bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Indoor and Outdoor Radon Equilibrium Factors—part I: 222Rn
Authors: Chen Jing , Harley Naomi H.
Published: August 2018

Radon exposure limits are given in terms of radon gas concentration in the air. However, in the calculation of radon dose to the lung, the radon equilibrium equivalent concentration is used. The measured equilibrium factor times the measured radon gas concentration estimates the equilibrium equivalent concentration. Therefore, the equilibrium factor is an important factor in radon dose calculations. A review of published measurements of equilibrium factors shows a range of values reported in studies from more than 20 countries, measured in indoor residential, indoor public, and outdoor environments. Values for 222Rn are reported and discussed here, with special attention paid to results from India and China, where measured equilibrium factors are reported for hundreds and thousands of households, respectively. The wide range of equilibrium factors suggests that location-specific values are more appropriate than a worldwide average value in the calculation of lung bronchial dose.
Lessons Learned From a Quad-State Postdisaster Project
Authors: Hansel Tonya , Osofsky Howard , Langhinrichsen-Rohling Jennifer , Osofsky Joy , Rehner Timothy , Wornell Cory , Speier Anthony , Brazeal Michelle , Arthur Elizabeth , Rohrer Glenn
Published: August 2018

The Mental and Behavioral Health (MBH) Capacity Project had a mission shared among 4 states to support MBH sustainability along the Gulf Coast. Integration of mental health into undersourced primary health clinics was an important goal of the project. The findings from the collaborative evaluation demonstrate long-term outcomes including the following: community has greater capacity and sustainability for quality health care; better informed and connected communities; and individuals are more informed, connected, and resilient. Lessons learned indicate that improved population health outcomes are possible even in low-income, high-stress regions through intentional and collaborative efforts integrating MBH into primary cares settings.
The Effect of Body Mass Index on Rehabilitation of Patients with Amputation
Authors: Burke David T. , Al-Adawi Samir , Jain Nitin B. , Burke Daniel P.
Published: August 2018

Introduction

This retrospective cohort study was designed to investigate the association between body mass index (BMI) and the functional progress of 327 consecutive patients with amputation admitted to the amputee unit of a freestanding acute care rehabilitation hospital between January 2000 and April 2006.

Methods

Data were analyzed during the period of January 2000 to April 2006 from all previously amputated patients admitted and discharged from an acute freestanding rehabilitation hospital. Data were retrieved from the medical record including diagnosis, height, and weight measured before amputation, functional independence measurements (FIMs) scored on admission and discharge, and the length of rehabilitation hospitalization.

Results

After adjusting for age, sex, and length of stay, the FIM gain per day was the highest among those in the obese class I, followed by those in obese class III and the underweight group.

Conclusions

In patients undergoing rehabilitation after amputation, FIM gain per day is not significantly associated with BMI. Thus, obese patients can expect to have functional gains that are similar to patients with normal BMI after amputation.
Relationships of Microbiome Markers With Extraintestinal, Psychological Distress and Gastrointestinal Symptoms, and Quality of Life in Women With Irritable Bowel Syndrome
Authors: Hollister Emily B. , Cain Kevin C. , Shulman Robert J. , Jarrett Monica E. , Burr Robert L. , Ko Cynthia , Zia Jasmine , Han Claire J. , Heitkemper Margaret M.
Published: August 2018

Introduction:

Altered microbial diversity has been associated with gastrointestinal (GI) symptoms in persons with irritable bowel syndrome (IBS). Less is known about the relationship of microbiome with extraintestinal pain and psychological distress symptoms and quality of life (QOL) in persons with IBS. We aimed to evaluate the relationship of fecal microbiota to GI symptoms, stool consistency, psychological distress, extraintestinal pain, and QOL in participants meeting Rome III criteria for IBS.

Methods:

Seventy-six women completed a 28-day diary that included GI, stool consistency, psychological distress, and extraintestinal pain ratings. Participants completed the IBS-Specific Quality of Life questionnaire. Stool samples were collected and analyzed by 16S rRNA gene sequencing. Principal component analysis was performed and the first 2 components (PC1, PC2) were used to test relationships among bacterial families and clinical measures.

Results:

Participants were categorized as IBS constipation (n=22), IBS diarrhea (n=39), IBS mixed (n=13), and IBS unsubtyped (n=2). There was a significant group effect for the Firmicutes to Bacteroidetes ratio and PC1. Lower microbial diversity and richness were associated with increased urgency and extraintestinal pain, worse QOL, and looser stools. Lower extraintestinal pain was associated with increased Rikenellaceae, Christensenellaceae, Dehalobabacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae, Sutterellaceae, Desulfovibrionaceae, and Erysipelotrichaceae abundances. QOL was positively associated with many of these same bacterial families. Higher Firmicutes to Bacteroidetes ratio was positively associated with loose stools. There were no statistically significant relationships between daily psychological distress or abdominal pain and bacterial families.

Conclusions:

Stool microbial diversity and composition are linked to daily extraintestinal symptoms, stool consistency, and QOL in women with IBS.
Peripartum Maternal Hepatitis B Care in a US Nationwide Data Set
Authors: Chang Matthew S. , Wharam J. Frank , Zhang Fang , LeCates Robert F. , Morton-Eggleston Emma , Tuomala Ruth E. , Rutherford Anna E. , Mutinga Muthoka L. , Andersson Karin L. , Brown Robert S. , Ukomadu Chinweike , Oken Emily
Published: August 2018

Background:

Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up.

Goals:

Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up.

Materials and Methods:

We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases).

Results:

The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60).

Conclusions:

Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.
Comparison of Complication Rates of Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters in Pediatric Patients*
Authors: Noonan Patrick J. , Hanson Sheila J. , Simpson Pippa M. , Dasgupta Mahua , Petersen Tara L.
Published: August 2018

Objectives:

The purpose of our study is to compare the rate of central line–associated blood stream infections and venous thromboembolism in central venous catheters versus peripherally inserted central catheters in hospitalized children. There is a growing body of literature in adults describing an increased rate of venous thromboembolisms and similar rates of central line–associated blood stream infection associated with peripherally inserted central catheters versus central venous catheters. It is not known if the rate of central line–associated blood stream infection and venous thromboembolism differs between peripherally inserted central catheters and central venous catheters in children. Based on current adult literature, we hypothesize that central line–associated blood stream infection rates for peripherally inserted central catheters and central venous catheters will be similar, and the rate of venous thromboembolism will be higher for peripherally inserted central catheters versus central venous catheters.

Design:

This is a cohort study using retrospective review of medical records and prospectively collected hospital quality improvement databases.

Setting:

Quaternary-care pediatric hospital from October 2012 to March 2016.

Patients:

All patients age 1 day to 18 years old with central venous catheters and peripherally inserted central catheters placed during hospital admission over the study dates were included. Central venous catheters that were present upon hospital admission were excluded. The primary outcomes were rate of central line–associated blood stream infection and rate of venous thromboembolism.

Interventions:

None.

Measurements and Main Results:

Of 2,709 catheters included in the study, 1,126 were peripherally inserted central catheters and 1,583 were central venous catheters. Peripherally inserted central catheters demonstrated a higher rate of both infection and venous thromboembolism than central venous catheters in all reported measures. In multivariable analysis, peripherally inserted central catheters had increased association with central line–associated blood stream infection (odds ratio of 3.15; 95% CI, 1.74–5.71; p = 0.0002) and increased association with venous thromboembolism (odds ratio of 2.71; 95% CI, 1.65–4.45; p < 0.0001) compared with central venous catheters.

Conclusions:

Rates of central line–associated blood stream infection and venous thromboembolism were higher in hospitalized pediatric patients with peripherally inserted central catheters as compared to central venous catheters. Our study confirms the need for further investigation into the safety of central access devices to assist in proper catheter selection.
Clustering Analysis to Explore Cohorts in Comorbid Patients
Authors: Karkare Rasika
Published: August 2018

1.

Multimorbidities are associated with significant burden on the healthcare system and the lack of accurate and pertinent statistical exploratory techniques have often limited their analysis. Here we employ exploratory hierarchal agglomerative clustering (HAC) of multimorbidities in the inpatient population in the state of Ohio. The examination exposed the presence of ten discrete, clinically pertinent groups of multimorbidities within the Ohio inpatient population. This method offers an assessable empirical exploration of the multimorbidities present in a specific geographic populace.
Direct estimation of HDL-mediated cholesterol efflux capacity from serum
Authors: Kuusisto Sanna , Holmes Michael V. , Ohukainen Pauli , Kangas Antti J. , Karsikas Mari , Tiainen Mika , Perola Markus , Salomaa Veikko , Kettunen Johannes , Ala-Korpela Mika
Published: August 2018

High-density lipoprotein mediated cholesterol efflux capacity (HDL-CEC) is a functional attribute that may have a protective role in atherogenesis. However, the estimation of HDL-CEC is based on in vitro cell assays that are laborious and hamper large-scale phenotyping. Here, we present a cost-effective high-throughput nuclear magnetic resonance (NMR) spectroscopy method to estimate HDL-CEC directly from serum. We applied the new method in a population-based study of 7,603 individuals including 574 who developed incident coronary heart disease (CHD) during 15 years of follow-up, making this the largest quantitative study for HDL-CEC. As estimated by NMR-spectroscopy, a 1-SD higher HDL-CEC was associated with a lower risk of incident CHD (hazards ratio 0.86; 95%CI 0.79-0.93, adjusted for traditional risk factors and HDL-C). These findings are consistent with published associations based on in vitro cell assays. These corroborative large-scale findings provide further support for a potential protective role of HDL-CEC in CHD, and substantiate this new method and its future applications.
Designing a Study of Correlates of Risk for Ebola Vaccination
Authors: Elizabeth Halloran M. , Longini Ira M. , Gilbert Peter B.
Published: August 2018

The rVSV Ebola vaccine was shown to be very efficacious in a novel ring vaccination trial in Guinea. However, no correlates of vaccine protection have been established for Ebola vaccines. Several Ebola vaccine candidates are available, but conducting randomized trials of additional candidates in outbreak situations has become difficult. Establishing correlates of vaccine protection would be useful in helping vaccine candidates become licensed. In this note, we explore power and sample calculations to study potential correlates of risk (protection) during an Ebola vaccination campaign in an outbreak situation under a number of assumptions. At an overall vaccine efficacy of 75%, 50 Ebola endpoints in the vaccinees provided good power. At an overall vaccine efficacy of 90%, 20 Ebola endpoints gave good power under certain assumptions. In the May – July 2018 Ebola outbreak in DRC, over 3000 individuals were vaccinated, with no reported cases in vaccinated individuals. To be feasible, this type of study need Ebola endpoints in vaccinated individuals.
Mangrove vegetation inspires a new approach to protect shorelines
Authors: Segmaier Robert , Staggs Stephanie , Palmer Sarah
Published: August 2018

I. Abstract

Mangroves are found worldwide across the rivers and coastlines in tropical regions. They are robust against storm surges and tsunamic for a long time. The roots have the most contributions for their resiliency and therefore can be inspired for future manmade structures. The motion of water in riverine mangrove forest is expected to be impacted by mangrove roots, which in turn disturb the transport of nutrients, contaminants, and residues in these systems. In this paper, a facile method for protecting shoreline is described and review and the significant impact of this method were reviewed. Bioinspired simplified models as and obstruction to water currents in shorelines, and coastal areas are presented. It was found that Mangrove roots produce complex flow structure interactions with their environment, which affect the nutrient, habitat and aquatic animals. Analysis of the flow structure behind the roots extend to a broad range of mangrove-inspired applications and provide understandings into flows that are more complex and more indicative of the flows encountered in the unidirectional riverine flow.
Calicivirus VP2 forms a portal to mediate endosome escape
Authors: Conley Michaela , McElwee Marion , Azmi Liyana , Gabrielsen Mads , Byron Olwyn , Goodfellow Ian G. , Bhella David
Published: August 2018

To initiate the infectious process, many viruses enter their host cells by triggering endocytosis following receptor engagement. The mechanism by which non-enveloped viruses, such as the caliciviruses, escape the endosome is however poorly understood. TheCaliciviridaeinclude many important human and animal pathogens, most notably norovirus, the cause of winter vomiting disease. Here we show that VP2, a minor capsid protein encoded by all caliciviruses, forms a large portal assembly at a unique three-fold symmetry axis following receptor engagement. This feature surrounds an open pore in the capsid shell. We hypothesise that the VP2 portal complex is the means by which the virus escapes the endosome, pene-trating the endosomal membrane to release the viral genome into the cytoplasm. Cryogenic electron microscopy (cryoEM) and asymmetric reconstruction were used to investigate structural changes in the capsid of feline calicivirus (FCV) that occur when the virus binds to its cellular receptor junctional adhesion molecule-A (fJAM-A). Near atomic-resolution structures were calculated for the native virion alone and decorated with soluble receptor fragments. We present atomic models of the major capsid protein VP1 in the presence and absence of fJAM-A, revealing the contact interface and conformational changes brought about by the interaction. Furthermore, we have calculated an atomic model of the portal protein VP2 and revealed the structural changes in VP1 that lead to pore formation. While VP2 was known to be critical for the production of infectious virus, its function has been hitherto undetermined. Our finding that VP2 assembles a portal that is likely responsible for endosome escape represents a major step forward in our understanding of both theCaliciviridaeand icosahedral RNA containing viruses in general.
DeepCAPE: a deep convolutional neural network for the accurate prediction of enhancers
Authors: Chen Shengquan , Gan Mingxin , Lv Hairong , Jiang Rui
Published: August 2018

The establishment of a landscape of enhancers across human cells is crucial to deciphering the mechanism of gene regulation, cell differentiation, and disease development. High-throughput experimental approaches, though having successfully reported enhancers in typical cell lines, are still too costly and time consuming to perform systematic identification of enhancers specific to different cell lines under a variety of disease status. Existing computational methods, though capable of predicting regulatory elements purely relying on DNA sequences, lack the power of cell line-specific screening. Recent studies have suggested that chromatin accessibility of a DNA segment is closely related to its potential function in regulation, and thus may provide useful information in identifying regulatory elements. Motivated by the above understanding, we integrate DNA sequences and chromatin accessibility data to accurately predict enhancers in a cell line-specific manner. We proposed DeepCAPE, a deep convolutional neural network to predict enhancers via the integration of DNA sequences and DNase-seq data. We demonstrate that our model not only consistently outperforms existing methods in the classification of enhancers against background sequences, but also accurately predicts enhancers across different cell lines. We further visualize kernels of the first convolutional layer and show the match of identified sequence signatures and known motifs. We finally demonstrate the potential ability of our model to explain functional implications of putative disease-associated genetic variants and discriminate disease-related enhancers.
Multiple Exposures, Reinfection, and Risk of Progression to Active Tuberculosis
Authors: Ackley Sarah F. , Lee Robyn S. , Worden Lee , Zwick Erin , Porco Travis C. , Behr Marcel A. , Pepperell Caitlin S.
Published: August 2018

A recent study reported on a tuberculosis outbreak in a largely Inuit village. Among recently infected individuals, exposure to additional active cases was associated with an increasing probability of developing active disease within a year. Using binomial risk models, we evaluated two potential mechanisms by which multiple infections during the first year following initial infection could account for increasing disease risk with increasing exposures. In the reinfection model, multiple exposures have an independent risk of becoming an infection, and infections contribute independently to active disease. In the threshold model, disease risk follows a sigmoidal function with small numbers of exposures conferring a low risk of active disease and large numbers of exposures conferring a high risk. To determine the dynamic impact of reinfection during the early phase of infection, we performed simulations from a modified Reed-Frost model of TB dynamics following spread from an initial number of cases. We parameterized this model with the maximum likelihood estimates from the reinfection and threshold models in addition to the observed distribution of exposures among recent infections. We find that both models can plausibly account for the observed increase in disease risk with increasing exposures, but the threshold model confers a better fit than a nested model without a threshold (p=0.04). Our simulations indicate that multiple exposures during this critical time period can lead to dramatic increases in outbreak size. In order to decrease TB burden in high-prevalence settings, it may be necessary to implement measures aimed at preventing repeated exposures, in addition to preventing primary infection.
An open-source control system for in vivo fluorescence measurements from deep-brain structures
Authors: Owen Scott F. , Kreitzer Anatol C.
Published: August 2018

Background

Intracranial photometry through chronically implanted optical fibers is a widely adopted technique for measuring signals from fluorescent probes in deep-brain structures. The recent proliferation of bright, photo-stable, and specific genetically-encoded fluorescent reporters for calcium and for other neuromodulators has greatly increased the utility and popularity of this technique.

New Method

Here we describe an open-source, cost-effective, microcontroller-based solution for controlling optical components in an intracranial photometry system and processing the resulting signal.

Results

We show proof-of-principle that this system supports high quality intracranial photometry recordings from dorsal striatum in freely moving mice. A single system supports simultaneous fluorescence measurements in two independent color channels, but multiple systems can be integrated together if additional fluorescence channels are required. This system is designed to work in combination with either commercially available or custom-built optical components. Parts can be purchased for less than one tenth the cost of commercially available alternatives and complete assembly takes less than one day for an inexperienced user.

Comparison with Existing Method(s)

Currently available hardware draws on a variety of commercial, custom-built, or hybrid elements for both optical and electronic components. Many of these hardware systems are either specialized and inflexible, or over-engineered and expensive.

Conclusions

This open-source system increases experimental flexibility while reducing cost relative to current commercially available components. All software and firmware are open-source and customizable, affording a degree of experimental flexibility that is not available in current commercial systems.
Pairwise Efficiency: A new mathematical approach to qPCR data analysis increases the precision of the classical calibration curve assay
Authors: Panina Yulia , Germond Arno , David Brit G. , Watanabe Tomonobu M. ,   Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research(BDR)
Published: August 2018

The real-time quantitative polymerase chain reaction (qPCR) is routinely used for quantification of nucleic acids and is considered the gold standard in the field of relative nucleic acid measurements. The efficiency of the qPCR reaction is one of the most important parameters that needs to be determined, reported, and incorporated into data analysis in any qPCR experiment. The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines recognize the calibration curve as the method of choice for estimation of qPCR efficiency. The precision of this method has been reported to be between SD=0.007 (3 replicates) and SD=0.022 (no replicates). In this manuscript we present a novel approach to analysing qPCR data obtained by running a dilution series. Unlike previously developed methods, our method relies on a new formula that describes pairwise relationships between data points on separate amplification curves and thus operates extensive statistics (hundreds of estimations). The comparison of our method with classical calibration curve by Monte Carlo simulation shows that our approach can almost double the precision of efficiency and gene expression ratio estimations on the same dataset.
Genomic signatures of sympatric speciation with historical and contemporary gene flow in a tropical anthozoan
Authors: Titus Benjamin M. , Blischak Paul D. , Daly Marymegan
Published: August 2018

Sympatric diversification is increasingly thought to have played an important role in the evolution of biodiversity around the globe. However, an in situ sympatric origin for co-distributed taxa is difficult to demonstrate empirically because different evolutionary processes can lead to similar biogeographic outcomes-especially in ecosystems with few hard barriers to dispersal that can facilitate allopatric speciation followed by secondary contact (e.g. marine habitats). Here we use a genomic (ddRADseq), model-based approach to delimit a cryptic species complex of tropical sea anemones that are co-distributed on coral reefs throughout the Tropical Western Atlantic. We use coalescent simulations in fastsimcoal2 to test competing diversification scenarios that span the allopatric-sympatric continuum. We recover support that the corkscrew sea anemone Bartholomea annulata (Le Sueur, 1817) is a cryptic species complex, co-distributed throughout its range. Simulation and model selection analyses suggest these lineages arose in the face of historical and contemporary gene flow, supporting a sympatric origin, but an alternative secondary contact model also receives appreciable model support. Leveraging the genome of Exaiptasia pallida we identify five loci under divergent selection between cryptic B. annulata lineages that fall within mRNA transcripts or CDS regions. Our study provides a rare empirical, genomic example of sympatric speciation in a tropical anthozoan-a group that includes reef-building corals. Finally, these data represent the first range-wide molecular study of any tropical sea anemone, underscoring that anemone diversity is under described in the tropics, and highlighting the need for additional systematic studies into these ecologically and economically important species.
Eukaryotic Acquisition of a Bacterial Operon
Authors: Kominek Jacek , Doering Drew T. , Opulente Dana A. , Shen Xing-Xing , Zhou Xiaofan , De Virgilio Jeremy , Hulfachor Amanda B. , Kurtzman Cletus P. , Rokas Antonis , Hittinger Chris Todd
Published: August 2018

Operons are a hallmark of bacterial genomes, where they allow concerted expression of multiple functionally related genes as single polycistronic transcripts. They are rare in eukaryotes, where each gene usually drives expression of its own independent messenger RNAs. Here we report the horizontal operon transfer of a catecholate-class siderophore biosynthesis pathway from Enterobacteriaceae into a group of closely related yeast taxa. We further show that the co-linearly arranged secondary metabolism genes are actively expressed, exhibit mainly eukaryotic transcriptional features, and enable the sequestration and uptake of iron. After transfer to the eukaryotic host, several genetic changes occurred, including the acquisition of polyadenylation sites, structural rearrangements, integration of eukaryotic genes, and secondary loss in some lineages. We conclude that the operon genes were likely captured in the shared insect gut habitat, modified for eukaryotic gene expression, and maintained by selection to adapt to the highly-competitive, iron-limited environment.
HDAC Inhibitors Rescue Multiple Disease-Causing CFTR Variants
Authors: Anglès Frédéric , Hutt Darren M. , Balch William E.
Published: August 2018

Understanding the role of the epigenome in protein misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable respond of the disease population to any therapeutic. An ever-growing body of evidence has shown that histone deacetylase (HDAC) inhibitors (HDACi) can have significant benefit in correcting protein misfolding diseases that occur in response to both familial and somatic mutation. Cystic fibrosis (CF) is a familial autosomal recessive disease, caused by genetic diversity in the CF transmembrane conductance regulator (CFTR) gene, a cAMP-dependent chloride channel expressed at the apical plasma membrane of epithelial cells in multiple tissues. The potential utility of HDACi in correcting F508del as well as the over 2000 CF-associated variants remains controversial. To address this concern, we examined the impact of FDA-approved HDACi on the trafficking and function of a panel of CFTR variants. Our data reveal that panobinostat (LBH-589) and romidepsin (FK-228) provide functional correction of class II and III CFTR variants, restoring cell surface chloride channel activity in primary human bronchial epithelial (hBE) cells. We further demonstrate a synergistic effect of these HDACi with Vx809, that together can significantly restore channel activity for multiple CFTR variants. These data suggest that HDACi can serve to level the cellular playing field for correcting CF-causing mutations, a leveling effect that might also extend to other protein misfolding diseases.
Chronotopic Maps in Human Medial Premotor Cortex
Authors: Protopapa Foteini , Hayashi Masamichi J. , Kulashekhar Shrikanth , der Zwaag Wietske van , Battistella Giovanni , Murray Micah M. , Kanai Ryota , Bueti Domenica
Published: August 2018

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultra-high-field 7-Tesla functional magnetic resonance imaging, we show that in the medial premotor cortex of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface, so as to form chronomaps. The response of each portion in a chronomap is enhanced by preferred and neighboring durations and suppressed by non-preferred durations represented in distant portions of the map. These findings identify duration-sensitive tuning as a neural mechanism underlying the recognition of time and demonstrate for the first time that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.
EGFR Signalling Coordinates Patterning with Cell Survival DuringDrosophilaEpidermal Development
Authors: Crossman Samuel H. , Streichan Sebastian J. , Vincent Jean-Paul
Published: August 2018

Extensive apoptosis is often seen in patterning mutants, suggesting that tissues can detect and eliminate potentially harmful mis-specified cells. Here we show that the pattern of apoptosis in the embryonic epidermis ofDrosophilais not a response to fate mis-specification but can instead be explained by the limiting availability of pro-survival signalling molecules released from locations determined by patterning information. In wild type embryos, the segmentation cascade elicits the segmental production of several EGFR ligands, including the TGF-alpha, Spitz and the Neuregulin, Vein. This leads to an undulating pattern of signalling activity, which prevents expression of the pro-apoptotic genehidthroughout the epidermis. In segmentation mutants, where specific peaks of EGFR ligands fail to form, gaps in signalling activity appear, leading to coincidenthidupregulation and subsequent cell death. These data provide a mechanistic understanding of how cell survival, and thus appropriate tissue size, is made contingent on correct patterning.
miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2
Authors: Leigh Wesley , Liu Zhenxing , Nian Xiaoge , Zhang Yong
Published: August 2018

Circadian clocks control the timing of animal behavior rhythms to anticipate daily environmental changes. Fruit flies gradually increase their activity and reach a peak of activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3’ UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO and Fas2ΔmiR-210. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.

Author summary

Circadian clocks control the timing of animal physiology. Drosophila has been a powerful model in understanding the mechanisms of circadian regulation. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. Here we identify miR-210 as a critical regulator of evening anticipatory behavior. Depletion of miR-210 in flies advances evening anticipation. Futhermore, we identify the cell adhesion molecular Fas2 as miR-210’s target in circadian regulation. Fas2 abundance is increased in fly brain lacking of miR-210. Using CRISPR-Cas9 genome editing method, we deleted the miR-210 binding site on 3’ untranslated region of Fas2 and observed similar phenotype as miR-210 mutants. Altogether, our results indicate a novel mechanism of miR-210 in regulation of circadian anticipatory behavior through inhibition of Fas2.
Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: dose-efficacy studies upon oral administration
Authors: Tani Hideki , Komeno Takashi , Fukuma Aiko , Fukushi Shuetsu , Taniguchi Satoshi , Shimojima Masayuki , Uda Akihiko , Morikawa Shigeru , Nakajima Nozomi , Furuta Yousuke , Saijo Masayuki
Published: August 2018

Background

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a viral hemorrhagic fever with a high case fatality rate. Favipiravir was reported to be effective in the treatment of SFTSV infection in vivo in type I interferon receptor knockout (IFNAR-/-) mice at treatment dosages of both 60 mg/kg/day and 300 mg/kg/day for a duration of 5 days.

Methods

In this study, the efficacy of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day against SFTSV infection in an IFNAR-/- mouse infection model was investigated. IFNAR-/- mice were subcutaneously infected with SFTSV at a 1.0 × 106 50% tissue culture infectious dose followed by twice daily administration of favipiravir, comprising a total dose of either 120 mg/kg/day or 200 mg/kg/day. The treatment was initiated either immediately post infection or at predesignated time points post infection.

Results

All mice treated with favipiravir at dosages of 120 mg/kg/day or 200 mg/kg/day survived when the treatment was initiated at no later than 4 days post infection. A decrease in body weight of mice was observed when the treatment was initiated at 3–4 days post infection. Furthermore, all control mice died. The body weight of mice did not decrease when treatment with favipiravir was initiated immediately post infection at dosages of 120 mg/kg/day and 200 mg/kg/day.

Conclusions

Similar to the literature-reported peritoneal administration of favipiravir at 300 mg/kg/day, the oral administration of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day to IFNAR-/- mice infected with SFTSV was effective.

Author summary

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a generalized infectious disease with a high case fatality rate. Currently, no effective therapeutics for SFTS is available; therefore, the development of effective antiviral drugs is needed. Favipiravir exhibits antiviral activity against various RNA viruses, including SFTSV. The present study demonstrated the efficacy of favipiravir in the treatment of SFTSV infection in a lethal mouse model, when the dose was set similar to that approved for anti-influenza drug in humans by the Ministry of Health, Labour and Welfare, Japan. The present study suggests that favipiravir is a promising drug for the treatment of SFTSV infection.
Improvement of arthroscopic surgical performance using a new wide-angle arthroscope
Authors: Kwak Jae-Man , Kholinne Erica , Koh Kyoung Hwan , Jeon In-Ho
Published: August 2018

Background

We have developed a new arthroscope with a field of view of 150°. This requires less motion to maneuver, and the optical error is decreased. It also improves how novices learn arthroscopy. We hypothesized that surgical performance using this arthroscope is superior to a conventional arthroscope. This study tested the hypothesis using motion analysis and a new validated parameter, “dimensionless squared jolt” (DSJ).

Methods

We compared the surgical performance using between the wide-angle and the conventional arthroscope among 14 novice orthopedic residents who performed three standardized tasks three times with each arthroscope. The tasks simulated arthroscopic rotator cuff repair surgical skills. Their motion was analyzed using an optical tracking system. The differences in performance parameters, such as time taken, average acceleration of the hands (m/s2), the number of movements, and the total path length (m) including DSJ between the two arthroscopes, were investigated using paired t-tests.

Results

All the estimated values for the tasks using the 150° arthroscope were lower than those for the 105° arthroscope. There were statistically significant differences in performance between the two arthroscopes only for DSJ (p = 0.014) and average acceleration (p = 0.039).

Conclusions

DSJ and average acceleration are reliable parameters for representing hand-eye coordination. The surgical performance of novice arthroscopists was better with the new wide-angle arthroscope than with the conventional arthroscope.
Acute muscle fatigue and CPR quality assisted by visual feedback devices: a randomizedcrossover simulation trial
Authors: Abelairas-Gómez Cristian , Rey Ezequiel , González-Salvado Violeta , Mecías-Calvo Marcos , Rodríguez-Ruiz Emilio , Rodríguez-Núñez Antonio
Published: August 2018

Objective

To analyse the acute muscular fatigue (AMF) in triceps brachii and rectus abdominis during compression-only and standard cardiopulmonary resuscitation (CPR) performed by and certified basic life support providers.

Methods

Twenty-six subjects were initially recruited and randomly allocated to two study groups according to the muscles analysed; eighteen finally met the inclusion criteria (nine in each group). Both groups carried out two CPR tests (compression-only and standard CPR) of 10 min divided into five 2-min intermittent periods. The ventilation method was freely chosen by each participant (mouth-to-mouth, pocket-mask or bag-valve-mask). CPR feedback was provided all the time. AMF was measured by tensiomyography at baseline and after each 2-min period of the CPR test, in triceps brachii or rectus abdominis according to the study group.

Results

Rectus abdominis’ contraction time increased significantly during the fifth CPR period (p = 0.020). Triceps brachii’s radial muscle belly displacement (p = 0.047) and contraction velocity (p = 0.018) were lower during compression-only CPR than during standard CPR. Participants who had trained previously with feedback devices achieved better CPR quality results in both protocols. Half of participants chose bag-valve-mask to perform ventilations but attained lower significant ventilation quality than the other subjects.

Conclusions

Compression-only CPR induces higher AMF than standard CPR. Significantly higher fatigue levels were found during the fifth CPR test period, regardless of the method. Adequate rescuer’s strength seems to be a requisite to take advantage of CPR quality feedback devices. Training should put more emphasis on the quality of ventilation during CPR.
Large scale changes in host methylation patterns induced by IncA/C plasmid transformation inVibrio cholerae
Authors: Wang Ruibai , Wan Kanglin
Published: August 2018

DNA methylation is a central epigenetic modification and has diverse biological functions in eukaryotic and prokaryotic organisms alike. The IncA/C plasmid genomes are approximately 150kb in length and harbour three methylase genes, two of which demonstrate cytosine specificity. Transformation of theVibrio choleraestrain C6706 with the IncA/C plasmid pVC211 resulted in a significant relabelling of the methylation patterns on the host chromosomes. The new methylation patterns induced by transformation with IncA/C plasmid were accepted by the restriction enzymes of the host’s restriction modification (RM) system. These data uncover a novel mechanism by which plasmids can be compatible with a host’s RM system and suggest a possible reason that plasmids of the IncA/C family are broad-host-range.

Author summary

Antibiotic resistance of bacteria is a growing serious problem worldwidely and the horizontal transfer of multi-drug resistance genes mediated by plasmids within and between species of bacteria is the main reason. In the researches of multi-drug resistance ofVibrio cholerae, I have isolated several IncA/C plasmids. What impressed me most is their ability to accumulate the resistant genes. Moreover, they can transfer with high frequency and are stable in several bacterial species. There are at least three Tra regions on the IncA/C plasmid which containing components of the Type 4 Secretion System and are important for conjugative transfer of plasmids. So the horizontal transfer ability of IncA/C plasmids is reasonable. There are three methylase genes on the small genome of IncA/C plasmids, which demonstrate cytosine specificity and are seldom in bacteria. Their modification target and roles are interesting. Here, we analysed the methylation profiles of the hostV. choeraeinduced by the plasmid pVC211 and found that they were completely changed. In addition to replicons, this may be a novel mechanism that plasmid cross the barrier of the host’s RM system and become broad-host range. Changing the activity of methylase in IncA/C plasmids may be a new way to affect the stability of IncA/C plasmids to eliminate these multidrug-resistant plasmids from bacteria.
Local distortion and octahedral tilting in BaCe
x
Ti1−x
O3 perovskite
Authors: Confalonieri Giorgia , Buscaglia Vincenzo , Capitani GianCarlo , Canu Giovanna , Rotiroti Nicola , Bernasconi Andrea , Pavese Alessandro , Dapiaggi Monica
Published: August 2018

Ceramics with perovskite structure and composition BaCe
x
Ti1−x
O3 (x = 0.02–0.30) show a progressive evolution with increasing x, from the long-range polar order of ferroelectric BaTiO3 to the short-range polar order typical of relaxors. The ionic size mismatch between Ti4+ and Ce4+ determines strong local strains which have a significant impact on dielectric properties and phase transitions. The pair distribution function, coupled with transmission electron microscopy analysis, was applied to study the local structure. Because of the inner B-cation sizes, the superposition of rigid B—O octahedra with different volumes is not compatible with the construction of an ideal perovskite structure. In this light, local structure can be described by an original model which allows (i) different Ti—O and Ce—O distances and (ii) the typical distortions of the two end members: off-center displacement of Ti occurring in BaTiO3 and octahedral tilt in BaCeO3. The results show a clear difference, in terms of volumes, between oxygen octahedra with titanium and those related to cerium. In addition, the inclusion of cerium causes a tilt of its oxygen cage, as occurs in pure BaCeO3, creating contra-rotations and distortions of the octahedra containing titanium. This complex arrangement entails a substantial distortion, increasing as a function of cerium amount, which strongly influences the directions of titanium displacements, their local correlation and consequently their long-range cooperative effects.
Effects of energy spread on brightness and coherence of undulator sources
Authors: Geloni Gianluca , Serkez Svitozar , Khubbutdinov Ruslan , Kocharyan Vitali , Saldin Evgeni
Published: August 2018

The (spectral) brightness for partially transverse coherent sources such as synchrotron radiation and free-electron laser sources can be defined as the maximum of the Wigner distribution. Then, the brightness includes information on both coherence and wavefront characteristics of the radiation field. For undulator sources, it is customary to approximate the single-electron electric field at resonance with a Gaussian beam, leading to great simplifications. Attempts to account for the modified spatial and angular profile of the undulator radiation in the presence of detuning due to energy spread, currently build on the simplified brightness expression derived under the assumption of Gaussian beams. The influence of energy spread on undulator radiation properties is becoming important in view of diffraction-limited rings with ultralow emittance coming on-line. Here the effects of energy spread on the brightness of undulator radiation at resonance are discussed, as well as relevant relations with coherence properties.
Soft X-ray refractive index by reconciling total electron yield with specular reflection: experimental determination of the optical constants of graphite
Authors: Jansing C. , Wahab H. , Timmers H. , Gaupp A. , Mertins H.-C.
Published: August 2018

The complex refractive index of many materials is poorly known in the soft X-ray range across absorption edges. This is due to saturation effects that occur there in total-electron-yield and fluorescence-yield spectroscopy and that are strongest at resonance energies. Aiming to obtain reliable optical constants, a procedure that reconciles electron-yield measurements and reflection spectroscopy by correcting these saturation effects is presented. The procedure takes into account the energy- and polarization-dependence of the photon penetration depth as well as the creation efficiency for secondary electrons and their escape length. From corrected electron-yield spectra the absorption constants and the imaginary parts of the refractive index of the material are determined. The real parts of the index are subsequently obtained through a Kramers–Kronig transformation. These preliminary optical constants are refined by simulating reflection spectra and adapting them, so that measured reflection spectra are reproduced best. The efficacy of the new procedure is demonstrated for graphite. The optical constants that have been determined for linearly polarized synchrotron light incident withp- ands-geometry provide a detailed and reliable representation of the complex refractive index of the material near π- and σ-resonances. They are also suitable for allotropes of graphite such as graphene.