bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the “Sugarcane Chewing” Concept as the Directionality of Motor Neurotizer Selection for Facial Paralysis Reconstruction: Chang Gung Experiences
Authors: Chuang David Chwei-Chin , Lu Johnny Chuieng-Yi , Chang Tommy Nai-Jen , Hamdi Sakarya Ahmet
Published: May 2019

Background:

Facial paralysis and postparalysis facial synkinesis both cause severe functional and aesthetic deficits. Functioning free muscle transplantation is the authors’ preferred method for reconstructing both deformities.

Methods:

From 1985 to 2017, a total of 392 patients underwent 403 gracilis functioning free muscle transplantations for facial reanimation. Different motor neurotizers were used: cross-face nerve graft (74 percent), spinal accessory nerve (17 percent), and masseter nerve (8 percent). Smile excursion score, cortical adaptation stage, patient questionnaire, Hadlock lip excursion, and the Terzis evaluation systems were used to assess outcomes.

Results:

For smile excursion score, the spinal accessory and masseter nerve groups showed higher scores than the cross-face nerve graft group in the first 2 years, but no difference by 3-year follow-up. For cortical adaptation stage, nearly all cross-face nerve graft patients achieved stage IV or V spontaneity, the spinal accessory nerve group achieved at least stage III (independent) movement, but individuals in the masseter nerve group achieved only stage III or less. The cross-face nerve graft group also achieved higher scores according to the Hadlock system and the Terzis evaluation system compared with the other two groups.

Conclusions:

The concept of “sugarcane chewing” where the sweetness is the least at the tail but the most at the head can be simply applied for surgeons and patients in weighing the benefits and drawbacks during the motor neurotizer selection. Cross-face nerve graft–innervated gracilis is analogous to chewing sugarcane from tail to head; despite lower outcome measures earlier, it yields the highest scores at 3 years postoperatively. Masseter-innervated gracilis is akin to chewing sugarcane from head to tail, with greater outcome scores initially but little improvement at longer follow-up. Spinal accessory–innervated gracilis results fall in between these two groups.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A Critical Assessment of the Linear No-Threshold Hypothesis
Authors: Colletti Patrick M.
Published: May 2019

The Linear No-Threshold (LNT) hypothesis regarding low-level radiation is based on expert opinion. As more experts critically evaluate the absence of convincing evidence supporting the LNT hypothesis, the more likely we will recognize that LNT may create more risk than it mitigates.
MHC-mismatched Allotransplantation of Induced Pluripotent Stem Cell-derived Cardiomyocyte Sheets to Improve Cardiac Function in a Primate Ischemic Cardiomyopathy Model
Authors: Kashiyama Noriyuki , Miyagawa Shigeru , Fukushima Satsuki , Kawamura Takuji , Kawamura Ai , Yoshida Shohei , Eiraku Seiko , Harada Akima , Matsunaga Keiko , Watabe Tadashi , Toda Koichi , Hatazawa Jun , Sawa Yoshiki
Published: May 2019

Background.

Although allogeneic-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) exhibit potential in cardiomyogenesis for heart failure, whether major histocompatibility complex (MHC)-matched allogenic iPSC implantation (MMAI) minimizes immune rejection for cell survival or functional recovery remains unknown. We herein explored whether MMAI with an iPSC-CM sheet is stable for a longer period and therapeutically more effective than MHC-mismatched AI in a primate ischemic cardiomyopathy model.

Methods.

Green fluorescent protein-transfected iPSC-CM sheets, derived from cynomolgus macaques with homozygous MHC haplotypes ‘‘HT1,’’ were transplanted on the left ventricle, generated by ligating the left anterior descending artery for 2 weeks in an ischemic model with or without heterozygous HT1 as MMAI and MHC-mismatched AI. Sham models were made by opening the chest at 14 days after left anterior descending ligation without any treatment.

Results.

Stereomicroscopy revealed that at 4 months after transplantation, green fluorescent protein intensity was higher in the MMAI group than in the MHC-mismatched AI group and the sham group. Immunohistochemistry staining revealed that host immune reaction with CD3-positive cells was stronger in MHC-mismatched AI than in MMAI at 3 months. Cardiac function improved both in MMAI and MHC-mismatched AI at 1 month after transplantation and was preserved until 6 months, whereas in the sham group, functional deterioration progressed over time.

Conclusions.

Although MHC-homo-iPSCs are preferred to avoid immune rejection, MHC-mismatched iPSC-CMs can also induce comparable cardiac functional recovery at late follow-up, suggesting that MHC-mismatched iPSC-based cardiac regenerative therapy with immunosuppressants is a feasible option for treating heart failure in clinical settings.
Defining a Willingness-to-transplant Threshold in an Era of Organ Scarcity: Simultaneous Liver–kidney Transplant as a Case Example
Authors: Cheng Xingxing S. , Goldhaber-Fiebert Jeremy , Tan Jane C. , Chertow Glenn M. , Kim W. Ray , Wall Anji E.
Published: May 2019

Background.

Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multiorgan transplant, wherein a patient with multiorgan disease receives >1 organ from the same donor. Current allocation schemes give priority to multiorgan recipients compared with single-organ transplant recipients, which raise ethical questions regarding equity and utility.

Methods.

We use simultaneous liver and kidney (SLK) transplant, a type of multiorgan transplant, as a case study to examine the tension between equity and utility in multiorgan allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold.

Results.

We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives.

Conclusions.

We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.
Quantifying the hidden costs of imperfect detection for early detection surveillance
Authors: Mastin Alexander J. , van den Bosch Frank , van den Berg Femke , Parnell Stephen R.
Published: May 2019

The global spread of pathogens poses an increasing threat to health, ecosystems and agriculture worldwide. As early detection of new incursions is key to effective control, new diagnostic tests that can detect pathogen presence shortly after initial infection hold great potential for detection of infection in individual hosts. However, these tests may be too expensive to be implemented at the sampling intensities required for early detection of a new epidemic at the population level. To evaluate the trade-off between earlier and/or more reliable detection and higher deployment costs, we need to consider the impacts of test performance, test cost and pathogen epidemiology. Regarding test performance, the period before new infections can be first detected and the probability of detecting them are of particular importance. We propose a generic framework that can be easily used to evaluate a variety of different detection methods and identify important characteristics of the pathogen and the detection method to consider when planning early detection surveillance. We demonstrate the application of our method using the plant pathogen
Phytophthora ramorum
in the UK, and find that visual inspec-tion for this pathogen is a more cost-effective strategy for early detection surveillance than an early detection diagnostic test.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Outbreak analytics: a developing data science for informing the response to emerging pathogens
Authors: Polonsky Jonathan A. , Baidjoe Amrish , Kamvar Zhian N. , Cori Anne , Durski Kara , Edmunds W. John , Eggo Rosalind M. , Funk Sebastian , Kaiser Laurent , Keating Patrick , de Waroux Olivier le Polain , Marks Michael , Moraga Paula , Morgan Oliver , Nouvellet Pierre , Ratnayake Ruwan , Roberts Chrissy H. , Whitworth Jimmy , Jombart Thibaut
Published: May 2019

Despite continued efforts to improve health systems worldwide, emerging pathogen epidemics remain a major public health concern. Effective response to such outbreaks relies on timely intervention, ideally informed by all available sources of data. The collection, visualization and analysis of outbreak data are becoming increasingly complex, owing to the diversity in types of data, questions and available methods to address them. Recent advances have led to the rise ofoutbreak analytics, an emerging data science focused on the technological and methodological aspects of the outbreak data pipeline, from collection to analysis, modelling and reporting to inform outbreak response. In this article, we assess the current state of the field. After laying out the context of outbreak response, we critically review the most common analytics components, their inter-dependencies, data requirements and the type of information they can provide to inform operations in real time. We discuss some challenges and opportunities and conclude on the potential role of outbreak analytics for improving our understanding of, and response to outbreaks of emerging pathogens.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control‘. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Context matters: using reinforcement learning to develop human-readable, state-dependent outbreak response policies
Authors: Probert W. J. M. , Lakkur S. , Fonnesbeck C. J. , Shea K. , Runge M. C. , Tildesley M. J. , Ferrari M. J.
Published: May 2019

The number of all possible epidemics of a given infectious disease that could occur on a given landscape is large for systems of real-world complexity. Furthermore, there is no guarantee that the control actions that are optimal, on average, over all possible epidemics are also best for each possible epidemic. Reinforcement learning (RL) and Monte Carlo control have been used to develop machine-readable context-dependent solutions for complex problems with many possible realizations ranging from video-games to the game of Go. RL could be a valuable tool to generate context-dependent policies for outbreak response, though translating the resulting policies into simple rules that can be read and interpreted by human decision-makers remains a challenge. Here we illustrate the application of RL to the development of context-dependent outbreak response policies to minimize outbreaks of foot-and-mouth disease. We show that control based on the resulting context-dependent policies, which adapt interventions to the specific outbreak, result in smaller outbreaks than static policies. We further illustrate two approaches for translating the complex machine-readable policies into simple heuristics that can be evaluated by human decision-makers.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Structural basis for tetherin antagonism as a barrier to zoonotic lentiviral transmission
Authors: Buffalo Cosmo Z. , Stürzel Christina M. , Heusinger Elena , Kmiec Dorota , Kirchhoff Frank , Hurley James H. , Ren Xuefeng
Published: May 2019

Tetherin is a host defense that physically prevents escape of virions from the plasma membrane. Human tetherin lacks the motif DIWK antagonized by SIV, the antecedent of HIV. Here, we reconstituted the AP-2 clathrin adaptor complex with a simian tetherin and SIV Nef and determined its structure by cryo-EM. Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of MHC-I, CD3, and CD4, but overlaps the site for SERINC5 restricting viral infectivity. The structure explains the dependence of SIVs on the host tetherin DIWK sequence and the consequent barrier to human transmission.
Age at period cessation and trajectories of cardiovascular risk factors across mid and later life: a prospective cohort study
Authors: O’Keeffe Linda M , Kuh Diana , Fraser Abigail , Howe Laura D , Lawlor Debbie A , Hardy Rebecca
Published: May 2019

What is already known about this topic

Age at period cessation is associated with cardiovascular disease. Whether age at period cessation adversely affects change in conventional cardiovascular intermediates from mid to later life is not well understood.

What this study adds

Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impacts over the long term are small.

Objective

To examine the association between age at period cessation (by type of period cessation) and trajectories of anthropometry, blood pressure, lipids and HBA1c from midlife.

Design

Prospective cohort study of women recruited to the Medical Research Council National Survey of Health and Development (NSHD).

Setting

Population based prospective cohort study.

Participants

Women participating in NSHD with a known date of period cessation and at least one measure of each intermediate cardiovascular risk factor.

Exposures

Age at period cessation and type of period cessation (hysterectomy compared with natural menopause).

Outcomes

Repeated measures of systolic blood pressure, diastolic blood pressure, body mass index (BMI) and waist circumference (WC) from 36 to 69 years and repeated measures of triglyceride, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and glycated haemoglobin (HBA1c) from 53 to 69 years.

Results

We found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-c and HDL-c from 53 to 69 years and trajectories of blood pressure from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HBA1C, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null. For instance, the difference in log WC at age 69 per year increase in age at natural menopause was 0.003 (95% confidence interval, −0.0002, 0.01) while the difference per year increase in age at hysterectomy was −0.002 (95% CI, −0.005, 0.001).

Conclusion

How and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impacts over the long term are small.
DeepFly3D: A deep learning-based approach for 3D limb and appendage tracking in tethered, adult Drosophila
Authors: Günel Semih , Rhodin Helge , Morales Daniel , Campagnolo João , Ramdya Pavan , Fua Pascal
Published: May 2019

Studying how neural circuits orchestrate limbed behaviors requires the precise measurement of the positions of each appendage in 3-dimensional (3D) space. Deep neural networks can estimate 2-dimensional (2D) pose in freely behaving and tethered animals. However, the unique challenges associated with transforming these 2D measurements into reliable and precise 3D poses have not been addressed for small animals including the fly, Drosophila melanogaster. Here we present DeepFly3D, a software that infers the 3D pose of tethered, adult Drosophila—or other animals—using multiple camera images. DeepFly3D does not require manual calibration, uses pictorial structures to automatically detect and correct pose estimation errors, and uses active learning to iteratively improve performance. We demonstrate more accurate unsupervised behavioral embedding using 3D joint angles rather than commonly used 2D pose data. Thus, DeepFly3D enables the automated acquisition of behavioral measurements at an unprecedented level of resolution for a variety of biological applications.
Dynamic DNA structure states interact with the RNA editing enzyme ADAR1 to modulate fear extinction memory
Authors: Marshall Paul R. , Zhao Qiongyi , Li Xiang , Wei Wei , Malathi Abi , Zajaczkowski Esmi , Leighton Laura , Madugalle Sachithrani , Basic Dean , Wang Ziqi , Yin Jiayu , Liau Wei-Siang , Walkley Carl , Bredy Timothy W.
Published: May 2019

RNA modification has recently emerged as an important mechanism underlying gene diversity linked to behavioral regulation. The conversion of adenosine to inosine by the ADAR family of enzymes is a particularly important RNA modification as it impacts the physiological readout of protein-coding genes. However, not all variants of ADAR appear to act solely on RNA. ADAR1 binds directly to DNA when it is in a non-canonical, left handed, “Z” conformation, but little is known about the functional relevance of this interaction. Here we report that ADAR1 binds to Z-DNA in an activity-dependent manner and that fear extinction learning leads to increased ADAR1 occupancy at DNA repetitive elements, with targets adopting a Z-DNA structure at sites of ADAR1 recruitment. Knockdown of ADAR1 leads to an inability to modify a previously acquired memory trace and this is associated with a concomitant change in DNA structure and a decrease in RNA editing. These findings suggest a novel mechanism of learning-induced gene regulation whereby ADAR1 physically interacts with Z-DNA in order to mediate its effect on RNA, and both are required for memory flexibility following fear extinction learning.
Diversification or collapse of self-incompatibility haplotypes as outcomes of evolutionary rescue
Authors: Harkness Alexander , Goldberg Emma E. , Brandvain Yaniv
Published: May 2019

Self-incompatibility systems in angiosperms are exemplars of extreme allelic polymorphism maintained by long-term balancing selection. Pollen that shares an allele with the pollen recipient at the self-incompatibility locus is rejected, and this rejection favors rare alleles as well as preventing self-fertilization. Advances in molecular genetics reveal that an ancient, deeply conserved, and well-studied incompatibility system functions through multiple tightly linked genes encoding separate pollen-expressed F-box proteins and pistil-expressed ribonucleases. We show that certain recombinant haplotypes at the incompatibility locus can drive collapse in the number of incompatibility types. We use a modified evolutionary rescue model to calculate the relative probabilities of increase and collapse in number of incompatibility types given the initial collection of incompatibility haplotypes and the population rate of gene conversion. We find that expansion in haplotype number is possible when population size or the rate of gene conversion is large, but large contractions are likely otherwise. By iterating a Markov chain model derived from these expansion and collapse probabilities, we find that a stable haplotype number distribution in the realistic range of 10–40 is possible under plausible parameters. However, small or moderate-sized populations should be susceptible to substantial additional loss of haplotypes beyond those lost by chance during bottlenecks. The same processes that can generate many incompatibility haplotypes in large populations may therefore be crushing haplotype diversity in smaller populations.
Ex vivo 1H-MRS brain metabolic profiling in a two-hit model of schizophrenia-related alterations: effects of prenatal immune activation and peripubertal stress
Authors: Capellán Roberto , Moreno Mario , Orihuel Javier , Roura-Martínez David , Ucha Marcos , Ambrosio Emilio , Higuera-Matas Alejandro
Published: May 2019

Prenatal infections are environmental risk factors for neurodevelopmental disorders. In addition, traumatic experiences during adolescence in individuals exposed to infections during gestation could increase the risk of schizophrenia. Given the tremendous burden that these diseases pose on societies when they fully manifest, it is of the most crucial importance to discover potential markers of the disease in its early stages or even before its onset, so that therapeutic strategies may be implemented. In the present study, we combined a well-characterized two-hit model of schizophrenia-related symptoms with proton magnetic resonance spectroscopy to discover potential biomarkers. To this end, we i.p. injected 100 μg/kg/ml of lipopolysaccharide (LPS) or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to five episodes of stress or handling on alternate days during postnatal days (PND) 28 to 38. Once the animals reached adulthood (PND70), we evaluated prepulse inhibition (PPI). At PND90, we performed an ex vivo proton magnetic resonance spectroscopy study in the cortex and striatum. While we did not detect alterations in PPI at the age tested, we found neurochemical disturbances induced by LPS, stress or (more interestingly) their interaction. LPS decreased glucose levels in the cortex and striatum and altered glutamate, glutamine and N-acetylaspartate levels. Glutamate and glutamine levels in the left (but not right) striatum were differentially affected by prenatal LPS exposure in a manner that depended on stress experiences. These results suggest that alterations in the glutamate cycle in the striatum may predate the full emergence of disorders of the schizophrenic spectrum and could be used as early markers of the disease.
Competition among host-specific lineages ofPoecilochirus carabimites influences the extent of co-adaptation with theirNicrophorus vespilloidesburying beetle hosts
Authors: Sun Syuan-Jyun , Kilner Rebecca M.
Published: May 2019

Reciprocal selection between symbiotic organisms and their hosts can generate variations in local adaptation between them. Symbionts often form species complexes with lineages partially adapted to various hosts. However, it is unclear how interactions among these lineages influences geographic variation in host-symbiont local adaptation. We addressed this shortcoming with experiments on burying beetlesNicrophorus vespilloidesand their specialist phoretic mitePoecilochirus carabiin two adjacent woodlands. Burying beetles transport these mites to vertebrate carrion upon which they both reproduce.P. carabiappears to be a species complex, with distinct lineages that specialise on breeding alongside differentNicrophorusspecies. We found that in one wood (Gamlingay Woods),N. vespilloidescarries a mixture of mite lineages, with each lineage corresponding to one of the fourNicrophorusspecies that inhabits this wood. However, two burying beetle species coexist in neighbouring Waresley Woods and hereN. vespilloidespredominantly carries the mite lineage that favoursN. vespilloides. Mite lineage mixing alters the degree of local adaptation for bothN. vespilloidesand theP. carabimites, affecting reproductive success variably across different woodlands. In Gamlingay, mite lineage mixing reducedN. vespilloidesreproductive success, while experimentally purifying mites lineage enhanced it. The near pure lineage ofvespilloidesmites negligibly impacted WaresleyN. vespilloides. Mite reproductive success varied with host specificity: Gamlingay mites had greatest reproductive success on Gamlingay beetles, and performed less well with Waresley beetles. By contrast, Waresley mites had consistent reproductive success, regardless of beetle’s woodland of origin. We conclude that there is some evidence thatN. vespilloidesand its specific mite lineage have co-adapted. However, neitherN. vespilloidesnor its mite lineage adapted to breed alongside other mite lineages. This, we suggest, causes variation between Waresley and Gaminglay Woods in the extent of local adaptation betweenN. vespilloidesbeetles and theirP. carabimites.
Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine strains in anin cellulomodel of human blood-brain barrier
Authors: Khou Cécile , Díaz-Salinas Marco Aurelio , da Costa Anaelle , Préhaud Christophe , Jeannin Patricia , Afonso Philippe V. , Vignuzzi Marco , Lafon Monique , Pardigon Nathalie
Published: May 2019

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that JEV gets access to the central nervous system (CNS) as a consequence of a preceding inflammatory process which leads to the blood-brain barrier (BBB) disruption and viral neuroinvasion. However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross anin cellulohuman BBB model consisting of hCMEC/D3 human endothelial cells cultivated on permeable inserts above SK-N-SH human neuroblastoma cells. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post-addition. Furthermore, this BBB model was able to discriminate between the virulent RP9 and the vaccine SA14-14-2 strains, as demonstrated by the presence of almost 10 times more RP9 infectious particles that crossed the BBB than SA14-14 particles at a high MOI. Besides contributing to the understanding of early events in JEV neuroinvasion, thisin celluloBBB model represents a suitable and useful system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB at early times of neuroinvasion.
Knowledge-guided analysis of ‘omics’ data using the KnowEnG cloud platform
Authors: Blatti Charles , Emad Amin , Berry Matthew J. , Gatzke Lisa , Epstein Milt , Lanier Daniel , Rizal Pramod , Ge Jing , Liao Xiaoxia , Sobh Omar , Lambert Mike , Post Corey S. , Xiao Jinfeng , Groves Peter , Epstein Aidan T. , Chen Xi , Srinivasan Subhashini , Lehnert Erik , Kalari Krishna R. , Wang Liewei , Weinshilboum Richard M. , Song Jun S. , Jongeneel C. Victor , Han Jiawei , Ravaioli Umberto , Sobh Nahil , Bushell Colleen B. , Sinha Saurabh
Published: May 2019

We present KnowEnG, a free-to-use computational system for analysis of genomics data sets, designed to accelerate biomedical discovery. It includes tools for popular bioinformatics tasks such as gene prioritization, sample clustering, gene set analysis and expression signature analysis. The system offers ‘knowledge-guided’ data-mining and machine learning algorithms, where user-provided data are analyzed in light of prior information about genes, aggregated from numerous knowledge-bases and encoded in a massive ‘Knowledge Network’. KnowEnG adheres to ‘FAIR’ principles: its tools are easily portable to diverse computing environments, run on the cloud for scalable and cost-effective execution of compute-intensive and data-intensive algorithms, and are interoperable with other computing platforms. They are made available through multiple access modes including a web-portal, and include specialized visualization modules. We present use cases and re-analysis of published cancer data sets using KnowEnG tools and demonstrate its potential value in democratization of advanced tools for the modern genomics era.
Tightly regulated, yet flexible, directional switching mechanism of a rotary motor
Authors: Afanzar Oshri , Di Paolo Diana , Eisenstein Miriam , Levi Kohava , Plochowietz Anne , Kapanidis Achillefs N. , Berry Richard Michael , Eisenbach Michael
Published: May 2019

Biological switches are wide spread in many biological systems. Among them, the switch of the bacterial flagellar motor has generated much interest because it affects a mechanical process rather than a chemical reaction, it controls the direction of rotation of a rotary motor rather than being an on/off switch, and it is exceptionally ultrasensitive. Yet, the molecular mechanism underlying its function has remained unknown. Here we resolved unique features of this mechanism: On the one hand, it is tightly regulated by multiple means, involving three binding sites and two different covalent modifications, with the binding specificity being dictated by the type of covalent modification and by a strict binding sequence. On the other hand, it endows the motor with flexibility as it involves an intermediate stage of brief switches that provides a “go/no go” situation, in which the motor can either proceed to a stable rotation in the new direction or shift back to the original direction. This intermediate stage appears to be a means of the cell to produce angular deflection of swimming while maintaining directional persistence. Furthermore, we show by mathematical modeling that such a switching mechanism can provide ultrasensitivity. This unique combination of tight regulation, flexibility, and ultrasensitivity makes this switching mechanism of special interest.
Unique axon-to-soma signaling pathways mediate dendritic spine loss and hyper-excitability post-axotomy
Authors: Nagendran Tharkika , Taylor Anne Marion
Published: May 2019

Axon damage may cause axon regeneration, retrograde synapse loss, and hyper-excitability, all of which affect recovery following acquired brain injury. While axon regeneration is studied extensively, less is known about signaling mediating retrograde synapse loss and hyper-excitability, especially in long projection pyramidal neurons. To investigate intrinsic injury signaling within neurons, we use anin vitromicrofluidic platform that models dendritic spine loss and delayed hyper-excitability following remote axon injury. Our data show that sodium influx and reversal of sodium calcium exchangers (NCXs) at the site of axotomy, mediate dendritic spine loss following axotomy. In contrast, sodium influx and NCX reversal alone are insufficient to cause retrograde hyper-excitability. We found that calcium release from axonal ER is critical for the induction of hyper-excitability and inhibition loss. These data suggest that synapse loss and hyper-excitability are uncoupled responses following axon injury. Further, axonal ER may play a critical and underappreciated role in mediating retrograde hyper-excitability within the CNS.
In the presence of population structure: From genomics to candidate genes underlying local adaptation
Authors: Price Nicholas , Lopez Lua , Platts Adrian E. , Lasky Jesse R. , McKay John K.
Published: May 2019

Understanding the genomic signatures, genes, and traits underlying local adaptation of organisms to heterogeneous environments is of central importance to the field evolutionary biology. Mixed linear mrsodels that identify allele associations to environment, while controlling for genome-wide variation at other loci, have emerged as the method of choice when studying local adaptation. Despite their importance, it is unclear whether this approach performs better than identifying environmentally-associated SNPs without accounting for population structure. To examine this, we first use the mixed linear model GEMMA, and simple Spearman correlations, to identify SNPs showing significant associations to climate with and without accounting for population structure. Subsequently, using Italy and Sweden populations, we compare evidence of allele frequency differentiation (FST), linkage disequilibrium (LD), fitness variation, and functional constraint, underlying these SNPs. Using a lenient cut-off for significance, we find that SNPs identified by both approaches, and SNPs uniquely identified by Spearman correlations, were enriched at sites showing genomic evidence of local adaptation and function but were limited across Quantitative Trait Loci (QTL) explaining fitness variation. SNPs uniquely identified by GEMMA, showed no direct or indirect evidence of local adaptation, and no enrichment along putative functional sites. Finally, SNPs that showed significantly highFSTand LD, were enriched along fitness QTL peaks and cis-regulatory/nonsynonymous sites showing significant functional constraint. Using these SNPs, we identify genes underlying fitness QTL, and genes linking flowering time to local adaptation. These include a regulator of abscisic-acid (FLDH) and flowering time genesPIF3, FIO1, andCOL5.
Direct prediction of regulatory elements from partial data without imputation
Authors: Zhang Yu , Mahony Shaun
Published: May 2019

Genome segmentation approaches allow us to characterize regulatory states in a given cell type using combinatorial patterns of histone modifications and other regulatory signals. In order to analyze regulatory state differences across cell types, current genome segmentation approaches typically require that the same regulatory genomics assays have been performed in all analyzed cell types. This necessarily limits both the numbers of cell types that can be analyzed and the complexity of the resulting regulatory states, as only a small number of histone modifications have been profiled across many cell types. Data imputation approaches that aim to estimate missing regulatory signals have been applied before genome segmentation. However, this approach is computationally costly and propagates any errors in imputation to produce incorrect genome segmentation results downstream.

We present an extension to the IDEAS genome segmentation platform which can perform genome segmentation on incomplete regulatory genomics dataset collections without using imputation. Instead of relying on imputed data, we use an expectation-maximization approach to estimate marginal density functions within each regulatory state. We demonstrate that our genome segmentation results compare favorably with approaches based on imputation or other strategies for handling missing data. We further show that our approach can accurately impute missing data after genome segmentation, reversing the typical order of imputation/genome segmentation pipelines. Finally, we present a new 2D genome segmentation analysis of 127 human cell types studied by the Roadmap Epigenomics Consortium. By using an expanded set of chromatin marks that have been profiled in subsets of these cell types, our new segmentation results capture a more complex picture of combinatorial regulatory patterns that appear on the human genome.
Synthesis and characterization of two isostructural 3d–4f coordination compounds based on pyridine-2,6-dicarboxylic acid and 4,4′-bipyridine
Authors: Han Lizhi , Jin Longyi , Wang Enbo , Su Zhongmin
Published: May 2019

The design and synthesis of 3d–4f heterometallic coordination polymers have attracted much interest due to the intriguing diversity of their architectures and topologies. Pyridine-2,6-dicarboxylic acid (H2pydc) has a versatile coordination mode and has been used to construct multinuclear and heterometallic compounds. Two isostructural centrosymmetric 3d–4f coordination compounds constructed from pyridine-2,6-dicarboxylic acid and 4,4′-bipyridine (bpy), namely 4,4′-bipyridine-1,1′-diium diaquabis(μ2-pyridine-2,6-dicarboxylato)tetrakis(pyridine-2,6-dicarboxylato)bis[4-(pyridin-4-yl)pyridinium]cobalt(II)dieuropium(III) octahydrate, (C10H10N2)[CoEu2(C10H9N2)2(C7H3NO4)6(H2O)2]·8H2O, (I), and 4,4′-bipyridine-1,1′-diium diaquabis(μ2-pyridine-2,6-dicarboxylato)tetrakis(pyridine-2,6-dicarboxylato)bis[4-(pyridin-4-yl)pyridinium]cobalt(II)diterbium(III) octahydrate, (C10H10N2)[CoTb2(C10H9N2)2(C7H3NO4)6(H2O)2]·8H2O, (II), were synthesized under hydrothermal conditions and characterized by IR and fluorescence spectroscopy, thermogravimetric analysis and powder X-ray diffraction. Both compounds crystallize in the triclinic space group P\overline{1}. The EuIII and TbIII cations adopt nine-coordinated distorted tricapped trigonal–prismatic geometries bridged by three pydc2− ligands. The CoII cation has a six-coordination environment formed by two pydc2− ligands, two bpy ligands and two coordinated water molecules. Adjacent molecules are connected by π–π stacking interactions to form a one-dimensional chain, which is further extended into a three-dimensional supramolecular network by multipoint hydrogen bonds.
Japanese surgical resource utilization in 2016
Authors: Nakata Yoshinori , Watanabe Yuichi , Narimatsu Hiroto , Yoshimura Tatsuya , Otake Hiroshi , Sawa Tomohiro
Published: May 2019

Purpose

The purpose of this paper is to examine from the viewpoint of resource utilization the Japanese surgical payment system which was revised in April 2016.

Design/methodology/approach

The authors collected data from surgical records in the Teikyo University electronic medical record system from April 1 till September 30, 2016. The authors defined the decision-making unit as a surgeon with the highest academic rank in the surgery. Inputs were defined as the number of medical doctors who assisted surgery, and the time of operation from skin incision to closure. An output was defined as the surgical fee. The authors calculated each surgeon’s efficiency score using output-oriented Charnes–Cooper–Rhodes model of data envelopment analysis. The authors compared the efficiency scores of each surgical specialty using the Kruskal–Wallis and the Steel method.

Findings

The authors analyzed 2,558 surgical procedures performed by 109 surgeons. The difference in efficiency scores was significant (p = 0.000). The efficiency score of neurosurgery was significantly greater than obstetrics and gynecology, general surgery, orthopedics, emergency surgery, urology, otolaryngology and plastic surgery (p<0.05).

Originality/value

The authors demonstrated that the surgeons’ efficiency was significantly different among their specialties. This suggests that the Japanese surgical reimbursement scales fail to reflect resource utilization despite the revision in 2016.
Nursing staff and patients’ length of stay
Authors: Moisoglou Ioannis , Galanis Petros , Meimeti Evangelia , Dreliozi Angeliki , Kolovos Petros , Prezerakos Panagiotis
Published: May 2019

Purpose

The purpose of this paper is to investigate the effect of nurse staffing, nurse education and work experience on patients’ length of stay (LOS) in the Greek public hospitals.

Design/methodology/approach

A cross-sectional study, with retrospective administrative data, was implemented. From all seven Regional Health Authorities of Greece, 25 general surgical units in 17 public hospitals participated in the study.

Findings

All over the hospitals were studied, 32,287 patients ⩾17 years old and 203 nursing staff, who were working in the study units, were included in the analysis. According to the multivariate linear regression model, increased years of experience as a nurse (b= −0.04, 95% CI= −0.06 to −0.02, p=0.001) and increased percentage of registered nurse to the total nursing staff (b= −1.18, CI= −1.88 to −0.47, p=0.03) were associated with decreased patient LOS.

Originality/value

This was the first extended study in Greece, which explored the relationship between nurse staffing, nurse education, work experience and the LOS. The role that nurse staffing play together with its characteristics in the provision toward the quality healthcare services has already been recognized worldwide. The findings revealed the great shortage of nursing staff and the significant correlation between the work experience and educational level to patients’ LOS.
An open source solution to a common collection problem: the Africa image and map portal
Authors: Partlow Mia , Quill Theresa , Djenno Mireille
Published: May 2019

Purpose

The purpose of this paper is to provide an overview of the Africa image and map portal (AIMP) project’s origins and development, along with its applications to date. This paper includes methods and a step-by-step appendix so that the project can be reproduced at other institutions.

Design/methodology/approach

AIMP was created with a suite of free and open source software, including QGIS, Mapbox.js and GitHub. Built around the concept of an interactive index map, AIMP allows for geographic searching of maps, posters and images from Indiana University’s (IU) African Studies collections. This paper presents a case study for the use of this geographic discovery tool at an academic library.

Findings

AIMP has allowed comparison of collection strengths with research interests of IU African Studies affiliates and to make strategic collection development decisions that will best serve the authors’ patrons. The instruction applications of AIMP are also full of potential. To date, the Librarian for African Studies has used the portal to familiarize faculty, as well as undergraduate and graduate students, with the range of image and map resources available to them, in a variety of settings.

Social implications

AIMP allows researchers around the world to discover materials through a geographic search, dramatically connecting and increasing access to and discoverability of these important collections. The use of free and open source geospatial software (foss4g) means that the interface does not rely on an institution’s proprietary software-licensing agreements, making it replicable for other institutions. This use of foss4g widens access to maps, spatial data, images and posters of Africa held by IUL to a global audience.

Originality/value

While interactive index maps are popular among map libraries, AIMP uniquely acts as a discovery portal for a variety of media, including images and posters. In this way, AIMP works to overcome institutional silos and increase discoverability of these important collections to a global audience.
Identification of a small RNA that directly controls the translation of the quorum sensing signal synthase gene rhlI in Pseudomonas aeruginosa
Authors: Chen Ronghao , Wei Xueying , Li Zhenpeng , Weng Yuding , Xia Yushan , Ren WenRan , Wang Xiangxiang , Jin Yongxin , Bai Fang , Cheng Zhihui , Jin Shouguang , Wu Weihui
Published: May 2019

The biofilm formation by Pseudomonas aeruginosa highly increases the bacterial resistance to antimicrobial agents and host immune clearance. The biofilm formation is positively regulated by two small RNAs, RsmY and RsmZ. Previously, we reported that mutation in the polynucleotide phosphorylase (PNPase) coding gene pnp increases the levels of RsmY/Z. However, in this study, we found that the biofilm formation is decreased in the pnp mutant, which is due to a defect in rhamnolipids production. The rhamnolipids production is regulated by the RhlI‐RhlR quorum sensing system. We found that PNPase influences the translation of RhlI through its 5′‐untranslated region (UTR) and identified that the sRNA P27 is responsible for the translational repression. In vitro translation experiments demonstrated that P27 directly represses the translation of the rhlI mRNA through its 5′UTR in an Hfq‐dependent manner. Point mutations in the rhlI 5′UTR or P27, which abolish the pairing between the two RNAs restore the rhlI expression and rhamnolipids production as well as the biofilm formation in the pnp mutant. Overall, our results reveal a novel layer of regulation of the Rhl quorum sensing system by the sRNA P27.
Subordinate reactions to ethical leaders’ abusive behavior: a multiple‐wave study
Authors: Wang Rong , Chan Darius K‐S
Published: May 2019

This paper examines the role of ethical leadership in mitigating the effects of abusive supervision and subsequent impact on employee outcomes including interaction justice, job attitudes and well‐being. We examined two sets of moderated mediating models to link positive and negative leader behaviors together by taking on a subordinate‐centric perspective. The first set stipulates that prior ethical leadership, as a moral licence, will reduce the negative impact of subsequent abusive supervision on interactional justice, which, in turn, will enhance subordinates’ job‐related attitudes and well‐being. The second set hypothesizes that prior ethical leadership will accentuate the importance of interactional justice, making subordinates more easily influenced by subsequent abusive supervision. Data were obtained from full‐time Chinese employees by using a three‐wave time lagged design (n = 223). The results generally supported our second hypothesized model. Specifically, interactional justice mediated the relations between abusive supervision and work outcomes. Moreover, prior ethical leadership moderated the interactional justice–work outcome relations as well as the indirect effect of abusive supervision on work outcomes via interactional justice.
Analysis of Pesticide Residue in Tomatoes by Carbon Nanotubes/β‐Cyclodextrin Nanocomposite Reinforced Hollow Fiber Coupled with HPLC
Authors: Ding Yawen , Song Xinyue , Chen Juan
Published: May 2019

For addressing the issues of pesticide residue analysis characterized by the trace levels of target analytes and the complexity of sample matrices, a selective extracting material, carbon nanotubes (CNTs)/β‐cyclodextrin (β‐CD) nanocomposite reinforced hollow fiber (HF), was developed. CNTs were chemically modified with β‐CD and then the resultant nanocomposite was immobilized into the wall pores and lumen of HF by sol‐gel technology. The reinforced HF was applied to direct‐immersion mode of solid phase microextraction for the determination of carbaryl and 1‐naphthol in tomatoes, coupled with high performance liquid chromatography. The proposed method provided 240‐ and 215‐fold enrichment factors, good linearity in the range of 0.6 to 600 ng/g and 0.2 to 600 ng/g, good repeatability with RSDs of 4.5% and 6.9%, and batch‐to‐batch reproducibility with RSDs of 7.4% and 8.3% for 1‐naphthol and carbaryl, respectively. Moreover, the low limits of detection at 0.05 and 0.15 ng/g for 1‐naphthol and carbaryl, respectively, along with the high recovery in the range of 84.2% to 108.9% were obtained. The results showed that the material combined the respective advantages of CNTs, β‐CD, and HF, thus, exhibiting efficient adsorption property, outstanding molecular recognition performance, and excellent sample clean‐up effect, and it is applicable for pesticide residue analysis in complex matrices.

Practical Application

The developed extracting material can be used for pesticide residue analysis of tomatoes. Pesticides, carbaryl, and 1‐naphthol were detected in tomatoes, the most popular vegetable grown and consumed globally. The results supported the necessity to monitor pesticide residue for public health.