bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved retention of phosphorus donors in germanium using a non-amorphizing fluorine co-implantation technique
Authors: Monmeyran Corentin , Crowe Iain F. , Gwilliam Russell M. , Heidelberger Christopher , Napolitani Enrico , Pastor David , Gandhi Hemi H. , Mazur Eric , Michel Jürgen , Agarwal Anuradha M. , Kimerling Lionel C.
Published: November 2017

Co-doping with fluorine is a potentially promising method for defect passivation to increase the donor electrical activation in highly doped n-type germanium. However, regular high dose donor-fluorine co-implants, followed by conventional thermal treatment of the germanium, typically result in a dramatic loss of the fluorine, as a result of the extremely large diffusivity at elevated temperatures, partly mediated by the solid phase epitaxial regrowth. To circumvent this problem, we propose and experimentally demonstrate two non-amorphizing co-implantation methods; one involving consecutive, low dose fluorine implants, intertwined with rapid thermal annealing and the second, involving heating of the target wafer during implantation. Our study confirms that the fluorine solubility in germanium is defect-mediated and we reveal the extent to which both of these strategies can be effective in retaining large fractions of both the implanted fluorine and, critically, phosphorus donors.
Tunable actuation of dielectric elastomer by electromechanical loading rates
Authors: Li Guorui , Zhang Mingqi , Chen Xiangping , Yang Xuxu , Wong Tuck-Whye , Li Tiefeng , Huang Zhilong
Published: November 2017

Dielectric elastomer (DE) membranes are able to self-deform with the application of an electric field through the thickness direction. In comparison to conventional rigid counterparts, soft actuators using DE provide a variety of advantages such as high compliance, low noise, and light weight. As one of the challenges in the development of DE actuating devices, tuning the electromechanical actuating behavior is crucial in order to achieve demanded loading paths and to avoid electromechanical failures. In this paper, our experimental results show that the electromechanical loading conditions affect the actuating behaviors of the DE. The electrical actuating force can be tuned by 29.4% with the control of the electrical charging rate. In addition, controllable actuations have been investigated by the mechanical model in manipulating the electromechanical loading rate. The calculated results agree well with the experimental data. Lastly, it is believed that the mechanisms of controlling the electromechanical loading rate may serve as a guide for the design of DE devices and high performance soft robots in the near future.
Magnetic compensation-induced sign reversal of exchange bias in a multi-glass perovskite SmFeO3
Authors: De Chandan , Nayak Ajaya K. , Nicklas Michael , Sundaresan A.
Published: November 2017

We report an unusual sign reversal of exchange bias (EB) across a magnetic compensation point in an orthorhombic perovskite SmFeO3. A conventional negative EB with a positive vertical magnetization shift is observed below a cluster-glass freezing temperature (Tg ∼ 150 K). Upon further lowering of the temperature, the EB disappears at the magnetic compensation point before reversing its sign to a positive exchange bias below 4 K. The EB effect originates from an interfacial exchange interaction within a cluster glass phase, whereas its sign reversal arises from the reversal of the direction of the net magnetic moment as a result of dominance of Sm3+ over Fe3+ below the compensation temperature. The existence of a multi-glass state is demonstrated by ac-susceptibility and electrical permittivity measurements. A phenomenological model is presented to understand the EB effect and its sign reversal across the compensation point.
Zinc-based field effect transistors get performance boost from clever engineering
Authors: Kim Mark H.
Published: November 2017

Adding a fourth component offers charge concentration properties to zinc oxide-based field effect transistors that bring them closer to yet-unachieved theoretical limits of performance.
The movement of humans and the spread of Salmonella into existing and pristine ecosystems
Authors: Iveson John B , Bradshaw S Donald , Smith David W
Published: November 2017

The spread of infectious diseases by the international and national movement of people, animals, insects and products has a documented history dating back several centuries1. The role of human movements has been fundamental to this, and has increased as global travel has risen in amount and speed. This has been exemplified by international epidemics of influenza, antimicrobial resistant bacteria, SARS coronavirus, dengue, chikungunya virus, Zika viruses and many others. Foodborne pathogens have also regularly come to our attention for their ability to move internationally, and outbreaks of salmonellosis due to importation of contaminated foods are well described2,3. An extensive collection of non-typhoidal Salmonella and related species isolated from human, food, animal and environmental sources has been accumulated within Western Australia (WA) since the mid-20th century, and has proven an important historical source of information about the role of humans in the dissemination of microorganisms across and within diverse ecosystems4–6. It is clear that the movement of microorganisms into and out of Australia is by no means a new phenomenon, and that humans have been important contributors to that spread. These are important markers of our impact on established and pristine ecosystems.
Sequences flanking the transmembrane segments facilitate mitochondrial localization and membrane fusion by mitofusin
Authors: Huang Xiaofang , Zhou Xin , Hu Xiaoyu , Joshi Amit S. , Guo Xiangyang , Zhu Yushan , Chen Quan , Prinz William A. , Hu Junjie
Published: November 2017

Significance

Mitochondria constantly connect through membrane fusion. The merging of the outer mitochondrial membrane requires mitofusin (MFN) proteins. MFN is a membrane-anchored GTPase, but whether it is sufficient to achieve fusion, and if so how, is largely unknown. We have taken advantage of a similar GTPase named atlastin (ATL), which mediates fusion of the endoplasmic reticulum (ER), as its mechanism is better understood. Domain swapping experiments show that MFN is capable of fusing membranes, even on the ER. The C-terminal tail of MFN contains an amphipathic helix that promotes fusion. MFN is properly inserted into the mitochondrial membrane with the help of the helix and neighboring hydrophobic residues. These findings provide insight into how mitochondria fuse.
Indomethacin inhibits melanogenesis via down-regulation of Mitf mRNA transcription
Authors: Sato Kazuomi , Takei Masahiro , Iyota Ray , Muraoka Yoshimasa , Nagashima Marika , Yoshimura Yoshitaka
Published: November 2017

Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit several divergent biological effects. In this study, we investigated the effect of indomethacin on melanin synthesis using B16F1 melanoma cells. Indomethacin inhibited α-melanocyte stimulating hormone (α-MSH)-enhanced melanin synthesis in a dose-dependent manner. Western blotting analysis revealed that indomethacin significantly suppressed tyrosinase and Mitf protein levels. In a luciferase reporter assay, we found that indomethacin reduced tyrosinase promoter activity. Moreover, real-time RT-PCR analysis showed that indomethacin lowered mRNA levels of melanogenic genes, including Mitf. Together, our findings indicate that indomethacin inhibits melanogenesis via the suppression of Mitf transcription.
Heterologous expression of two minor laccase isozyme cDNAs from the edible mushroom Grifola frondosa
Authors: Nitheranont Thitinard , Watanabe Akira , Asada Yasuhiko
Published: November 2017

Two cDNAs encoding the minor laccase isozymes (Lac2 and Lac3) of Grifola frondosa were cloned, characterized, and expressed in Pichia pastoris. The recombinant Lac2 (rLac2) was stable at pH 6.0, whereas the recombinant Lac3 (rLac3) was stable in a broad pH range (pH 4.0–8.0). In addition, rLac2 and rLac3 showed the highest catalytic efficiency (kcat/Km) for 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid).
Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology
Authors: Sluijter Joost Petrus Gerardus , Davidson Sean Michael , Boulanger Chantal M , Buzás Edit Iren , de Kleijn Dominique Paschalis Victor , Engel Felix Benedikt , Giricz Zoltán , Hausenloy Derek J , Kishore Raj , Lecour Sandrine , Leor Jonathan , Madonna Rosalinda , Perrino Cinzia , Prunier Fabrice , Sahoo Susmita , Schiffelers Ray Michel , Schulz Rainer , Van Laake Linda Wilhelmina , Ytrehus Kirsti , Ferdinandy Péter
Published: November 2017

Extracellular vesicles (EVs)—particularly exosomes and microvesicles (MVs)—are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized. These capabilities include transporting regulatory molecules including different RNA species, lipids, and proteins through the extracellular space including blood and delivering these cargos to recipient cells to modify cellular activity. EVs powerfully stimulate angiogenesis, and can protect the heart against myocardial infarction. They also appear to mediate some of the paracrine effects of cells, and have therefore been proposed as a potential alternative to cell-based regenerative therapies. Moreover, EVs of different sources may be useful biomarkers of cardiovascular disease identities. However, the methods used for the detection and isolation of EVs have several limitations and vary widely between studies, leading to uncertainties regarding the exact population of EVs studied and how to interpret the data. The number of publications in the exosome and MV field has been increasing exponentially in recent years and, therefore, in this ESC Working Group Position Paper, the overall objective is to provide a set of recommendations for the analysis and translational application of EVs focussing on the diagnosis and therapy of the ischaemic heart. This should help to ensure that the data from emerging studies are robust and repeatable, and optimize the pathway towards the diagnostic and therapeutic use of EVs in clinical studies for patient benefit.
Medical School Applicant Characteristics Associated With Performance in Multiple Mini-Interviews Versus Traditional Interviews: A Multi-Institutional Study
Authors: Henderson Mark C. , Kelly Carolyn J. , Griffin Erin , Hall Theodore R. , Jerant Anthony , Peterson Ellena M. , Rainwater Julie A. , Sousa Francis J. , Wofsy David , Franks Peter
Published: November 2017

Purpose

To examine applicant characteristics associated with multiple mini-interview (MMI) or traditional interview (TI) performance at five California medical schools.

Method

Of the five California Longitudinal Evaluation of Admission Practices consortium schools, three used TIs and two used MMIs. Schools provided retrospective data on 2011–2013 admissions cycle interviewees: age, gender, race/ethnicity (underrepresented in medicine [UIM] or not), disadvantaged (DA) status, undergraduate GPA, Medical College Admission Test (MCAT) score, and interview score (standardized as z score; mean = 0; SD = 1). Adjusted linear regression analyses, stratified by interview type, examined associations with interview performance.

Results

The 4,993 applicants who completed 7,516 interviews included 931 (18.6%) UIM and 962 (19.3%) DA individuals; 3,226 (64.6%) had only 1 interview. Mean age was 24.4 (SD = 2.7); mean GPA and MCAT score were 3.72 (SD = 0.22) and 33.6 (SD = 3.7), respectively. Older age, female gender, and number of prior interviews were associated with better performance on both MMIs and TIs. Higher GPA was associated with lower MMI scores (z score, per unit GPA = −0.26; 95% CI = −0.45, −0.06) but unrelated to TI scores. DA applicants had higher TI scores (z score = 0.17; 95% CI = 0.07, 0.28) but lower MMI scores (z score = −0.18; 95% CI = −0.28, −0.08) than non-DA applicants. Neither UIM status nor MCAT score was associated with interview performance.

Conclusions

These findings have potentially important workforce implications, particularly regarding MMI performance of DA applicants, and illustrate the need for other multi-institutional studies.
Hearing Handicap and Speech Recognition Correlate With Self-Reported Listening Effort and Fatigue
Authors: Alhanbali Sara , Dawes Piers , Lloyd Simon , Munro Kevin J
Published: November 2017

Objectives:

To investigate the correlations between hearing handicap, speech recognition, listening effort, and fatigue.

Design:

Eighty-four adults with hearing loss (65 to 85 years) completed three self-report questionnaires: the Fatigue Assessment Scale, the Effort Assessment Scale, and the Hearing Handicap Inventory for Elderly. Audiometric assessment included pure-tone audiometry and speech recognition in noise.

Results:

There was a significant positive correlation between handicap and fatigue (r = 0.39, p < 0.05) and handicap and effort (r = 0.73, p < 0.05). There were significant (but lower) correlations between speech recognition and fatigue (r = 0.22, p < 0.05) or effort (r = 0.32, p< 0.05). There was no significant correlation between hearing level and fatigue or effort.

Conclusions:

Hearing handicap and speech recognition both correlate with self-reported listening effort and fatigue, which is consistent with a model of listening effort and fatigue where perceived difficulty is related to sustained effort and fatigue for unrewarding tasks over which the listener has low control. A clinical implication is that encouraging clients to recognize and focus on the pleasure and positive experiences of listening may result in greater satisfaction and benefit from hearing aid use.
Genetic Variant of PAX1 Gene Is Functionally Associated With Adolescent Idiopathic Scoliosis in the Chinese Population
Authors: Xu Leilei , Sheng Fei , Xia Chao , Qin Xiaodong , Tang Nelson Leung-Sang , Qiu Yong , Cheng Jack Chun-Yiu , Zhu Zezhang
Published: November 2017

Study Design.

A genetic association study.

Objective.

To investigate the association between PAX1 gene and the susceptibility of adolescent idiopathic scoliosis (AIS) in the Chinese population and to further determine the functional variant regulating PAX1 expression in patients with AIS.

Summary of Background Data.

In a previous study an enhancer locus of PAX1 was reported to be associated with the development of AIS in the Caucasian and the Japanese population. However, there is a paucity of knowledge concerning the functional role of PAX1 in the Chinese AIS population.

Methods.

The single-nucleotide polymorphisms rs6137473 and rs169311 were genotyped in 2914 patients and 3924 controls. The differences of genotype and allele distributions between patients and controls were calculated using chi-square test. Paraspinal muscles were collected from 84 patients with AIS. The one-way analysis of variance test was used to compare the mRNA expression of PAX1 among different genotypes.

Results.

Both rs6137473 and rs169311 were significantly associated with the susceptibility of AIS. Allele G of rs6137473 and allele A of rs169311 can significantly add to the risk of AIS with an odds ratio of 1.17 and 1.22, respectively. Moreover, there was significant difference regarding the expression of the PAX1 between the concave side and convex side of the patients. Patients with genotype AA of rs169311 had significantly decreased expression of PAX1 than those with genotype CC. As for rs6137473, no remarkable difference of PAX1 expression was found among the three genotypes.

Conclusion.

The association between PAX1 and the susceptibility of AIS was successfully replicated in the Chinese population. Moreover, rs169311 could be a functional variant regulating the expression of PAX1 in the paraspinal muscles of AIS. Further functional analysis is warranted for a comprehensive knowledge on the contribution of this variant to the development of AIS.

Level of Evidence: 3
Licensed Vocational Nurse Residency Program in Primary Care
Authors: Dannemeyer Deborah , Jalandoni Cecile , Vonderheide Dawn
Published: November 2017

This article will explain one organization’s experience in developing a licensed vocational nurse residency program in an ambulatory setting, the barriers and challenges, and program outcomes. It outlines results of the program in building competence and confidence for vocational nurses to perform as effective team members in the primary care office setting. Learnings from this experience may be applied to enhance new and transitioning employee orientation and education programs in ambulatory and inpatient settings.
The Differential Diagnosis of Vertigo in Children
Authors: Davitt Meghan , Delvecchio Michael T. , Aronoff Stephen C.
Published: November 2017

Objectives

Vertigo is a relatively common complaint in children with 5.3% of pediatric patients complaining of this symptom. Although the causes of vertigo have been well established in adults, the diagnoses in children have not been well described. The aims of this systematic review are to discover the current information regarding etiologies of vertigo in children and to determine the most common diagnoses that present with vertigo in pediatric patients.

Methods

PubMed, Scopus, and Embase were searched using the PRISMA guidelines. The inclusion and exclusion criteria were established a priori. All results were analyzed using a Bayesian methodology for point estimation and credible interval calculation.

Results

From the database searches, 1419 titles were reviewed. Twenty-two studies met inclusion criteria. From these studies, a total of 2726 children aged 2 months to 19 years were reported. The top 4 diagnoses associated with childhood vertigo include vestibular migraine (23.8%; credible interval, 22.3%–25.5%), benign paroxysmal vertigo of childhood (13.7%; credible interval, 12.4%–15%), idiopathic or no identified association (11.7%; credible interval, 10.5%–12.9%), and labyrinthitis/vestibular neuronitis (8.47%, credible interval, 7.46%–9.55%) accounting for approximately 57% of cases. Less common diagnoses included Meniere disease and central nervous system tumors.

Conclusions

Although the most common causes of pediatric vertigo include vestibular migraine and benign paroxysmal vertigo of childhood, the etiologies are myriad. Rates and credible intervals are provided to permit a probabilistic diagnostic approach to these children.
Point-of-Care Ultrasound Identification of Internal Jugular Vein Thrombosis in Newly Diagnosed Lymphoma
Authors: Ekstrom Joanna C. , Whitcomb Valerie , Bergmann Kelly R.
Published: November 2017

We present a case of a child who presented with neck swelling and was ultimately diagnosed with lymphoma after an internal jugular vein thrombosis was discovered by point-of-care ultrasound. The use of point-of-care ultrasound enabled thrombus detection, which prompted further evaluation and treatment.
Automated External Defibrillators in High Schools
Authors: Thornton Matthew D. , Cicero Mark X. , McCabe Megan E. , Chen Lei
Published: November 2017

Objectives

Automated external defibrillators (AEDs) have demonstrated increased survival in out-of-hospital cardiac arrest, and their prevalence continues to rise. In 2009, Connecticut passed a legislation requiring all schools to have an AED, barring financial barriers. The objectives of this study were (1) to determine if this legislation was associated with an increase in Connecticut high school AEDs and (2) to detect disparities in the availability of AEDs based on school type, student demographics, and school size.

Study Design

A single researcher conducted a scripted telephone survey of all 54 public and 13 private high schools in New Haven County, Connecticut.

Results

A response rate of 100% was achieved. Forty-nine percent of high schools had an AED before the legislation, compared with 88% after (P < 0.001). Before legislation, private schools had a higher percentage of AEDs than public schools (69% vs 44%; P = 0.1). Postlegislation, the difference is less (92% vs 87%; P = 0.4). Small schools (<400 students) are significantly less likely to have an AED than larger schools (40% vs 100%; P < 0.001). Schools with a higher percentage of students with disabilities are also less likely to have an AED (P = 0.005), even when controlling for school size (P = 0.03).

Conclusions

State legislation requiring schools to have an AED, if financially feasible, was associated with a significant increase in AED presence among New Haven County high schools. Small high schools and those with a higher percentage of students with disabilities remain less likely to have an AED despite legislation.
Recognition and Management of Pediatric Salt Toxicity
Authors: Blohm Eike , Goldberg Amy , Salerno Ann , Jenny Carole , Boyer Edward , Babu Kavita
Published: November 2017

Objectives

Immediate recognition of salt toxicity and aggressive resuscitative measures are critical in the treatment of this lethal poisoning. Despite heroic measures, pediatric deaths due to salt toxicity still occur from irreversible neurological damage. The objective of this article is to review the relevant literature and offer a therapeutic algorithm for the management of pediatric patients presenting with salt toxicity.

Methods

A literature search for cases of salt toxicity was conducted. Articles in English that were available electronically through PubMed and Google Scholar were reviewed.

Results

Nineteen cases and case series of salt toxicity were located using our search strategy. Salt poisoning has a distinct pathophysiology compared with hypernatremia, most notable for the lack of formation of idiogenic osmoles.

Conclusions

The approach to treatment differs between salt toxicity and hypernatremia, focusing on rapid correction of serum osmolality rather than gradual normalization of serum sodium concentrations. Consultation of nephrology and child protection services are strongly recommended in the comprehensive treatment approach.
Ventricular Tachycardia Induced by Propafenone Intoxication in a Pediatric Patient
Authors: Rosa Margherita , Pappacoda Serena , D'Anna Carolina , Di Mita Onorina , Ponticiello Eduardo , Marzuillo Pierluigi , Tipo Vincenzo
Published: November 2017

Unintentional poisonings are a global health problem frequently resulting in hospital admissions. Propafenone is a class 1C antiarrhythmic drug used in the second-line management of supraventricular and ventricular arrhythmias and, when unintentionally ingested, can lead to severe and life-threatening poisoning. We describe a case of a 3-year-old male patient unintentionally ingesting 300 mg (20 mg/kg) of propafenone and presenting with ventricular tachycardia with QT prolongation. Two boli of intravenous hypertonic sodium bicarbonate (total amount of 3 mEq/kg), followed by 3-hours continuous infusion of 1 mEq kg−1 h−1 sodium bicarbonate, were able to restore the clinical conditions of the patient. With this case report, we aim to highlight the existing challenge in the therapeutic management of propafenone intoxication that finds intravenous hypertonic bicarbonate to be a useful tool also in pediatric population.
Spanish Language Pelvic Floor Disorders Patient Information Handouts: How Readable Are They?
Authors: Robb James , Mackay Alex , Rondeau Nancy , Palomino Javier , Mulla Zuber D. , Montoya T. Ignacio , Mallett Veronica T.
Published: November 2017

Objective

This study aimed to determine the readability of commonly available patient information materials for pelvic floor disorders written in Spanish and compare their readability based on type of content and source.

Methods

Spanish patient information handouts, including pamphlets from the National Institutes of Health, International Urogynecology Association, American Congress of Obstetricians and Gynecologists, online printable handouts, and industry-sponsored brochures were assessed for readability. Online materials for patients were obtained from Google searches using key words (pelvic floor disorders, urogynecology, patient information handouts, Spanish). Reading difficulty was assessed using INFLESZ v1.0, (Barrio-Cantalejo IM, Spain) a free software developed to calculate the readability of Spanish written texts. Three index scales were used: Flesch-Szigriszt Index, Word correlation Index, and the Fernandez-Huerta Index.

Results

Forty patient information handouts were analyzed. All pamphlets analyzed had readability scores within the “average” to “very difficult” reading difficulty levels as per the index scales used. None of the analyzed pamphlets met the sixth grade reading level criteria suggested by the National Institutes of Health and American Medical Association, including government-developed materials. There were no differences in readability scores between type of leaflet content or source.

Conclusions

Current available free, industry-, organization-, and government-provided reading materials in Spanish do not serve the Spanish-speaking only or low English-speaking literacy population. Future work should aim to simplify the language in such documents to the suggested sixth grade reading level.
Environmental influences and ontogenetic differences in vertical habitat use of black marlin (
Istiompax indica
) in the southwestern Pacific
Authors: Williams Samuel M. , Holmes Bonnie J. , Tracey Sean R. , Pepperell Julian G. , Domeier Michael L. , Bennett Michael B.
Published: November 2017

The black marlin (
Istiompax indica
) is a highly migratory billfish that occupies waters throughout the tropical and subtropical Indo-Pacific. To characterize the vertical habitat use of
I. indica
, we examined the temperature-depth profiles collected using 102 pop-up satellite archival tags deployed off the east coast of Australia. Modelling of environmental variables revealed location, sea-surface height deviation, mixed layer depth and dissolved oxygen to all be significant predictors of vertical habitat use. Distinct differences in diel movements were observed between the size classes, with larger size classes of marlin (greater than 50 kg) undertaking predictable bounce-diving activity during daylight hours, while diving behaviour of the smallest size class occurred randomly during both day and night. Overall, larger size classes of
I. indica
were found to use an increased thermal range and spend more time in waters below 150 m than fish of smaller size classes. The differences in the diving behaviour among size classes were suggested to reflect ontogenetic differences in foraging behaviour or physiology. The findings of this study demonstrate, for the first time to our knowledge, ontogenetic differences in vertical habitat in a species of billfish, and further the understanding of pelagic fish ecophysiology in the presence of global environmental change.
Laryngeal airway reconstruction indicates that rodent ultrasonic vocalizations are produced by an edge-tone mechanism
Authors: Riede Tobias , Borgard Heather L. , Pasch Bret
Published: November 2017

Some rodents produce ultrasonic vocalizations (USVs) for social communication using an aerodynamic whistle, a unique vocal production mechanism not found in other animals. The functional anatomy and evolution of this sound production mechanism remains unclear. Using laryngeal airway reconstruction, we identified anatomical specializations critical for USV production. A robust laryngeal cartilaginous framework supports a narrow supraglottal airway. An intralaryngeal airsac-like cavity termed the ventral pouch was present in three muroid rodents (suborder Myomorpha), but was absent in a heteromyid rodent (suborder Castorimorpha) that produces a limited vocal repertoire and no documented USVs. Small lesions to the ventral pouch in laboratory rats caused dramatic changes in USV production, supporting the hypothesis that an interaction between a glottal exit jet and the alar edge generates ultrasonic signals in rodents. The resulting undulating airflow around the alar edge interacts with the resonance of the ventral pouch, which may function as a Helmholtz resonator. The proposed edge-tone mechanism requires control of intrinsic laryngeal muscles and sets the foundation for acoustic variation and diversification among rodents. Our work highlights the importance of anatomical innovations in the evolution of animal sound production mechanisms.
WorMachine: Machine Learning-Based Phenotypic Analysis Tool for Worms
Authors: Hakim Adam , Mor Yael , Toker Itai Antoine , Levine Amir , Markovitz Yishai , Rechavi Oded
Published: November 2017

WhileCaenorhabditis elegansnematodes are powerful model organisms, quantification of visible phenotypes is still often labor-intensive, biased, and error-prone. We developed “WorMachine”, a three-step MATLAB-based image analysis software that allows automated identification ofC. elegansworms, extraction of morphological features, and quantification of fluorescent signals. The program offers machine learning techniques which should aid in studying a large variety of research questions. We demonstrate the power of WorMachine using five separate assays: scoring binary and continuous sexual phenotypes, quantifying the effects of different RNAi treatments, and measuring intercellular protein aggregation. Thus, WorMachine is a “quick and easy”, high-throughput, automated, and unbiased analysis tool for measuring phenotypes.
Neural systems of cognitive demand avoidance
Authors: Sayalı Ceyda , Badre David
Published: November 2017

Cognitive effort is typically aversive, evident in people’s tendency to avoid cognitively demanding tasks. The ‘cost of control’ hypothesis suggests that engagement of cognitive control systems of the brain makes a task costly and the currency of that cost is a reduction in anticipated rewards. However, prior studies have relied on binary hard versus easy task subtractions to manipulate cognitive effort and so have not tested this hypothesis in “dose-response” fashion. In a sample of 50 participants, we parametrically manipulated the level of effort during fMRI scanning by systematically increasing cognitive control demands during a demand-selection paradigm over six levels. As expected, frontoparietal control network (FPN) activity increased, and reward network activity decreased, as control demands increased across tasks. However, avoidance behavior was not attributable to the change in FPN activity, lending only partial support to the cost of control hypothesis. By contrast, we unexpectedly observed that the deactivation of a task-negative brain network corresponding to the Default Mode Network (DMN) across levels of the cognitive control manipulation predicted the change in avoidance. In summary, we find partial support for the cost of control hypothesis, while highlighting the role of task-negative brain networks in modulating effort avoidance behavior.
HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2
Authors: Cao Ji , Sun Lei , Aramsangtienchai Pornpun , Spiegelman Nicole A. , Zhang Xiaoyu , Seto Edward , Lin Hening
Published: November 2017

The smallest histone deacetylase (HDAC) and the only class IV HDAC member, HDAC11, is reported to regulate immune activation and tumorigenesis, yet its physiological function is largely unknown. Here we identify HDAC11 as an efficient lysine defatty-acylase that is >10,000-fold more efficient than its deacetylase activity. Through proteomics studies, we identified SHMT2 as a defatty-acylation substrate of HDAC11. HDAC11-catalyzed defatty-acylation did not affect the enzymatic activity of SHMT2. Instead, it affects the ability of SHMT2 to regulate type I interferon receptor ubiquitination and internalization. Correspondingly, HDAC11 depletion increased type I interferon signaling in both cell culture and mice. This study is the first time a zinc-dependent HDAC is found to have an activity that is much more efficient than the corresponding deacetylase activity. The finding expands the physiological functions of HDAC11 and protein lysine fatty acylation, and opens up opportunities to develop HDAC11-specific inhibitors as therapeutics to modulate immune responses.
Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model
Authors: Bajanca Fernanda , Vandel Laurence
Published: November 2017

Histone acetyl transferases (HATs) and histone deacetylases (HDAC) control transcription during myogenesis. HDACs promote chromatin condensation, inhibiting gene transcription in muscle progenitor cells until myoblast differentiation is triggered and HDACs are released. HATs, namely CBP/p300, activate myogenic regulatory and elongation factors promoting myogenesis. HDAC inhibitors are known to improve regeneration in dystrophic muscles through follistatin upregulation. However, the potential of directly modulating HATs remains unexplored. We tested this possibility in a well-known zebrafish model of Duchenne muscular dystrophy. Interestingly, CBP/p300 transcripts were found downregulated in the absence of Dystrophin. While investigating CBP rescuing potential we observed that dystrophin-null embryos overexpressing CBP actually never show significant muscle damage, even before a first regeneration cycle could occur. We found that the pan-HDAC inhibitor trichostatin A (TSA) also prevents early muscle damage, however the single HAT CBP is as efficient even in low doses. The HAT domain of CBP is required for its full rescuing ability. Importantly, both CBP and TSA prevent early muscle damage without restoring endogenous CBP/p300 neither increasing follistatin transcripts. This suggests a new mechanism of action of epigenetic regulators protecting dystrophin-null muscle fibres from detaching, independent from the known improvement of regeneration upon damage of HDACs inhibitors. This study builds supporting evidence that epigenetic modulators may play a role in determining the severity of muscle dystrophy, controlling the ability to resist muscle damage. Determining the mode of action leading to muscle protection can potentially lead to new treatment options for muscular dystrophies in the future.
Exploiting delayed transitions to sustain semiarid ecosystems after catastrophic shifts
Authors: Vidiella, Blai , Sardanyés Josep , Solé Ricard V.
Published: November 2017

Semiarid ecosystems (including arid, semiarid and dry-subhumid ecosystems) span more than 40% of extant habitats and a similar percentage of human population. As a consequence of global warming, these habitats face future potential shifts towards the desert state characterized by an accelerated loss of diversity and stability leading to collapse. Such possibility has been raised by several mathematical and computational models, along with several early warning signal methods applied to spatial vegetation patterns. Here we show that just after a catastrophic shift has taken place an expected feature is the presence of a ghost, i.e., a delayed extinction associated to the underlying dynamical flows. As a consequence, a system might exhibit for very long times an apparent stationarity hiding in fact an inevitable collapse. Here we explore this problem showing that the ecological ghost is a generic feature of standard models of green-desert transitions including facilitation. If present, the ghost could hide warning signals, since statistical patterns are not be expected to display growing fluctuations over time. We propose and computationally test a novel intervention method based on the restoration of small fractions of desert areas with vegetation as a way to maintain the fragile ecosystem beyond the catastrophic shift caused by a saddle-node bifurcation, taking advantage of the delaying capacity of the ghost just after the bifurcation.
Radioactive Labeling and Fractionation of Fission Yeast Walls
Authors: Pérez Pilar , Ribas Juan C.
Published: November 2017

Fungal cells contain an essential structure external to the cell, made of polysaccharides and proteins, termed the cell wall. Polysaccharides represent ∼96% of the cell wall on a dry-weight basis. They are complex insoluble polymers connected to each other by covalent linkages and hydrogen bonds with specific localizations in the cell wall and septum. Fission yeast contains three β-glucans (a major branched β(1,3)-glucan, a minor linear β(1,3)-glucan, and a minor branched β(1,6)-glucan), two α-glucans (a major α(1,3)-glucan and a minor α(1,4)-glucan), and a minor amount of galactomannan-linked glycoproteins. We provide here a simple protocol to label uniformly the cell wall using d-[U-14C]-glucose as a carbon source and to fractionate the cell wall into the three or four main cell wall components: galactomannoproteins, α-glucan, and β-glucan, which can be subdivided into β(1,3)-glucan and β(1,6)-glucan. This simple protocol uses enzymatic and chemical fractionations of the different cell wall components that permit the quantification of each polysaccharide in the cell wall and in the cell. This protocol is very useful for the analysis of the many morphological alterations caused by a variety of cellular processes that ultimately affect the cell wall and thus cell morphogenesis.
Preparation of Single-Stranded Bacteriophage M13 DNA by Precipitation with Polyethylene Glycol
Authors: Green Michael R. , Sambrook Joseph
Published: November 2017

Bacteriophage M13 single-stranded DNA is prepared from virus particles secreted by infected bacteria into the surrounding medium. Several methods are available to purify the polymorphic filamentous particles. In this protocol, the particles are concentrated by precipitation with polyethylene glycol (PEG) in the presence of high salt. Subsequent extraction with phenol releases the single-stranded DNA, which is then collected by precipitation with ethanol. The resulting preparation is pure enough to be used as a template for DNA sequencing. A yield of 5–10 µg of single-stranded DNA/mL of infected cells may be expected from recombinant bacteriophages bearing inserts of 300–1000 nt.
In Vivo Transfection of Naked DNA into Xenopus Tadpole Tail Muscle
Authors: Marshall Lindsey , Girardot Fabrice , Demeneix Barbara A. , Coen Laurent
Published: November 2017

In vivo gene transfer systems are important to study foreign gene expression and promoter regulation in an organism, with the benefit of exploring this in an integrated environment. Direct injection of plasmids encoding exogenous promoters and genes into muscle has numerous advantages: the protocol is easy, efficient, and shows time-persistent plasmid expression in transfected muscular cells. After injecting naked-DNA plasmids into tadpole tail muscle, transgene expression is strong, reproducible, and correlates with the amount of DNA injected. Moreover, expression is stable as long as the tadpoles remain, or are maintained, in premetamorphic stages. By directly expressing genes and regulated promoters in Xenopus tadpole muscle in vivo, one can exploit the powerful experimental advantages of gene transfer systems in an intact, physiologically normal animal.
Implications of failure to achieve a result from prenatal maternal serum cell‐free DNA testing: a historical cohort study
Authors: Chan N , Smet M‐E , Sandow R , da Silva Costa F , McLennan A
Published: November 2017

Objective

To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non‐invasive prenatal testing (NIPT).

Design

Historical cohort study.

Setting

A multicentre private practice in Sydney, Australia.

Population

Women who failed to obtain a result from NIPT (n = 131).

Methods

The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population.

Main outcome measures

Antenatal investigations: pregnancy‐associated plasma protein‐A (PAPP‐A), free β‐human chorionic gonadotrophin (β‐hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre‐eclampsia, gestational diabetes, small‐for‐gestational‐age (SGA), preterm delivery.

Results

Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre‐eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP‐A MoM (0.75 versus 1.14, P < 0.0001), decreased free β‐hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02).

Conclusion

Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre‐eclampsia.

Funding

None received.

Tweetable abstract

Women who fail to obtain a result from cell‐free DNA NIPT are at increased risk of adverse pregnancy outcomes.
Human cadavers preserved using Thiel's method for the teaching of fibreoptically‐guided intubation of the trachea: a laboratory investigation
Authors: László C. J. , Szűcs Z. , Nemeskéri Á. , Baksa G. , Szuák A. , Varga M. , Tassonyi E.
Published: November 2017

We assessed the suitability of human cadavers preserved using Thiel's method for teaching flexible fibreoptic tracheal intubation. Thirty‐one anaesthetists unacquainted with this technique received didactic teaching followed by handling of the fibrescope on the Oxford teaching box. They then carried out fibreoptic intubations in two cadavers to establish a baseline sample of their intubation skills. Thereafter, we randomly assigned the trainees to two groups to practice fibreoptic intubation either on two distinct cadavers or on two airway manikins. After 7 days we re‐assessed procedural skills using the same cadavers as at baseline. Intubation time was the primary outcome and secondary outcomes included the incidence of failed intubations. We also evaluated trainee satisfaction. The mean (SD) intubation time decreased from a baseline value of 74 (20) s to 35 (6) s in the cadaver group and to 56 (16) s in the manikin group. The effect of ‘time’ was significant (p = 0.002), indicating that both methods of training led to improvements. The training effect of the cadaveric method was greater than with the manikin method (p = 0.0016). Thirty‐four failed intubations occurred at baseline vs. eight at the end of study (RR 0.24, 95%CI 0.11–0.51, p = 0.0002, NNT 9.6); six in the cadaver group and two in the manikin group (p = 0.22). We conclude that human cadavers preserved using Thiel's method are potentially better for teaching flexible fibreoptic tracheal intubation compared with manikins.
Thickness mapping of individual retinal layers and sectors by Spectralis SD‐OCT in Autosomal Dominant Optic Atrophy
Authors: Corajevic Nihada , Larsen Michael , Rönnbäck Cecilia
Published: November 2017

Purpose

To assess layer‐ and location‐specific retinal thickness deficits in autosomal dominant optic atrophy (ADOA) using Spectralis SD‐OCT.

Methods

This cross‐sectional study included 41 ADOA patients with OPA1 exon 28 (2826delT) mutation [age, 8.6–83.5 years; best‐corrected visual acuity (BCVA), 8–89 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] and 55 mutation‐free first‐degree relatives as healthy controls (age, 8.9–68.7; BCVA, 80–99).

Participants underwent routine examination and optical coherence tomography (OCT) with segmentation of the whole retina, inner retinal layers (IRL) and outer retinal layers (ORL). Individual segmentation was performed of the perifoveal retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE) and the peripapillary RNFL. Combinations of layers and sectors were tested for their diagnostic significance. Only right eye data are presented. Statistical analysis was adjusted for age, gender, spherical equivalent, axial length and family clustering in a mixed model analysis.

Results

The perifoveal RNFL, GCL, IPL and the peripapillary RNFL were all significantly thinner in ADOA patients than in healthy controls (p < 0.0001). No statistical difference was found for other layers. The most prominent and diagnostically most valuable deficit was found in the GCL (−49.9%) in the ‘nasal inner macula’ (NIM) sector (−63%). Attenuation of the peripapillary RNFL was most significant in the temporal sector (−58.4%).

Conclusion

In ADOA, retinal ganglion cells are most prominently reduced in the nasal perifoveal area of the GCL, which together with the temporal peripapillary RNFL area serves as the strongest diagnostic OCT marker.
The empirical effects of competition on third‐degree price discrimination in the presence of arbitrage
Authors: Boik Andre
Published: November 2017

Since Borenstein and Holmes, a theoretical and empirical literature has emerged that examines the effects of competition on third‐degree price discrimination. Since transaction costs involved in conducting arbitrage are typically unobserved, empirical investigations in this area have largely been restricted to markets such as for air travel where arbitrage is difficult, if not impossible. Using an entirely novel dataset, this paper documents the effect of competition on price discrimination in the presence of arbitrage in the Canadian online sports betting market where prices for Canadian teams are higher than in the world market. I observe how the prices of Canadian teams change in real time in response to the presence of arbitrageurs that establish Canadian sportsbooks’ observable marginal opportunity costs. I exploit the existence of government betting outlets not subject to arbitrage to obtain reduced form counterfactual estimates of the extent to which competition affects price discrimination in the presence of arbitrage. In this new empirical environment, I find results consistent with the airline literature: competition reduces overall price dispersion and markups, but dispersion and markups shrink more for those in the “strong” market than the “weak” market.
Exporting and labour demand: Micro‐level evidence from Germany
Authors: Lichter Andreas , Peichl Andreas , Siegloch Sebastian
Published: November 2017

It is widely believed that globalization increases the extent of employment and wage responses to economic shocks. In this paper, we investigate the effect of firms’ exporting activities on the wage elasticity of labour demand. Using rich, administrative linked employer–employee panel data from Germany and destination‐specific industry‐level information on trade flows, we explicitly control for self‐selection into exporting and endogeneity concerns. Overall, we find that exporting has a significant positive effect on the (absolute value of the) unconditional wage elasticity of labour demand. In line with our hypothesis, we further show that the effect is particularly strong for those plants that export a significant share of their output to low‐ and medium‐income countries, hence face relatively more price‐elastic product demand.
FINANCIAL MARKETS' SHUTDOWN AND REACCESS
Authors: Agnello Luca , Castro Vítor , Sousa Ricardo M.
Published: November 2017

We employ a discrete‐time parametric duration model on a group of 121 countries over the period 1970–2011 and find that the probability of the end of financial markets' shutdown and reaccess falls as these events become longer. We also show that: (1) shutdown episodes are longer when economic prospects are poor and the degree of financial openness falls, the chief executive has been in office for long periods, and the country has a default history and (2) spells of reaccess tend to be longer when economic growth improves and financial openness increases, there are neither government crises nor government instability, and the country did not default in the past. (JEL C41, G15)