwal , Antalek Matthew , Cid Fernando , Tartaglia Gian Gaetano , Dobson Christopher M. , Guttsches Anne-Katrin , Eggers Britta , Vorgerd Matthias , Marcus Katrin , Kley Rudolf A. , Morimoto Richard I. , Vendruscolo Michele , Weihl Conrad
Published: September 2019

Abundant, aggregation prone or “supersaturated” proteins are a feature of neurodegeneration. Whether the principle of supersaturation can similarly explain the widespread aggregation that occurs in non-neuronal protein conformational disorders and underlies pathogenic protein aggregate formation is not established. To test this prediction we analyzed proteomic datasets of biopsies from genetic and acquired protein aggregate myopathy (PAM) patients by quantifying the changes in composition, concentration and aggregation propensity of proteins in the fibers containing inclusions and those surrounding them. We found that similar to neurodegeneration, a supersaturated subproteome of aggregate prone proteins is present in skeletal muscle from healthy patients. This subproteome escalates in degree of supersaturation as proteomic samples are taken more proximal to the pathologic inclusion, eventually exceeding its solubility limits and aggregating. While most supersaturated proteins decrease or maintain steady abundance across healthy fibers and inclusion containing fibers, supersaturated proteins within the aggregate subproteome rise in abundance, suggesting they escape normal regulation. We show in the context of a human conformational disorder that the level of supersaturation of a metastable subproteome helps to explain widespread aggregation and correlates with the histopathological state of the tissue.

Significance

Increasing evidence implicates the phenomenon of protein supersaturation with the selective vulnerability of specific cells to protein misfolding disorders. Quantitative studies of this phenomenon, however, have only been possible post mortem in the case of neurodegenerative diseases. To overcome this limitation, we study here protein aggregate myopathies (PAMs), for which we were able to carry out systematic single fiber proteomic studies on patient-derived samples. We found not only that proteins associated with PAM inclusions are highly supersaturated in muscle but also that their supersaturation levels increases further in affected fibers. These results provide a clear illustration of how an escalation in supersaturation leads protein inclusions in vulnerable cells.
An environmental DNA tool for monitoring the status of the Critically Endangered Smalltooth Sawfish, Pristis pectinata, in the Western Atlantic
Authors: Lehman Ryan N. , Poulakis Gregg R. , Scharer Rachel M. , Schweiss Katherine E. , Hendon Jill M. , Phillips Nicole M.
Published: September 2019

The Critically Endangered Smalltooth Sawfish, Pristis pectinata, was once widespread in the tropical and subtropical waters of the Atlantic Ocean, but following substantial declines over the past century, the core population is currently confined to southwest Florida in the U.S. and the Bahamas. Recent research and verified public encounter reports suggests that this core population may be stabilizing and, potentially, expanding into formerly occupied areas of their historic range in the Western Atlantic; however, the status of this species in non-core waters is not well understood. Environmental DNA (eDNA) methods provide a relatively cost effective and rapid assessment tool for monitoring species occurrence in aquatic habitats. Here, we have developed an eDNA tool: a species-specific Droplet Digital™ PCR (ddPCR™) assay targeting a 100-base pair portion of the mitochondrial NADH dehydrogenase subunit 2 gene in P. pectinata, with the ability to reliably detect as little as 0.25 pg of target DNA. The assay was validated by collecting and analyzing a water sample from known P. pectinata nursery habitat in Florida, which was found to contain an average of 11.54 copies of target DNA/µL (SE = 0.72) in the reaction. The assay was then further tested by placing a juvenile sawfish in an ex situ tank and analyzing water samples collected at time intervals. The implementation of this eDNA tool into field surveys will provide additional, reliable data to assess species recovery and aid in prioritizing localities beyond the core range in which to focus research and education initiatives.
Application of long-interval paired-pulse transcranial magnetic stimulation to motion-sensitive visual cortex does not lead to changes in motion perception
Authors: Arana Olga Lucia Gamboa , Brito Alexandra , Abzug Zachary , D’Arbeloff Tracy , Beynel Lysianne , Wing Erik A. , Dannhauer Moritz , Palmer Hannah , Hilbig Susan A. , Crowell Courtney A. , Donaldson Rachel , Cabeza Roberto , Davis Simon W. , Peterchev Angel V. , Sommer Marc A. , Appelbaum Lawrence G.
Published: September 2019

The perception of visual motion is dependent on a set of occipitotemporal regions which are readily accessible to neuromodulation. Previous studies using paired-pulse Transcranial Magnetic Stimulation (ppTMS) have provided evidence of the capacity of this type of protocols to modulate cognitive processes. To test whether such cortical modulation can be observed in the visual system, particularly during motion perception, ppTMS was applied to the occipital cortex using both scalp-based and meta-analytic targeting coordinates. In this within-subject, sham-controlled study, fifteen subjects completed two sessions in two consecutive weeks. On the first visit, subject-specific resting motor threshold (RMT) was determined and participants performed an adaptive motion discrimination task to determine individual motion sensitivity. During the second visit, subjects performed the same task with three individualized difficulty levels as two TMS pulses were delivered respectively −150 and −50 ms prior to motion stimulus onset at 120% RMT, under the logic that the cumulative inhibitory effect of these two pulses would alter motion sensitivity as measured by the individually calibrated task. The ppTMS was delivered at one of two locations: 3 cm dorsal and 5 cm lateral to inion (scalp-based coordinate), or at the site of peak activation for “motion” according to the NeuroSynth fMRI database (meta-analytic coordinate). Sham stimulation was delivered on one-third of trials and evenly between the two targets. Analyses showed no significant active-versus-sham effects of ppTMS when stimulation was delivered to the meta-analytic (p = 0.15) or scalp-based coordinates (p = 0.17), which were separated by 29 mm on average. Additionally, there was no was significant interaction between ppTMS at either location and task difficulty level (p = 0.12 and p = 0.33, respectively). These findings fail to support the hypothesis that long-interval ppTMS recruits inhibitory processes in motion-sensitive cortex, but must be considered within the limits of the current design choices.

HIGHLIGHTS

Long-interval paired-pulse TMS was applied to visual cortex during a motion task

The ppTMS was delivered according to scalp and meta-analytic coordinates, as well as sham

No effects of active-versus-sham stimulation were observed on motion task performance
Dynamic reversal of random X-Chromosome inactivation during iPSC reprogramming
Authors: Janiszewski Adrian , Talon Irene , Chappell Joel , Collombet Samuel , Song Juan , De Geest Natalie , To San Kit , Bervoets Greet , Marin-Bejar Oskar , Provenzano Caterina , Vanheer Lotte , Marine Jean-Christophe , Rambow Florian , Pasque Vincent
Published: September 2019

Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis, and the derivation of induced pluripotent stem cells (iPSCs). X-Chromosome inactivation (XCI) and reactivation (XCR) in female cells represent chromosome-wide transitions between active and inactive chromatin states. Although XCI has long been studied, providing important insights into gene regulation, the dynamics and mechanisms underlying the reversal of stable chromatin silencing of X-linked genes are much less understood. Here, we use allele-specific transcriptomics to study XCR during mouse iPSC reprogramming in order to elucidate the timing and mechanisms of chromosome-wide reversal of gene silencing. We show that XCR is hierarchical, with subsets of genes reactivating early, late, and very late during reprogramming. Early genes are activated before the onset of late pluripotency genes activation. Early genes are located genomically closer to genes that escape XCI, unlike genes reactivating late. Early genes also show increased pluripotency transcription factor (TF) binding. We also reveal that histone deacetylases (HDACs) restrict XCR in reprogramming intermediates and that the severe hypoacetylation state of the inactive X Chromosome (Xi) persists until late reprogramming stages. Altogether, these results reveal the timing of transcriptional activation of monoallelically repressed genes during iPSC reprogramming, and suggest that allelic activation involves the combined action of chromatin topology, pluripotency TFs, and chromatin regulators. These findings are important for our understanding of gene silencing, maintenance of cell identity, reprogramming, and disease.
Controllability of cupric particle synthesis by linear alcohol chain number as additive and pH control in cupric acetate solution using X-ray radiolysis
Authors: Yamaguchi Akinobu , Okada Ikuo , Sakurai Ikuya , Izumi Hirokazu , Ishihara Mari , Fukuoka Takao , Suzuki Satoru , Elphick Kelvin , Jackson Edward , Hirohata Atsufumi , Utsumi Yuichi
Published: September 2019

Synthesis and immobilization of caltrop cupric particles onto a Si substrate using X-ray radiolysis directly from a liquid solution of Cu(COOCH3)2is demonstrated. Caltrop cupric oxide particles are formed in the X-ray radiolysis of aqueous solutions of Cu(COOCH3)2, which also contain methanol, ethanol, 2-propanol or 1-propanol as ^\bulletOH scavenger. The blade lengths of the caltrop particles are dependent on the alcohol chain length. In particular, it was found that an alkyl alcohol whose chain length is longer than four is unable to synthesize any particles in aqueous solutions of Cu(COOCH3)2in X-ray radiolysis. These results are attributed to the alkyl alcohol chain length influencing the rate of reaction of radicals and determines the solvable ratio of its alcohol into water. In addition, it was found that the synthesized particle geometric structure and composition can also be controlled by the pH of the aqueous solution in the X-ray radiolysis. This study may open a door to understanding and investigating a novel photochemical reaction route induced under X-ray irradiation. The development of the X-ray radiolysis process enables us to achieve the rapid and easy process of synthesis and immobilization of higher-order nano/microstructure consisting of various materials.
3,3-Bis(2-hydroxyethyl)-1-(4-methylbenzoyl)thiourea: crystal structure, Hirshfeld surface analysis and computational study
Authors: Tan Sang Loon , Azizan Ainnul Hamidah Syahadah , Jotani Mukesh M. , Tiekink Edward R. T.
Published: September 2019

In the title tri-substituted thiourea derivative, C13H18N2O3S, the thione-S and carbonyl-O atoms lie, to a first approximation, to the same side of the molecule [the S—C—N—C torsion angle is −49.3 (2)°]. The CN2S plane is almost planar (r.m.s. deviation = 0.018 Å) with the hydroxyethyl groups lying to either side of this plane. One hydroxyethyl group is orientated towards the thioamide functionality enabling the formation of an intramolecular N—H...O hydrogen bond leading to anS(7) loop. The dihedral angle [72.12 (9)°] between the planes through the CN2S atoms and the 4-tolyl ring indicates the molecule is twisted. The experimental molecular structure is close to the gas-phase, geometry-optimized structure calculated by DFT methods. In the molecular packing, hydroxyl-O—H...O(hydroxyl) and hydroxyl-O—H...S(thione) hydrogen bonds lead to the formation of a supramolecular layer in theabplane; no directional interactions are found between layers. The influence of the specified supramolecular interactions is apparent in the calculated Hirshfeld surfaces and these are shown to be attractive in non-covalent interaction plots; the interaction energies point to the important stabilization provided by directional O—H...O hydrogen bonds.
The crystal structure of ((cyclohexylamino){(Z)-2-[(E)-5-methoxy-3-nitro-2-oxidobenzylidene-κO]hydrazin-1-ylidene-κN
2}methanethiolato-κS)(dimethyl sulfoxide-κS)platinum(II): a supramolecular two-dimensional network
Authors: Arafath Md. Azharul , Kwong Huey Chong , Adam Farook
Published: September 2019

The PtII atom in the title complex, [Pt(C15H18N4O4S)(C2H6OS)], exists within a square-planar NS2O donor set provided by the N, S, O atoms of the di-anionic tridentate thiosemicarbazo ligand and a dimethyl sulfoxide S atom. The two chelate rings are coplanar, subtending a dihedral angle of 1.51 (7)°. The maximum deviation from an ideal square-planar geometry is seen in the five-membered chelate ring with an S—Pt—S bite angle of 96.45 (2)°. In the crystal, molecules are linked via N—H...O, C—H...O, C—H...N and C—H...π interactions into two-dimensional networks lying parallel to the ab plane. The conformations of related cyclohexylhydrazine-1-carbothioamide ligands are compared to that of the title compound.