bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing the Number of Certified Registered Nurses in an Emergency Department
Authors: Neira Paula M. , Maliszewski Barbara , Toledo RaniMaria , Borries Kimberly , Baptiste Diana-Lyn
Published: September 2016

Nationally, hospital emergency departments are met with challenges because of increasing patient demands, overcrowding, and the need to protect patient safety. It is imperative that frontline emergency department nurses are prepared to meet the complex needs of diverse patient populations by having appropriate continuing education, training, and institutional resources. Professional certification is associated with improved patient safety, higher organizational performance scores, professional growth, and credibility among nurses. The purpose of this article is to describe the process and outcome of a nursing professional development-practitioner-led intervention to promote professional certification among nurses in an urban adult emergency department while reducing overall cost of institutional support for certification preparation.
Caring for the Transgender Individual
Authors: Sedlak Carol A. , Veney Amy J. , Doheny Margaret O'Bryan
Published: September 2016

Issues about transgender individuals (TIs) as a disparate population are now being more openly discussed in the general public. However, healthcare providers often express feeling uncomfortable in interacting with TIs because they have not been educated about care of TIs and often base their care on insensitive stereotyping. The purpose of this informational article is to provide a foundation of knowledge for nurses and healthcare professionals for providing competent patient-centered care for TIs. Topics discussed include a description of the transgender population, commonly used terms to describe TIs, health risks and healthcare needs of TIs, and how to provide quality healthcare for TIs.
Application and Interpretation of Hierarchical Multiple Regression
Authors: Jeong Younhee , Jung Mi Jung
Published: September 2016

The authors reported the association between motivation and self-management behavior of individuals with chronic low back pain after adjusting control variables using hierarchical multiple regression (Jung & Jeong, 2016). This article describes details of the hierarchical regression applying the actual data used in the article by Jung and Jeong (2016), including how to test assumptions, run the statistical tests, and report the results.
The Experience of Long-Stay Parents in the ICU: A Qualitative Study of Parent and Staff Perspectives
Authors: Geoghegan Sophie , Oulton Kate , Bull Catherine , Brierley Joe , Peters Mark , Wray Jo
Published: September 2016

Objective:

Meeting the needs of parents of critically ill children is increasingly being recognized as an important factor in the child’s clinical outcome as well as the implications it has for future parenting. Little is specifically known about the experience of parents who have a child in the ICU for a prolonged period. Our objective was to understand the experiences of this group to assist in the identification of mechanisms for providing support.

Design:

Qualitative study based on semistructured interviews. Data were analyzed using the Framework approach.

Setting:

The study took place in a tertiary pediatric hospital containing three ICUs: PICU, cardiac ICU, and neonatal ICU (ICU will be used to encompass neonatal ICU, cardiac ICU, and PICU for the remainder of the article).

Subjects:

Seventeen members of staff and 26 parents of a child who had a long stay in one of the three ICUs.

Interventions:

Semistructured, tape-recorded interviews.

Measurements and Main Results:

Analyses identified two overarching themes, “parent process” and “parent/staff interface,” and six subthemes: adjustment, normalization/institutionalization, conflict, involvement in child’s care, individualized care, and transition. Themes have been modeled to account for the parental process during a long stay in the ICU and the potential implications for the relationships and interactions between parents and staff. Findings are presented from the data related to the parent process and parent/staff interface. Inclusion of an element in the model related to staff indicates where support mechanisms should be focused.

Conclusions:

Over time, long-stay families will likely become more familiar with the environment of the ICU, more knowledgeable about their child’s medical needs and more familiar with the staff looking after their child. This has a number of implications for staff working in the ICU.
Toxicological Emergencies in the Resuscitation Area of a Pediatric Emergency Department: A 12-Month Review
Authors: Beauchamp Gillian A. , Kerrey Benjamin T. , Mittiga Matthew R. , Rinderknecht Andrea S. , Yin Shan
Published: September 2016

Objective

Few studies of children with toxicological emergencies describe those undergoing acute resuscitation, and most describe exposures to single agents. We describe a 12-month sample of patients evaluated in the resuscitation area of a pediatric emergency department (ED) for a toxicological emergency.

Methods

We conducted a retrospective chart review of patients in a high-volume, academic pediatric ED. We identified patients evaluated in the ED resuscitation area for toxicological exposure and conducted structured chart reviews to collect relevant data. For all variables of interest, we calculated standard descriptive statistics.

Results

Of 2999 patients evaluated in the resuscitation area through 12 months (March 2009 to April 2010), we identified 80 (2.7%) whose primary ED diagnosis was toxicological. The mean age was 11.4 years. Eighty-six percent of patients were triaged to the resuscitation area for significantly altered mental status. The most frequent single exposures were ethanol (25%), clonidine (10%), and acetaminophen (5%). At least 1 laboratory test was performed for almost all patients (97%). Interventions performed in the resuscitation area included intravenous access placement (97%), activated charcoal (20%), naloxone (19%), and endotracheal intubation (12%). Eighty-two percent of patients were admitted to the hospital; 37% to the intensive care unit. No patients studied in this sample died and most received only supportive care.

Conclusions

In a high-volume pediatric ED, toxicological emergencies requiring acute resuscitation were rare. Ethanol and clonidine were the most frequent single exposures. Most patients received diagnostic testing and were admitted. Further studies are needed to describe regional differences in pediatric toxicological emergencies.
Factors Associated With High Frequency of Suicidal Ideation in Medically Ill Veterans
Authors: WENDELL JOEL , RATCLIFF CHELSEA G. , PRICE ELIZABETH , PETERSEN NANCY J. , DINAPOLI ELIZABETH A. , CULLY JEFFREY A.
Published: September 2016

Suicide is a leading cause of death, and rates are especially high among medically ill, older individuals. Health-related psychosocial correlates of suicidal ideation (SI) may be particularly important for medically ill older adults as they may clarify who may benefit from interventions to reduce SI. This study examined whether demographic, physical health, and/or health-related psychosocial factors were associated with high frequency of SI in older, medically ill Veterans experiencing elevated anxiety or depression. This cross-sectional study included 302 Veterans with (1) a cardiopulmonary condition and functional impairment and (2) elevated symptoms of depression and/or anxiety. Participants were classified as having either no, low, or high SI, based on self-reported ideation, from the Patient Health Questionnaire-9. SI was reported in 26.8% of the full sample and high SI was reported by 12.6% of participants. Logistic regression analyses predicting high versus no SI found the odds of high SI increased 4.7 times (95% confidence interval, 2.6–8.3) for each 1-unit increase in maladaptive coping and 4.1 times (95% confidence interval, 1.2–14.3) for each 1-unit increase in physical health severity/functional limitations. Older, medically ill Veterans with comorbid depression and/or anxiety frequently reported SI and were at greater risk of experiencing a high frequency of SI if they engaged in maladaptive coping strategies and/or had high levels of functional impairment. Effective interventions to reduce SI for this population should focus on reducing maladaptive coping and minimizing negative behavioral, cognitive, and emotional reactions to functional limitations.
Constant Observation of Suicidal Patients: The Intervention We Love to Hate
Authors: RUSS MARK J.
Published: September 2016

Constant observation (CO) of psychiatric inpatients at risk for suicidal behavior has been criticized in the literature because of the absence of demonstrable effectiveness, associated costs, staff and patient acceptance, and related issues. Our inability to demonstrate effectiveness, however, is an ethical conundrum that cannot readily be solved. Frequent and often vociferous references in the literature to the absence of an evidence base for this intervention carries the risk that CO may be underutilized in particular clinical circumstances with untoward results. A case is made for shifting focus from the lack of evidence supporting CO to agreement on an observation protocol that achieves the desired goal of maximizing patient safety. A sample protocol is presented.
Risks, Benefits, and Recommendations for Pastoral Care on Inpatient Psychiatric Units: A Systematic Review
Authors: PENNYBAKER STEVEN , HEMMING PATRICK , ROY DURGA , ANTON BLAIR , CHISOLM MARGARET S.
Published: September 2016

Objective:

A systematic review was conducted of the biomedical literature regarding pastoral care (PaC) providers on inpatient psychiatric units with the aim of answering 3 questions: (1) What are the risks and benefits of PaC providers’ presence on inpatient psychiatric units? (2) What are current recommendations for integration of PaC providers into a psychiatric team? and (3) What gaps exist in the literature?

Methods:

PubMed, PsycInfo, Embase, CINAHL, and Scopus were searched from the start of each database to July 9, 2014 using terms related to PaC providers and inpatient psychiatry. Two independent reviewers performed full-text reviews of each article identified by independent review of all titles/abstracts from the electronic search and by a hand search of articles included in reference lists. Inclusion criteria were: English-language article, published in a peer-reviewed journal, and focus on a PaC provider working in a psychiatric hospital setting. One author performed data extraction.

Results:

Forty-nine articles were identified by electronic (84%) and hand search (16%), 18 of which were evaluative studies: 5 qualitative and 13 quantitative. Most of the literature viewed integration of PaC providers in inpatient treatment teams as beneficial. Potential harms were noted and mitigation strategies suggested, including providing training to PaC providers concerning psychiatric illness, clearly defining roles, and enhancing team integration. None of the articles reported outcomes data.

Conclusions:

Psychiatric inpatients often have unmet spiritual needs. Although the literature suggests potential benefits of PaC providers for psychiatric inpatients, more rigorous studies are needed to establish these benefits as efficacious. The authors of this review recommend the cautious integration of PaC providers into the psychiatric inpatient care team.
Pyrotherapy for the Treatment of Psychosis in the 21st Century: A Case Report and Literature Review
Authors: ZUSCHLAG ZACHARY D. , LALICH CALLIE J. , SHORT EDWARD B. , HAMNER MARK , KAHN DAVID A.
Published: September 2016

The concept that fevers can improve the condition of patients with certain medical and psychiatric diseases dates back to Hippocrates. Over the centuries, it has been observed that fevers and infectious agents have been beneficial for a broad spectrum of diseases, including neurologic conditions such as epilepsy and psychiatric illnesses including melancholy and psychosis. Interest in the concept of fever as a treatment for disease, termed pyrotherapy or pyretotherapy, peaked in the late 1800s and early 1900s thanks to the Nobel Prize winning work of Julius Wagner-Jauregg for his studies with malaria therapy for general paralysis of the insane, now more commonly referred to as neurosyphilis. The use of inoculations of infectious agents for their fever-inducing effects in the treatment of neurosyphilis quickly spread throughout the world, and, by the 1920s, it was considered by many to be the treatment of choice for neurosyphilis as well as other psychotic disorders. However, with the discovery of penicillin for the treatment of syphilis, which coincided with the advent of convulsion-oriented practices including electroconvulsive therapy and insulin coma for the treatment of psychotic disorders, pyrotherapy soon lost favor among psychiatrists and, since the 1950s, it has largely been overlooked by the scientific community. In this article, the authors provide a brief literature review of the history of pyrotherapy and present a case report of a woman with schizoaffective disorder and severe psychotic symptoms who experienced a remarkable resolution of psychotic symptoms following an episode of bacteremia with high fever.
National Initiative to Prevent Suicide (NIPS): A New Proposal to Improve the Understanding and Prevention of Suicide
Authors: PRESKORN SHELDON H.
Published: September 2016

Suicide is a staggering, tragic, and growing cause of death in the United States. Despite a government-led 20-year effort, the suicide rate increased by 25% between 1999 and 2014. To prevent suicide, it is essential to understand the biological factors—genetic and epigenetic—and environmental factors that underlie it. To gain this increased understanding, the equivalent of the “War on Cancer” initiative is needed. The War on Cancer initiative, which began in the 1970s, has transformed the treatments and outcomes of cancer, and the same could occur with a similar initiative on suicide. This article proposes a National Initiative to Prevent Suicide (NIPS), with the first step being the establishment of a National Suicide Database (NSD). The NSD would be established by a government-private partnership much as was done by the National Cancer Institute in the War on Cancer. The NSD would be established under the auspices of the National Institute of Mental Health and the Centers for Disease Control and Prevention. Approximately $600 million are currently spent annually by taxpayers in the United States to support the medicolegal death investigation system, composed of 3137 county coroner or medical examiner offices across the country. In their investigation of deaths due to suicide, these offices collect extensive information, including biological samples, from the >40,000 deaths due to suicide that occur each year. The proposal presented in this column calls for this material to be stored in the NSD so that vetted government and public/private researchers can investigate the causes of suicide. This information will make possible the development of new methods, including laboratory evaluations, for assessing suicide risk as well as new treatments to prevent suicide. In support of this proposed new initiative, this article/proposal reviews the current medicolegal death investigation system and recent advances in our understanding of the biological basis of suicide. The time for action on this proposal is now.
Critical factors determining the quantification capability of matrix-assisted laser desorption/ionization– time-of-flight mass spectrometry
Authors: Wang Chia-Chen , Lai Yin-Hung , Ou Yu-Meng , Chang Huan-Tsung , Wang Yi-Sheng
Published: September 2016

Quantitative analysis with mass spectrometry (MS) is important but challenging. Matrix-assisted laser desorption/ionization (MALDI) coupled with time-of-flight (TOF) MS offers superior sensitivity, resolution and speed, but such techniques have numerous disadvantages that hinder quantitative analyses. This review summarizes essential obstacles to analyte quantification with MALDI-TOF MS, including the complex ionization mechanism of MALDI, sensitive characteristics of the applied electric fields and the mass-dependent detection efficiency of ion detectors. General quantitative ionization and desorption interpretations of ion production are described. Important instrument parameters and available methods of MALDI-TOF MS used for quantitative analysis are also reviewed.

This article is part of the themed issue ‘Quantitative mass spectrometry’.
Population-genomic insights into emergence, crop adaptation and dissemination of Pseudomonas syringae pathogens
Authors: Monteil Caroline L. , Yahara Koji , Studholme David J. , Mageiros Leonardos , Méric Guillaume , Swingle Bryan , Morris Cindy E. , Vinatzer Boris A. , Sheppard Samuel K.
Published: September 2016

Many bacterial pathogens are well characterized but, in some cases, little is known about the populations from which they emerged. This limits understanding of the molecular mechanisms underlying disease. The crop pathogen Pseudomonas syringae sensu lato has been widely isolated from the environment, including wild plants and components of the water cycle, and causes disease in several economically important crops. Here, we compared genome sequences of 45 P. syringae crop pathogen outbreak strains with 69 closely related environmental isolates. Phylogenetic reconstruction revealed that crop pathogens emerged many times independently from environmental populations. Unexpectedly, differences in gene content between environmental populations and outbreak strains were minimal with most virulence genes present in both. However, a genome-wide association study identified a small number of genes, including the type III effector genes hopQ1 and hopD1, to be associated with crop pathogens, but not with environmental populations, suggesting that this small group of genes may play an important role in crop disease emergence. Intriguingly, genome-wide analysis of homologous recombination revealed that the locus Psyr 0346, predicted to encode a protein that confers antibiotic resistance, has been frequently exchanged among lineages and thus may contribute to pathogen fitness. Finally, we found that isolates from diseased crops and from components of the water cycle, collected during the same crop disease epidemic, form a single population. This provides the strongest evidence yet that precipitation and irrigation water are an overlooked inoculum source for disease epidemics caused by P. syringae.
Landscape of X chromosome inactivation across human tissues
Authors: Tukiainen Taru , Villani Alexandra-Chloé , Yen Angela , Rivas Manuel A. , Marshall Jamie L. , Satija Rahul , Aguirre Matt , Gauthier Laura , Fleharty Mark , Kirby Andrew , Cummings Beryl B. , Castel Stephane E. , Karczewski Konrad J. , Aguet François , Byrnes Andrea ,   Consortium GTEx, Lappalainen Tuuli , Regev Aviv , Ardlie Kristin G. , Hacohen Nir , MacArthur Daniel G.
Published: September 2016

X chromosome inactivation (XCI) silences the transcription from one of the two X chromosomes in mammalian female cells to balance expression dosage between XX females and XY males. XCI is, however, characteristically incomplete in humans: up to one third of X-chromosomal genes are expressed from both the active and inactive X chromosomes (Xa and Xi, respectively) in female cells, with the degree of “escape” from inactivation varying between genes and individuals1,2 (Fig. 1). However, the extent to which XCI is shared between cells and tissues remains poorly characterized3,4, as does the degree to which incomplete XCI manifests as detectable sex differences in gene expression5 and phenotypic traits6. Here we report a systematic survey of XCI using a combination of over 5,500 transcriptomes from 449 individuals spanning 29 tissues, and 940 single-cell transcriptomes, integrated with genomic sequence data (Fig. 1). By combining information across these data types we show that XCI at the 683 X-chromosomal genes assessed is generally uniform across human tissues, but identify examples of heterogeneity between tissues, individuals and cells. We show that incomplete XCI affects at least 23% of X-chromosomal genes, identify seven new escape genes supported by multiple lines of evidence, and demonstrate that escape from XCI results in sex biases in gene expression, thus establishing incomplete XCI as a likely mechanism introducing phenotypic diversity6,7. Overall, this updated catalogue of XCI across human tissues informs our understanding of the extent and impact of the incompleteness in the maintenance of XCI.
The FACT complex and cell cycle progression are essential to maintain asymmetric transcription factor partitioning during cell division
Authors: Herrero Eva , Stinus Sonia , Bellows Eleanor , Thorpe Peter H
Published: September 2016

The polarized partitioning of proteins in cells underlies asymmetric cell division, which is an important driver of development and cellular diversity. Like most cells, the budding yeastSaccharomyces cerevisiaedivides asymmetrically to give two distinct daughter cells. This asymmetry mimics that seen in metazoans and the key regulatory proteins are conserved from yeast to human. A well-known example of an asymmetric protein is the transcription factor Ace2, which localizes specifically to the daughter nucleus, where it drives a daughter-specific transcriptional network. We performed a reverse genetic screen to look for regulators of asymmetry based on the Ace2 localization phenotype. We screened a collection of essential genes in order to analyze the effect of core cellular processes in asymmetric cell division. This identified a large number of mutations that are known to affect progression through the cell cycle, suggesting that cell cycle delay is sufficient to disrupt Ace2 asymmetry. To test this model we blocked cells from progressing through mitosis and found that prolonged cell cycle arrest is sufficient to disrupt Ace2 asymmetry after release. We also demonstrate that members of the evolutionary conserved FACT chromatin-remodeling complex are required for both asymmetric and cell cycle-regulated localization of Ace2.
Comparison of African, Asian, and American Zika Viruses in Swiss Webster mice: Virulence, neutralizing antibodies, and serotypes
Authors: Stauft Charles B. , Gorbatsevych Oleksandr , Cello Jeronimo , Wimmer Eckard , Futcher Bruce
Published: September 2016

The sequence of Zika virus has evolved as it has spread out of Africa and into the Americas. It is unclear whether American strains of the virus define a new serotype. Here, we have tested the virulence and immunogenicity of three wild-type ZIKV strains in neonatal Swiss Webster mice. We found that all three ZIKV strains (African MR766, 1947; Asian FSS13025, 2010; and American, PRVABC59, 2015) are capable of killing neonatal mice after intracranial injection. Intraperitoneal injection with these viruses did not kill, but produced neutralizing antibodies as measured by a PRNT50assay. Sera from mice infected with each virus were tested for neutralizing activity against the infecting virus and also the other two viruses by a PRNT50assay. In general, the antibodies induced by each virus were good at neutralizing that virus (the homologous virus), but somewhat poorer at neutralizing the other two viruses (heterologous viruses). Antibodies induced by the African strain MR766 were about 4-fold worse at neutralizing the American strain PRVABC59 than the homologous strain, while antibodies induced by the American strain were about 10-fold worse at neutralizing the African strain than the homologous strain. Because the antibodies are cross-neutralizing at some level, the viruses do not form separate serotypes. Nevertheless, these results raise concern that the immunity conferred by the African virus may protect only relatively poorly against the new American strains. This has implications for the possible spread of the American ZIKV strains to Africa and Southeast Asia, and also for the development of vaccines.
Clinically-weighted transcriptomic signatures for protein kinase inhibitor associated cardiotoxicity
Authors: van Hasselt JGC , Hansen J , Xiong Y , Shim J , Pickard A , Jayaraman G , Hu B , Mahajan M , Gallo J , Sobie EA , Birtwistle MR , Azeloglu EU , Iyengar R
Published: September 2016

Cardiotoxicity (CT) involving diminished cardiac contractility and heart failure is a major adverse event associated with otherwise efficacious protein kinase inhibitors (KIs). Here, we sought to develop clinically-weighted transcriptomic signatures to predict risk of CT and to better understand the biological processes associated with CT risk. We obtained transcriptome-wide response profiles in four human primary cardiomyocyte cell lines that were treated with 22 different KIs using mRNA sequencing with 3’ digital gene expression. The FDA Adverse Event Reporting System was used to derive relative risk scores for four types of CT for different KIs. We used elastic net regression to associate these transcriptomic profiles with KI-associated risk scores for CT subtypes to obtain clinically-weighted transcriptomic signatures, which showed good predictive properties (cross-validation R2>0.87). Our clinically-weighted transcriptomic signatures for KI-associated CT may be of relevance in early drug development for the prediction of KI-associated CT.
N-Acyl Dopamines Induce Apoptosis in PC12 Cell Line via the O-1918-Sensitive non-CB1-non-CB2 Receptor
Authors: Akimov Mikhail G. , Ashba Alina M. , Gretskaya Natalia M. , Bezuglov Vladimir V.
Published: September 2016

Dopamine amides of long chain fatty acids (NADA) are a family of endogenous mammalian lipids with an unknown function; they are anti-proliferative for many cancer cell lines. The aim of this study was to identify the NADA receptor responsible for cell death induction. Using PC12 cells treated with NADA in combination with various receptor blockers, or pre-treated with the known receptor agonists to down-regulate the proposed receptor, NADA were shown to induce apoptosis. This activity was blocked only by the non-CB1-non-CB2 receptor antagonist O-1918, and by the pre-treatment with the agonists of this receptor ethanolamides of palmitic and oleic acids.
Role of tolerance to resource demand – supply mismatch in a model of annual plants
Authors: Droz Michel , Pękalski Andrzej
Published: September 2016

We propose and discuss a simulation model of annual plants competing for a single resource. Plants are characterised by their tolerance to a shortage of it and the maximum number of seeds a plant could produce in a year. Interaction among plants is reduced to blocking a part of the resource by the plant’s nearest neighbours. Spatial and temporal external conditions remain unchanged. We consider two systems - plants of one type (target plants) and a mixture of two types, when the second type differs from the target ones only by the tolerance to a shortage or surplus of the resource. We show how the life cycle of a plant depends on its tolerance, supply of the resource and how it is affected by the presence of the second type of annuals. We demonstrate that coexistence of the two species is possible, and we determine the conditions for it.
Comparison of two descriptions of heterogeneity used in modelling plants dynamics
Authors: Droz Michel , Pękalski Andrzej
Published: September 2016

We analyse the role played by two different approaches of spatial heterogeneity in theoretical models of annual plants dynamics. The first approach is called quasi-continuous gradient in which one type of resource is changing gradually along the gradient line. In the second one, called the patches approach, part of the habitat is covered by patches and the resource has a different value in each patch. We show that when the spatial heterogeneity of the habitat is small, the two approaches yield the same average number of surviving species, even if a small number of patches is used. In a strong heterogeneity it takes many patches to get similar results as in the gradient case. The difference between the gradient and patchy description of the spatial heterogeneity increases with the number of species present in the system. We have also shown that even when the average number of surviving species is the same, the abundances of species are ordered in a different way, like different species are the dominant ones. The conclusion of this paper is that modelling spatial heterogeneity in a system of plants is not a simple task. Special care is needed when the heterogeneity of the habitat is large, since then depending of the choice of a method, some predictions may differ significantly, making the model non-robust. Therefore the type of theoretical approach must closely match the modelled ecosystem.
Ripping RNA by Force using Gaussian Network Models
Authors: Hyeon Changbong , Thirumalai D.
Published: September 2016

Using force as a probe to map the folding landscapes of RNA molecules has become a reality thanks to major advances in single molecule pulling experiments. Although the unfolding pathways under tension are complicated to predict studies in the context of proteins have shown that topology plays is the major determinant of the unfolding landscapes. By building on this finding we study the responses of RNA molecules to force by adapting Gaussian network model (GNM) that represents RNAs using a bead-spring network with isotropic interactions. Cross-correlation matrices of residue fluctuations, which are analytically calculated using GNM even upon application of mechanical force, show distinct allosteric communication as RNAs rupture. The model is used to calculate the force-extension curves at full thermodynamic equilibrium, and the corresponding unfolding pathways of four RNA molecules subject to a quasi-statically increased force. Our study finds that the analysis using GNM captures qualitatively the unfolding pathway ofT. ribozyme elucidated by the optical tweezers measurement. However, the simple model is not sufficient to capture subtle features, such as bifurcation in the unfolding pathways or the ion effects, in the forced-unfolding of RNAs.
Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer
Authors: Dhawan Andrew , Nichol Daniel , Kinose Fumi , Abazeed Mohamed E. , Marusyk Andriy , Haura Eric B. , Scott Jacob G.
Published: September 2016

Drug resistance remains an elusive problem in cancer therapy, particularly with novel targeted therapy approaches. Much work is currently focused upon the development of an increasing arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops as therapies are continued over time. The current clinical paradigm after failure of first line ALK TKI is to administer another drug in the same class. As to which drug however, the answer is uncertain, as clinical evidence is lacking. To address this shortcoming, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK tyrosine kinase in-hibitors used in clinic, and performed a collateral sensitivity analysis to each of the other drugs. We found that all of the ALK inhibitor resistant cell lines displayed a significant cross-resistance to all other ALK inhibitors. To test for the stability of the resistance phenotypes, we evaluated the ALK-inhibitor sensitivities after drug holidays of varying length (1, 3, 7, 14, and 21 days). We found the resistance patterns to be stochastic and dynamic, with few conserved patterns. This unpredictability led us to an expanded search for treatment options for resistant cells. In this expansion, we tested a panel of 6 more anti-cancer agents for collateral sensitivity among the resistant cells, uncovering a multitude of possibilities for further treatment, including cross-sensitivity to several standard cytotoxic therapies as well as the HSP-90 inhibitors. Taken together, these results imply that resistance to targeted therapy in non-small cell lung cancer is truly a moving target; but also one where there are many opportunities to re-establish sensitivities where there was once resistance.
Multiple factors influence population sex ratios in the Mojave Desert mossSyntrichia caninervis
Authors: Baughman Jenna T. , Payton Adam C. , Paasch Amber E. , Fisher Kirsten M. , McDaniel Stuart F.
Published: September 2016

Premise of research:Natural populations of many mosses appear highly female-biased based on the presence of reproductive structures. This bias could be caused by increased male mortality, lower male growth rate, or a higher threshold for achieving sexual maturity in males. Here we test these hypotheses using samples from two populations of the Mojave Desert mossSyntrichia caninervis.

Methods:We used double digest restriction-site associated DNA (RAD) sequencing to identify candidate sex-associated loci in a panel of sex-expressing plants. Next, we used putative sex-associated markers to identify the sex of individuals without sex structures.

Key results:We found an 18:1 phenotypic female: male sex ratio in the higher elevation site (Wrightwood), and no sex expression at the low elevation site (Phelan). In contrast, based on genetic data we found a 2:1 female bias in the Wrightwood site and only females in the Phelan site. The area occupied by male and female genets was indistinguishable.

Conclusions:These data suggest that both differential mortality and sexual dimorphism in thresholds for sex expression likely contribute to population genetic and phenotypic sex ratio biases, and that phenotypic sex expression alone fails to capture the extent of actual sex ratio bias present in natural populations ofS. caninervis.
GeRelion: GPU-enhanced parallel implementation of single particle cryo-EM image processing
Authors: Su Huayou , Wen Wen , Du Xiaoli , Lu Xicheng , Liao Maofu , Li Dongsheng
Published: September 2016

Single particle cryo-EM emerges as a powerful and versatile method to characterize the structure and function of macromolecules, revealing the structural details of critical molecular machinery inside the cells. RELION is a widely used EM image processing software, and most of the recently published single particle cryo-EM structures were generated by using RELION. Due to the massive computational loads and the growing demands for processing much larger cryo-EM data sets, there is a pressing need to speed up image processing. Here we present GeRelion (https://github.com/gpu-pdl¬nudt/GeRelion), an efficient parallel implementation of RELION on GPU system. In the performance tests using two cryo-EM data sets, GeRelion on 4 or 8 GPU cards outperformed RELION on 256 CPU cores, demonstrating dramatically improved speed and superb scalability. By greatly accelerating single particle cryo-EM structural analysis, GeRelion will facilitate both high resolution structure determination and dissection of mixed conformations of dynamic molecular machines.
Determinants and patterns of the endangered brown bearUrsus arctoshabitat use in the French Pyrenees revealed by occupancy modeling
Authors: Piédallu Blaise , Quenette Pierre-Yves , Bombillon Nicolas , Gastineau Adrienne , Miquel Christian , Gimenez Olivier
Published: September 2016

The Pyrenean brown bear (Ursus arctos) in the mountainous border between France and Spain is one of the smallest and most endangered populations of large carnivores in Europe. Here, we aimed at assessing trends in brown bear habitat use in the Pyrenees and determining the underlying environmental and anthropogenic drivers. Using detection/non-detection data collected between 2008 and 2014 through non-invasive methods, we developed occupancy models to investigate the dynamic of brown bear habitat use in the Pyrenees accounting for local colonization and extinction processes. First, we found two non-connected occupancy cores, one located in the West and another in the Center of the Pyrenees, with an overall significant decrease in habitat use between 2008 and 2014. Second, we showed a negative correlation between human density and bear occupancy in agreement with previous studies on brown bear habitat suitability. Our results confirm the critically endangered status of the Pyrenean population of brown bears.
Massive influence of DNA isolation and library preparation approaches on palaeogenomic sequencing data
Authors: Barlow Axel , Fortes Gloria G. , Dalén Love , Pinhasi Ron , Gasparyan Boris , Rabeder Gernot , Frischauf Christine , Paijmans Johanna L.A. , Hofreiter Michael
Published: September 2016

The ability to access genomic information from ancient samples has provided many important biological insights. Generating such palaeogenomic data requires specialised methodologies, and a variety of procedures for all stages of sample preparation have been proposed. However, the specific effects and biases introduced by alternative laboratory procedures is insufficiently understood. Here, we investigate the effects of three DNA isolation and two library preparation protocols on palaeogenomic data obtained from four Pleistocene subfossil bones. We find that alternative methodologies can significantly and substantially affect total DNA yield, the mean length and length distribution of recovered fragments, nucleotide composition, and the total amount of usable data generated. Furthermore, we also detect significant interaction effects between these stages of sample preparation on many of these factors. Effects and biases introduced in the laboratory can be sufficient to confound estimates of DNA degradation, sample authenticity and genomic GC content, and likely also estimates of genetic diversity and population structure. Future palaeogenomic studies need to carefully consider the effects of laboratory procedures during both experimental design and data analysis, particularly when studies involve multiple datasets generated using a mixture of methodologies.
Cortical dynamics of saccade-target selection during free-viewing of natural scenes
Authors: Henriksson Linda , Ölander Kaisu , Hari Riitta
Published: September 2016

Natural visual behaviour entails explorative eye movements, saccades, that bring different parts of a visual scene into the central vision. The neural processes guiding the selection of saccade targets are still largely unknown. Therefore, in this study, we tracked with magnetoencephalography (MEG) cortical dynamics of viewers who were freely exploring novel natural scenes. Overall, the viewers were largely consistent in their gaze behaviour, especially if the scene contained any persons. We took a fresh approach to relate the eye-gaze data to the MEG signals by characterizing dynamic cortical representations by means of representational distance matrices. Specifically, we compared the representational distances between the stimuli in the evoked MEG responses with predictions based (1) on the low-level visual similarity of the stimuli (as visually more similar stimuli evoke more similar responses in early visual areas) and (2) on the eye-gaze data. At 50–75 ms after the scene onset, the similarity of the occipital MEG patterns correlated with the low-level visual similarity of the scenes, and already at 75–100 ms the visual features attracting the first saccades predicted the similarity of the right parieto-occipital MEG responses. Thereafter, at 100–125 ms, the landing positions of the upcoming saccades explained MEG responses. These results indicate that MEG signals contain signatures of the rapid processing of natural visual scenes as well as of the initiation of the first saccades, with the processing of the saccade target preceding the processing of the landing position of the upcoming saccade.

SIGNIFICANCE STATEMENT

Humans naturally make eye movements to bring different parts of a visual scene to the fovea where our visual acuity is the best. Tracking of eye gaze can reveal how we make inferences about the content of a scene by looking at different objects, or which visual cues automatically attract our attention and gaze. The brain dynamics governing natural gaze behaviour is still largely unknown. Here we suggest a novel approach to relate eye-tracking results with brain activity, as measured with magnetoencephalography (MEG), and demonstrate signatures of natural gaze behaviour in the MEG data already before the eye movements occur.
Investigating the potential of opportunistic sighting data to inform wildlife conservation strategies
Authors: Tenan Simone , Pedrini Paolo , Bragalanti Natalia , Groff Claudio , Sutherland Chris
Published: September 2016

Abundance and space use are key population-level parameters used to inform management and conservation decisions of rare and elusive species, for which monitoring resources can be limited, potentially affecting quality of model-based inference. Recently-developed methods that integrate multiple data sources arising from the same ecological process have typically been focused on data from well-defined sampling protocols, i.e. structured data sets. Despite a rapid increase in availability of large datasets, the value of unstructured or opportunistic data to improve inference about spatial ecological processes is, however, unclear. Using spatial capture-recapture (SCR) methods, we jointly analyze opportunistic recovery of biological samples, traditional SCR data resulting from systematic sampling of hair traps and rub trees, and satellite telemetry data, collected on a reintroduced brown bear population in the central Alps. We compared the precision of sex-specific estimates of density and space use derived from models using combinations of data sources ranging from traditional SCR to a fully integrated SCR model that includes both telemetry and opportunistic data. Estimates of density and space use were more precise when unstructured data were added compared to estimates from a classical SCR model. Our results demonstrate that citizen science data lend itself naturally to integration with in the SCR framework and highlight the value of opportunistic data for improving inference about space use, and in turn, of abundance and density. When individual identity and location can be obtained from opportunistic observations, such data are informative about space use and thus have the potential to improve estimates of movement and density using SCR methods. This is particularly relevant in studies of rare or elusive species, where the amount of SCR encounters is usually small, but also budget restrictions and the difficulty of collaring animals limit the number of individuals for which telemetry information is available. Spatially-referenced opportunistic data thus potentially increase both the geographic extent of a study and the number of individuals with available spatial information, providing an improved understanding of how individuals are distributed and how they use space – fundamental components for calibrating conservation management actions.
Genome‑wide identification and characterization of Transcription Factors of Basic Leucine Zipper Family inMalus domestica
Authors: Zhang Zhengrong , Cui Haoran , Xing Shanshan , Liu Xin , Chen Xuesen , Wang Xiaoyun
Published: September 2016

Basic leucine zipper proteins (bZIP) contain a basic DNA-binding region and a leucine zipper region, acting as transcriptional factors in regulation of gene expression exclusively in eukaryotes. In this investigation, total 116 bZIP members were identified in apple genome and mapped on all 17 chromosomes with various densities asM.bZIPs. All these members were divided into six groups according to the phylogenetic relationship combining with bZIPs from rice andArabidopsis. Investigating gene structure ofM.bZIPs, five splicing patterns of intron were found in the DNA-binging region with no splicing position and splicing positions at different nucleotide of codons or different positions. Analyzing of protein structure ofM.bZIPs, twenty-five motifs were identified with certain characteristic in different phylogenetic groups. To predict dimerization of leucine zipper region, the key positions of amino acid in heptad(s) were investigated. The results showed that mostM.bZIPs may form hetero-dimer or homo-dimer and someM.bZIPs may form both. Expression experiment revealed thatM.bZIP genes have organ-specific expression and widely expressed in flowers, leaves, and fruits. To investigate the response ofM.bZIPs to abiotic stresses, the promoter sequences of randomly selectedM.bZIP genes were analyzed.Cis-acting elements related to multiple stresses were found existing widely in promoter sequences. Quantitative real-time PCR results further demonstrated that the expression of someM.bZIP genes were quite sensitive to exogenous abscisic acid and osmotic treatments.
Low-frequency cortical oscillations are modulated by temporal prediction and temporal error coding
Authors: Barne Louise Catheryne , Claessens Peter Maurice Erna , Reyes Marcelo Bussotti , Caetano Marcelo Salvador , Cravo André Mascioli
Published: September 2016

Monitoring and updating temporal predictions are critical abilities for adaptive behavior. Here, we investigated whether neural oscillations are related to violation and updating of temporal predictions. Human participants performed an experiment in which they had to generate a target at an expected time point, by pressing a button while taking into account a variable delay between the act and the stimulus occurrence. Our behavioral results showed that participants quickly adapted their temporal predictions in face of an error. Concurrent electrophysiological (EEG) data showed that temporal errors elicited markers that are classically related to error coding. Furthermore, intertrial phase coherence of frontal theta oscillations was modulated by error magnitude, possibly indexing the degree of surprise. Finally, we found that delta phase at stimulus onset was correlated with future behavioral adjustments. Together, our findings suggest that low frequency oscillations play a key role in monitoring and in updating temporal predictions.
Diffusion of lipids and GPI-anchored proteins in actin-free plasma membrane vesicles measured by STED-FCS
Authors: Schneider Falk , Clausen Mathias P , Waithe Dominic , Koller Thomas , Ozhan Gunes , Eggeling Christian , Sezgin Erdinc
Published: September 2016

Diffusion and interaction dynamics of molecules at the plasma membrane play an important role in cellular signalling. These have been suggested to be strongly associated with the actin cytoskeleton. Here, we utilise super-resolution STED microscopy combined with fluorescence correlation spectroscopy (STED-FCS) to access the sub-diffraction diffusion regime of different fluorescent lipid analogues and GPI-anchored proteins (GPI-APs) in the cellular plasma membrane, and compare it to the diffusion regime of these molecules in cell-derived actin-free giant plasma membrane vesicles (GPMVs). We show that phospholipids and sphingomyelin, which undergo hindered diffusion in the live cell membrane, diffuse freely in the GPMVs. In contrast to sphingomyelin, which is transiently trapped on molecular-scale complexes in intact cells, diffusion of the ganglioside lipid GM1 suggests transient incorporation into nanodomains, which is less influenced by the actin cortex. Finally, our data on GPI-APs indicate two molecular pools in living cells, one pool showing high mobility with trapped and compartmentalized diffusion, and the other forming immobile clusters both of which disappear in GPMVs. Our data underlines the crucial role of the actin cortex in maintaining hindered diffusion modes of most but not all membrane molecules.