bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Stewardship in the Neonatal Intensive Care Unit: Effects of an Automatic 48-Hour Antibiotic Stop Order on Antibiotic Use
Authors: Astorga Maria Corazon , Piscitello Kyle J , Menda Nina , Ebert Ann M , Ebert Steven C , Porte Michael A , Kling Pamela J
Published: May 2018

Background

Meeting antibiotic stewardship goals in the neonatal intensive care unit (NICU) is challenging because of the unique nature of newborns and the lack of specificity of clinical signs of sepsis. Antibiotics are commonly continued for 48 hours pending culture results and clinical status. The goal of this study was to examine if the implementation of a 48-hour automatic stop (autostop) order during NICU admissions would decrease antibiotic use at UnityPoint Health–Meriter.

Methods

An observational double-cohort study was performed in a level 3 NICU. Antibiotic use was evaluated before and after the autostop initiative. The admission order set included 48 hours of ampicillin and gentamicin coverage.

Results

After the autostop initiation, total doses given per patient decreased by 35% and doses per patient-day decreased by 25% (P < .0001). The greatest effect was a 66% decrease in the use of vancomycin, an antibiotic not included in the admission order set. Providers proactively continued antibiotics for infants in whom they had high suspicion for sepsis and in those with positive blood or cerebral spinal fluid culture results.

Conclusions

An admission-order autostop was highly effective at decreasing antibiotic usage with no doses intended for a pathogen missed. Fewer doses of certain antibiotics outside of the admission order set were administered, particularly vancomycin, which results in our speculation that provider awareness of the antibiotic stewardship initiative might have altered prescribing practices.
Police Liaison Officers at Football: Challenging Orthodoxy through Communication and Engagement
Authors: Hoggett James , West Owen
Published: May 2018

This article expands upon research on the use of Police Liaison Teams (PLTs) within public order policing operations surrounding football fixtures. Using a Participant Action Research approach, the article reports on PLT use across multiple events and locations with different police forces, different personnel and fans and divergent command perspectives, as well as comparative data from PLT and non-PLT events. It identifies how accountability dynamics associated with the classification and management of risk in the policing of football may explain the continued reliance on more coercive policing tactics, as well as a number of other barriers that hinder the development of PLT use at football. Despite this, the article provides evidence that PLTs can offer similar benefits to the policing of football as they do to the policing of protest. In particular, we argue that developing such approaches will make the policing of football more human-rights complaint.
High Maternal Body Mass Index Is Associated with an Early-Onset of Overweight/Obesity in Pre-School-Aged Children in Malawi. A Multilevel Analysis of the 2015-16 Malawi Demographic and Health Survey
Authors: Ntenda Peter Austin Morton , Mhone Thomas Gabriel , Nkoka Owen
Published: May 2018

Background

Overweight/obesity in young children is one of the most serious public health issues globally. We examined whether individual- and community-level maternal nutritional status is associated with an early onset of overweight/obesity in pre-school-aged children in Malawi.

Design

Data were obtained from the 2015-16 Malawi Demographic and Health Survey (MDHS). The maternal nutritional status as body mass index and childhood overweight/obesity status was assessed by using the World Health Organization (WHO) recommendations. To examine whether the maternal nutritional status is associated with overweight/obesity in pre-school-aged children, two-level multilevel logistic regression models were constructed on 4023 children of age less than five years dwelling in 850 different communities.

Results

The multilevel regression analysis showed that children born to overweight/obese mothers had increased odds of being overweight/obese [adjusted odds ratio (aOR) = 3.11; 95% confidence interval (CI): 1.13–8.54]. At the community level, children born to mothers from the middle (aOR: 1.68; 95% CI: 1.02–2.78) and high (aOR: 1.69; 95% CI: 1.00–2.90) percentage of overweight/obese women had increased odds of being overweight/obese. In addition, there were significant variations in the odds of childhood overweight/obesity in the communities.

Conclusions

Strategies aimed at reducing childhood overweight/obesity in Malawi should address not only women and their children but also their communities. Appropriate choices of nutrition, diet and physical activity patterns should be emphasized upon in overweight/obese women of childbearing age throughout pregnancy and beyond.
Warming under seminatural outdoor conditions in the larval stage negatively affects insect flight performance
Authors: Tüzün Nedim , Op de Beeck Lin , Oliarinony Ranalison , Van Dievel Marie , Stoks Robby
Published: May 2018

Laboratory studies indicate global warming may cause changes in locomotor performance directly relevant for fitness and dispersal. Yet, this remains to be tested under seminatural settings, and the connection with warming-induced alterations in the underlying traits has been rarely studied. In an outdoor mesocosm experiment with the damselflyIschnura elegans, 4°C warming in the larval stage decreased the flight muscle mass, which correlated with a lower flight endurance. Warming did not affect body mass, size or wing morphology. This illustrates how carry-over effects of warming under seminatural conditions during early development bridge metamorphosis and negatively impact locomotor performance through changes in a key flight-related trait.
A tropical arthropod unravels local and global environmental dependence of seasonal temperature–size response
Authors: Pequeno Pedro Aurélio Costa Lima , Franklin Elizabeth , Norton Roy A. , de Morais José W.
Published: May 2018

In most ectotherms, adult body size decreases with warming, the so-called ‘temperature–size rule' (TSR). However, the extent to which the strength of the TSR varies naturally within species is little known, and the significance of this phenomenon for tropical biota has been largely neglected. Here, we show that the adult body mass of the soil mite
Rostrozetes ovulum
declined as maximum temperature increased over seasons in a central Amazonian rainforest. Further, per cent decline per °C was fourfold higher in riparian than in upland forests, possibly reflecting differences in oxygen and/or resource supply. Adding our results to a global dataset revealed that, across terrestrial arthropods, the seasonal TSR is generally stronger in hotter environments. Our study suggests that size thermal dependence varies predictably with the environment both locally and globally.
Playing ‘hide-and-seek’ with factor H: game-theoretical analysis of a single nucleotide polymorphism
Authors: Hummert Sabine , Glock Christina , Lang Stefan N. , Hummert Christian , Skerka Christine , Zipfel Peter F. , Germerodt Sebastian , Schuster Stefan
Published: May 2018

As a part of the complement system, factor H regulates phagocytosis and helps differentiate between a body's own and foreign cells. Owing to mimicry efforts, some pathogenic microorganisms such as
Candida albicans
are able to bind factor H on their cell surfaces and, thus, become similar to host cells. This implies that the decision between self and foreign is not clear-cut, which leads to a classification problem for the immune system. Here, two different alleles determining the binding affinity of factor H are relevant. Those alleles differ in the SNP Y402H; they are known to be associated with susceptibility to certain diseases. Interestingly, the fraction of both alleles differs in ethnic groups. The game-theoretical model proposed in this article explains the coexistence of both alleles by a
battle of the sexes
game and investigates the trade-off between pathogen detection and protection of host cells. Further, we discuss the ethnicity-dependent frequencies of the alleles. Moreover, the model elucidates the mimicry efforts by pathogenic microorganisms.
Flow rate of transport network controls uniform metabolite supply to tissue
Authors: Meigel Felix J. , Alim Karen
Published: May 2018

Life and functioning of higher organisms depends on the continuous supply of metabolites to tissues and organs. What are the requirements on the transport network pervading a tissue to provide a uniform supply of nutrients, minerals or hormones? To theoretically answer this question, we present an analytical scaling argument and numerical simulations on how flow dynamics and network architecture control active spread and uniform supply of metabolites by studying the example of xylem vessels in plants. We identify the fluid inflow rate as the key factor for uniform supply. While at low inflow rates metabolites are already exhausted close to flow inlets, too high inflow flushes metabolites through the network and deprives tissue close to inlets of supply. In between these two regimes, there exists an optimal inflow rate that yields a uniform supply of metabolites. We determine this optimal inflow analytically in quantitative agreement with numerical results. Optimizing network architecture by reducing the supply variance over all network tubes, we identify patterns of tube dilation or contraction that compensate sub-optimal supply for the case of too low or too high inflow rate.
Effects of biochar on the fate and toxicity of herbicide fenoxaprop-ethyl in soil
Authors: Jing Xu , Wang Tengfei , Yang Jiali , Wang Yanli , Xu Huifang
Published: May 2018

Biochar, as a soil amendment in agriculture, has attracted considerable attention. In the study, the fate and toxicity of the herbicide fenoxaprop-ethyl were evaluated in soils with and without 5% rice husk biochar amendment. Fenoxaprop-ethyl and metabolite fenoxaprop degradation followed first-order kinetics in the two soils. Fenoxaprop-ethyl decreased fast with half-lives less than 2 days. Large amounts of fenoxaprop formed and remained in the control soil. However, fenoxaprop was much lower in the biochar-amended soil with reduction over 85% on the 35th day. The estimated half-lives of fenoxaprop were 56.9 and 1.5 days in the control and biochar-amended soils, respectively. Biochar restrained the formation and promoted the dissipation of fenoxaprop. Biological indicator earthworms (Eisenia fetida) were used in a 14-day acute toxicity test. Fenoxaprop-ethyl showed low toxicity to earthworms with LC50value of 322.9 µg g−1. Biochar amendment was non-toxic to earthworms and effectively reduced the toxicity. The results suggested that the application of biochar may reduce the risks of fenoxaprop-ethyl in the soil environment.
Measuring visual search and distraction in immersive virtual reality
Authors: Olk Bettina , Dinu Alina , Zielinski David J. , Kopper Regis
Published: May 2018

An important issue of psychological research is how experiments conducted in the laboratory or theories based on such experiments relate to human performance in daily life. Immersive virtual reality (VR) allows control over stimuli and conditions at increased ecological validity. The goal of the present study was to accomplish a transfer of traditional paradigms that assess attention and distraction to immersive VR. To further increase ecological validity we explored attentional effects with daily objects as stimuli instead of simple letters. Participants searched for a target among distractors on the countertop of a virtual kitchen. Target–distractor discriminability was varied and the displays were accompanied by a peripheral flanker that was congruent or incongruent to the target. Reaction time was slower when target–distractor discriminability was low and when flankers were incongruent. The results were replicated in a second experiment in which stimuli were presented on a computer screen in two dimensions. The study demonstrates the successful translation of traditional paradigms and manipulations into immersive VR and lays a foundation for future research on attention and distraction in VR. Further, we provide an outline for future studies that should use features of VR that are not available in traditional laboratory research.
Aspiration-based coevolution of link weight promotes cooperation in the spatial prisoner's dilemma game
Authors: Shen Chen , Chu Chen , Shi Lei , Perc Matjaž , Wang Zhen
Published: May 2018

In this article, we propose an aspiration-based coevolution of link weight, and explore how this set-up affects the evolution of cooperation in the spatial prisoner's dilemma game. In particular, an individual will increase the weight of its link to its neighbours only if the payoff received via this interaction exceeds a pre-defined aspiration. Conversely, if the received payoff is below this aspiration, the link weight with the corresponding neighbour will decrease. Our results show that an appropriate aspiration level leads to a high-cooperation plateau, whereas too high or too low aspiration will impede the evolution of cooperation. We explain these findings with a comprehensive analysis of transition points and with a systematic analysis of typical configuration patterns. The presented results provide further theoretical insights with regards to the impact of different aspiration levels on cooperation in human societies.
Detecting and harmonizing scanner differences in the ABCD study - annual release 1.0
Authors: Nielson Dylan M. , Pereira Francisco , Zheng Charles Y. , Migineishvili Nino , Lee John A. , Thomas Adam G. , Bandettini Peter A.
Published: May 2018

In order to obtain the sample sizes needed for robustly reproducible effects, it is often necessary to acquire data at multiple sites using different MRI scanners. This poses a challenge for investigators to account for the variance due to scanner, as balanced sampling is often not an option. Similarly, longitudinal studies must deal with known and unknown changes to scanner hardware and software over time. In this manuscript, we have explored scanner-related differences in the dataset recently released by the Adolescent Brain Cognitive Development (ABCD) project, a multi-site, longitudinal study of children age 9-10. We demonstrate that scanner manufacturer, model, as well as the individual scanner itself, are detectable in the resting and task-based fMRI results of the ABCD dataset. We further demonstrate that these differences can be harmonized using an empirical Bayes approach known as ComBat. We argue that accounting for scanner variance, including even minor differences in scanner hardware or software, is crucial for any analysis.
Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia
Authors: Gialluisi Alessandro , Andlauer Till F M , Mirza-Schreiber Nazanin , Moll Kristina , Hoffmann Per , Ludwig Kerstin U , Czamara Darina , Francks Clyde , St Pourcain Beate , Brandler William , Honbolygó Ferenc , Tóth Dénes , Csépe Valéria , Huguet Guillaume , Morris Andrew P , Hulslander Jacqueline , Willcutt Erik G , DeFries John C , Olson Richard K , Smith Shelley D , Pennington Bruce F , Vaessen Anniek , Maurer Urs , Lyytinen Heikki , Peyrard-Janvid Myriam , Leppänen Paavo H T , Brandeis Daniel , Bonte Milene , Stein John F , Talcott Joel B , Fauchereau Fabien , Bourgeron Thomas , Monaco Anthony P , Ramus Franck , Landerl Karin , Kere Juha , Scerri Thomas S , Paracchini Silvia , Fisher Simon E , Schumacher Johannes , Nöthen Markus M , Müller-Myhsok Bertram , Schulte-Körne Gerd
Published: May 2018

Developmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468).

We observed a genome-wide significant effect (p<1×10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 withinMIR924HG (micro-RNA 924 host gene;p= 4.73×10−9), and a suggestive association on 8q12.3 withinNKAIN3(encoding a cation transporter;p= 2.25 ×10−8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported withinCELF4(18q12.2), a gene highly expressed in the fetal brain which is co-expressed withNKAIN3and predicted to be a target ofMIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.
Supporting global biodiversity assessment through high-resolution macroecological modelling: Methodological underpinnings of the BILBI framework
Authors: Hoskins Andrew J , Harwood Thomas D , Ware Chris , Williams Kristen J , Perry Justin J , Ota Noboru , Croft Jim R , Yeates David K , Jetz Walter , Golebiewski Maciej , Purvis Andy , Robertson Tim , Ferrier Simon
Published: May 2018

Aim

Global indicators of change in the state of terrestrial biodiversity are often derived by intersecting observed or projected changes in the distribution of habitat transformation, or of protected areas, with underlying patterns in the distribution of biodiversity. However the two main sources of data used to account for biodiversity patterns in such assessments – i.e. ecoregional boundaries, and vertebrate species ranges – are typically delineated at a much coarser resolution than the spatial grain of key ecological processes shaping both land-use and biological distributions at landscape scale. Species distribution modelling provides one widely used means of refining the resolution of mapped species distributions, but is limited to a subset of species which is biased both taxonomically and geographically, with some regions of the world lacking adequate data to generate reliable models even for better-known biological groups.

Innovation

Macroecological modelling of collective properties of biodiversity (e.g. alpha and beta diversity) as a correlative function of environmental predictors offers an alternative, yet highly complementary, approach to refining the spatial resolution with which patterns in the distribution of biodiversity can be mapped across our planet. Here we introduce a new capability – BILBI (the Biogeographic Infrastructure for Large-scaled Biodiversity Indicators) – which has implemented this approach by integrating advances in macroecological modelling, biodiversity informatics, remote sensing and high-performance computing to assess spatial-temporal change in biodiversity at ~1km grid resolution across the entire terrestrial surface of the planet. The initial implementation of this infrastructure focuses on modelling beta-diversity patterns using a novel extension of generalised dissimilarity modelling (GDM) designed to extract maximum value from sparsely and unevenly distributed occurrence records for over 400,000 species of plants, invertebrates and vertebrates.

Main conclusions

Models generated by BILBI greatly refine the mapping of beta-diversity patterns relative to more traditional biodiversity surrogates such as ecoregions. This capability is already proving of considerable value in informing global biodiversity assessment through: 1) generation of indicators of past-to-present change in biodiversity based on observed changes in habitat condition and protected-area coverage; and 2) projection of potential future change in biodiversity as a consequence of alternative scenarios of global change in drivers and policy options.
Short-term effectiveness of HIV care coordination among persons with recent HIV diagnosis or history of poor HIV outcomes
Authors: Nash Denis , Robertson McKaylee M. , Penrose Kate , Chamberlin Stephanie , Robbins Rebekkah S. , Braunstein Sarah L. , Myers Julie E. , Abraham Bisrat , Kulkarni Sarah , Waldron Levi , Levin Bruce , Irvine Mary K.
Published: May 2018

The New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups (newly diagnosed or previously diagnosed and either consistently unsuppressed, inconsistently suppressed or consistently suppressed). We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15·3% were newly diagnosed; among the 84·7% previously diagnosed, 14·2% were consistently suppressed, 28·9% were inconsistently suppressed, and 41 ·6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59·9% of CCP and 53·9% of non-CCP participants had viral load suppression (Relative Risk=1.11, 95%CI:1.08-1.14). Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09-1.23) and 1.32 (95%CI:1.23-1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance.
Structural basis for transfer RNA mimicry by a bacterial Y RNA
Authors: Wang Wei , Chen Xinguo , Wolin Sandra L. , Xiong Yong
Published: May 2018

Noncoding Y RNAs are present in both animal cells and many bacteria. In all species examined, Y RNAs tether the Ro60 protein to an effector protein to perform various cellular functions. For example, in the bacteriumDeinococcus radiodurans, Y RNA tethers Ro60 to the exoribonuclease polynucleotide phosphorylase, specializing this nuclease for structured RNA degradation. Recently, a new Y RNA subfamily was identified in bacteria. Bioinformatic analyses of these YrlA (Y RNA-like A) RNAs predict that the effector-binding domain resembles tRNA. We present the structure of this domain, the overall folding of which is strikingly similar to canonical tRNAs. The tertiary interactions that are responsible for stabilizing tRNA are present in YrlA, making it a close tRNA mimic. However, YrlA lacks a free CCA end and contains a kink in the stem corresponding to the anticodon stem. Since nucleotides in the D and T stems are conserved among YrlAs, they may be an interaction site for an unknown factor. Our experiments identify YrlA RNAs as a new class of tRNA mimics.
Broom: Application for non-redundant storage of High Throughput Sequencing data
Authors: Albayrak Levent , Khanipov Kamil , Golovko George , Fofanov Yuriy
Published: May 2018

Motivation

The data generation capabilities of High Throughput Sequencing (HTS) instruments have exponentially increased over the last few years, while the cost of sequencing has dramatically decreased allowing this technology to become widely used in biomedical studies. For small labs and individual researchers, however, storage and transfer of large amounts of HTS data present a significant challenge. The recent trends in increased sequencing quality and genome coverage can be used to reconsider HTS data storage strategies.

Results

We present Broom, a stand-alone application designed to select and store only high-quality sequencing reads at extremely high compression rates. Written in C++, the application accepts single and paired-end reads in FASTQ and FASTA formats and decompresses data in FASTA format.

Availability

C++ code available at https://scsb.utmb.edu/labgroups/fofanov/broom.asp

Contact

lealbayr@utmb.edu
Germline genetic variants associated with leukocyte-genes predict tumor recurrence in breast cancer patients
Authors: Milanese Jean-Sébastien , Tibiche Chabane , Zou Jinfeng , Meng Zhi Gang , Nantel Andre , Drouin Simon , Marcotte Richard , Wang Edwin
Published: May 2018

Germline genetic variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5-10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n=755) cancer patients. Gene signatures derived from the genes containing functionally germline genetic variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n=200 and 295, P=1.4×10−3). Furthermore, we found that recurred patients possessed a higher rate of germline genetic variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes (or drug response) in breast cancer, other cancer types and even other complex diseases.
Pollen metabarcoding as a tool for tracking long-distance insect migrations
Authors: Suchan Tomasz , Talavera Gerard , Sáez Llorenç , Ronikier Michał , Vila Roger
Published: May 2018

Insects account for the main fraction of Earth’s biodiversity and are key players for ecosystems, notably as pollinators. While insect migration is suspected to represent a natural phenomenon of major importance, remarkably little is known about it, except for a few flagship species. The reason for this situation is mainly due to technical limitations in the study of insect movement. Here we propose using metabarcoding of pollen carried by insects as a method for tracking their migrations. We developed a flexible and simple protocol allowing high multiplexing and not requiring DNA extraction, one of the most time consuming part of metabarcoding protocols, and apply this method to the study of the longdistance migration of the butterflyVanessa cardui,an emerging model for insect migration. We collected 47 butterfly samples along the Mediterranean coast of Spain in spring and performed metabarcoding of pollen collected from their bodies to test for potential arrivals from the African continent. In total, we detected 157 plant species from 23 orders, most of which (82.8%) were insect-pollinated. African or African-Arabian endemic taxa contributed 21.0% of our dataset, strongly supporting the hypothesis that migratory butterflies colonize southern Europe from Africa in spring. Moreover, our data suggest that a northwards trans-Saharan migration in spring is plausible for early arrivals (February) into Europe, as shown by the presence of Saharan floristic elements. Our results demonstrate the possibility of regular insect-mediated transcontinental pollination, with potential implications for ecosystem functioning, agriculture and plant phylogeography. Despite current limitations, mostly regarding the availability of plant reference sequences and distribution data, the method proved to be useful and demonstrates great potential as plant genetic libraries and distribution datasets improve.
Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution
Authors: Roddie Hannah Grace , Armitage Emma Louise , Johnston Simon Andrew , Evans Iwan Robert
Published: May 2018

Macrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage-apoptotic cell interactions on macrophage behaviour are poorly understood. UsingDrosophilaembryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Simu leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells. Removal of apoptosis ameliorates these phenotypes, while acute induction of apoptosis phenocopies these defects and reveals that phagocytosis of apoptotic cells is not necessary for their anti-inflammatory action. Furthermore, Simu is necessary for clearance of necrotic debris and rentention of macrophages at wounds. Thus, Simu is a general detector of damaged self and represents a novel molecular player in controlling resolution of inflammation.
An image-based assay to quantify changes in proliferation and viability upon drug treatment in 3D microenvironments
Authors: Murali Vasanth S. , Chang Bo-Jui , Fiolka Reto , Danuser Gaudenz , Cobanoglu Murat Can , Welf Erik S.
Published: May 2018

Background

Every biological experiment requires a choice of throughput balanced against physiological relevance. Most primary drugs screens neglect critical parameters such as microenvironmental conditions, cell-cell heterogeneity, and specific readouts of cell fate for the sake of throughput.

Methods

Here we describe a methodology to quantify proliferation and viability of single cells in 3D culture conditions by leveraging automated microscopy and image analysis to facilitate reliable and high-throughput measurements. We detail experimental conditions that can be adjusted to increase either throughput or robustness of the assay, and we provide a stand alone image analysis program for users who wish to implement this 3D drug screening assay in high throughput.

Results

We demonstrate this approach by evaluating a combination of RAF and MEK inhibitors on melanoma cells, showing that cells cultured in 3D collagen-based matrices are more sensitive than cells grown in 2D culture, and that cell proliferation is much more sensitive than cell viability. We also find that cells grown in 3D cultured spheroids exhibit equivalent sensitivity to single cells grown in 3D collagen, suggesting that for the case of melanoma, a 3D single cell model may be equally effective for drug identification as 3D spheroids models. The single cell resolution of this approach enables stratification of heterogeneous populations of cells into differentially responsive subtypes upon drug treatment, which we demonstrate by determining the effect of RAK/MEK inhibition on melanoma cells co-cultured with fibroblasts. Furthermore, we show that spheroids grown from single cells exhibit dramatic heterogeneity to drug response, suggesting that heritable drug resistance can arise stochastically in single cells but be retained by subsequent generations.

Conclusion

In summary, image-based analysis renders cell fate detection robust, sensitive, and high-throughput, enabling cell fate evaluation of single cells in more complex microenvironmental conditions.
Myosin-II activity generates a dynamic steady state with continuous actin turnover in a minimal actin cortex
Authors: Sonal  , Ganzinger Kristina A. , Vogel Sven K. , Mücksch Jonas , Blumhardt Philipp , Schwille Petra
Published: May 2018

Dynamic reorganization of the actomyosin cytoskeleton allows a fine-tuning of cell shape that is vital to many cellular functions. It is well established that myosin-II motors generate the forces required for remodeling the cell surface by imparting contractility to actin networks. An additional, less understood, role of myosin-II in cytoskeletal dynamics is believed to be in the regulation of actin turnover; it has been proposed that myosin activity increases actin turnover in various cellular contexts, presumably by contributing to disassembly. In vitro reconstitution of actomyosin networks has confirmed the role of myosin in actin network disassembly, but factors such as diffusional constraints and the use of stabilized filaments have thus far limited the observation of myosin-assisted actin turnover in these networks. Here, we present the reconstitution of a minimal dynamic actin cortex where actin polymerization is catalyzed on the membrane in the presence of myosin-II activity. We demonstrate that myosin activity leads to disassembly and redistribution in this simplified cortex. Consequently, a new dynamic steady state emerges in which actin filaments undergo constant turnover. Our findings suggest a multi-faceted role of myosin-II in fast remodeling of the eukaryotic actin cortex.
Overcome Competitive Exclusion in Ecosystems
Authors: Wang Xin , Liu Yang-Yu
Published: May 2018

Explaining biodiversity in nature is a fundamental problem in ecology. One great challenge is embodied in the so-called competitive exclusion principle1-4: the number of species in steady coexistence cannot exceed the number of resources4-7. In the past five decades, various mechanisms have been proposed to overcome the limit on diversity set by the competitive exclusion principle8-25. Yet, none of the existing mechanisms can generically overcome competitive exclusion at steady state4,26. Here we show that by forming chasing triplets in the predation process among the consumers and resources, the number of coexisting species of consumers can exceed that of resources at steady state, naturally breaking the competitive exclusion principle. Our model can be broadly applicable to explain the biodiversity of many consumer-resource ecosystems and deepen our understanding of biodiversity in nature.
Genomic and phenotypic divergence unveil microgeographic adaptation in the Amazonian hyperdominant tree Eperua falcata Aubl. (Fabaceae)
Authors: Brousseau Louise , Fine Paul V. A. , Dreyer Erwin , Vendramin Giovanni G. , Scotti Ivan
Published: May 2018

Plant populations can undergo very localized adaptation, allowing widely distributed populations to adapt to divergent habitats in spite of recurrent gene flow. Neotropical trees - whose large and undisturbed populations often span a variety of environmental conditions and local habitats - are particularly good models to study this process. Here, we carried out a genome scan for selection through whole-genome sequencing of pools of populations, sampled according to a replicated sampling design, to evaluate microgeographic adaptation in the hyperdominant Amazonian tree Eperua falcata Aubl. (Fabaceae). A high-coverage genomic resource of ∼250 Mb was assembled de novo and annotated, leading to 32,789 predicted genes. 97,062 bi-allelic SNPs were detected over 25,803 contigs, and a custom Bayesian model was implemented to uncover candidate genomic targets of divergent selection. A set of 290 divergence outlier SNPs was detected at the regional scale (between study sites), while 185 SNPs located in the vicinity of 106 protein-coding genes were detected as replicated outliers between microhabitats within regions. Outlier genomic regions are involved in a variety of physiological processes, including plant responses to stress (e.g., oxidative stress, hypoxia and metal toxicity) and biotic interactions. Together with evidence suggesting microgeographic divergence in functional traits, the discovery of genomic targets of microgeographic adaptation in the Neotropics is consistent with the hypothesis that local adaptation is a key driver of ecological diversification, operating across multiple spatial scales, from large- (i.e. regional) to microgeographic- (i.e. landscape) scales.
Resolving the origins of membrane phospholipid biosynthesis genes using outgroupfree rooting
Authors: Coleman Gareth A. , Pancost Richard D. , Williams Tom A.
Published: May 2018

One of the key differences between Bacteria and Archaea are their canonical membrane phospholipids, which are synthesized by distinct biosynthetic pathways with non-homologous enzymes. This “lipid divide” has important implications for the early evolution of cells and the type of membrane phospholipids present in the last universal common ancestor (LUCA). One of the main challenges in studies of membrane evolution is that the key biosynthetic genes are ancient and their evolutionary histories are poorly resolved. This poses major challenges for traditional rooting methods because the only available outgroups are distantly related. Here, we address this issue by using the best available substitution models for single gene trees, by expanding our analyses to the diversity of uncultivated prokaryotes recently revealed by environmental genomics, and by using two complementary approaches to rooting that do not depend on outgroups. Consistent with some previous analyses, our rooted gene trees support extensive inter-domain horizontal transfer of membrane phospholipid biosynthetic genes, primarily from Archaea to Bacteria. They also suggest that the capacity to make archaeal-type membrane phospholipids was already present in LUCA.
Cis-activation in the Notch signaling pathway
Authors: Nandagopal Nagarajan , Santat Leah A. , Elowitz Michael B.
Published: May 2018

The Notch signaling pathway consists of transmembrane ligands and receptors that can interact both within the same cell (cis) and across cell boundaries (trans). Previous work has shown thatcis-interactions act to inhibit productive signaling. Here, by analyzing Notch activation in single cells while controlling cell density and ligand expression level, we show thatcis-ligands can in fact activate Notch receptors. Thiscis-activation process resemblestrans-activation in its ligand level dependence, susceptibility tocis-inhibition, and sensitivity to Fringe modification. Cis-activation occurred for multiple ligand-receptor pairs, in diverse cell types, and affected survival and differentiation in neural stem cells. Finally, mathematical modeling shows howcis-activation could potentially expand the capabilities of Notch signaling, for example enabling “negative” signaling. These results establishcis-activation as a prevalent mode of signaling in the Notch pathway, and should contribute to a more complete understanding of how Notch signaling functions in developmental, physiological, and biomedical contexts.
Safety climate as a relative concept
Authors: Zhang Rita Peihua , Pirzadeh Payam , Lingard Helen , Nevin Steve
Published: May 2018

Purpose

The purpose of this paper is to use a longitudinal approach to measure safety climate at construction projects, and explore the relationship between safety climate and the level of project completion in the dynamic construction project environments.

Design/methodology/approach

Multi-wave safety climate surveys were conducted at four processing plant construction projects in New Zealand. Safety climate was measured with a multi-level measurement instrument, which measured construction workers’ perceptions of client’s organisational safety response (COSR), principal contractor’s organisational safety response (PCOSR), supervisors’ safety response (SSR) and co-workers’ safety response (CWSR).

Findings

At the organisational level, the research identifies a general downward change trend in workers’ perceptions of COSR and PCOSR. At the group level, no clear or consistent change trend is identified between the level of project completion and workers’ perceptions of SSR and CWSR.

Research limitations/implications

The research suggests that the construction project management should consistently emphasise the importance of safety, even when they are facing production pressure. The research highlights the opportunity to examine the role of supervisors’ leadership as an antecedent to the group-level safety climate and the development of workers’ safety concerns for their co-workers over time.

Originality/value

This research provides the starting point for understanding safety climate in the dynamic and constantly changing construction project environments, in which the relative priorities change, adverse events arise and production pressures fluctuate over time.
Labor crew workspace analysis for prefabricated assemblies’ installation
Authors: Wang Qiankun , Guo Zeng , Mei Tingting , Li Qianyao , Li Peng
Published: May 2018

Purpose

Construction industrialization is emerging in the construction industry, as a result, buildings with prefabricated assemblies are gaining more and more ground. In most situations, the prefabricated building assemblies are installed by labor crews manually. If some assemblies are ill-designed, clashes between labor crews’ workspaces and them may occur, which will have bad effect on workers’ productivity and even incur hazard. The purpose of this paper is to provide a 4D building information modeling (BIM) based approach to find potential workspace conflicts during the installation process of prefabricated building assemblies in the detailed design process so as to eliminate them in advance.

Design/methodology/approach

First, a workspace modeling method is provided; second, three kinds of workspace conflicts are analyzed; third, a 4D-BIM-based approach is established; fourth, a prototype tool based on the approach is developed; and finally, a case study is conducted to test the tool.

Findings

The result shows that the proposed tool can detect or precaution workspace conflicts and visualize them in a series of views; in doing so, valuable information can be obtained for improving the design quality of prefabricated assemblies.

Research limitations/implications

The proposed approach and tool only concern the congestions caused by ill-designed prefabricated components; the tool needed to be further optimized for speed; the tests on the tool are limited to a single case study; and more tests are needed to verify its effectiveness.

Originality/value

This research provides a 4D-BIM-based approach and a prototype tool for installation workspace analysis. It can be used to provide support for design optimization of prefabricated building assemblies.
Construction tender price estimation standardization (TPES) in Malaysia
Authors: Hassim Salihudin , Muniandy Ratnasamy , Alias Aidi Hizami , Abdullah Pedram
Published: May 2018

Purpose

The pre-tender estimation process is still a hazy and inaccurate process, despite it has been practiced over decades, especially in Malaysia. The methods evolved over time largely depend on the amount of information available at the time of estimation. More often than not, the estimate produced during the pre-tender stage is far more than the tender cost of the project and sometimes, it is perilously underestimated and caused major problems to the client in the monetary planning. The purpose of this paper is to determine the most influential factors on the deviation of pre-tender cost estimation in Malaysia by conducting a survey.

Design/methodology/approach

Fuzzy logic, combined with artificial neural network method (fuzzy neural network) was then used to develop an estimating model to aid the pre-tender estimation process.

Findings

The results showed that the model is able to shift the cost estimation toward accuracy. This model can be used to improve the pre-tender estimation accuracy, enabling the client to take the necessary early measures in preparing the funding for a building project in Malaysia.

Originality/value

To the authors’ knowledge, this is the first study on tender price estimation standardization for a construction project in Malaysia. In addition, the authors have used factors from literature for the model, which shows the thoroughness of the developed model. Thus, the findings and the model developed in this study should be able to assist contractors in coming out with a more accurate tender price estimation.
The challenges and opportunities of ICT in WIL
Authors: Gerhardt Trevor , Mackenzie-Philps Linda
Published: May 2018

Purpose

Programmes and courses integrating learning and work, captured generally in this paper as work integrated learning (WIL), usually provide flexible and innovative learning opportunities. In a digital age, information and communication technologies (ICTs) can be vital in delivering and enhancing such hybrid forms of WIL. The purpose of this paper is to explore the correlation and trajectory of ICT use among priests in the Church of England in the various forms of WIL.

Design/methodology/approach

The case study explores ICT use among a sample of Church of England priests by examining initially their use of virtual learning environments (VLEs) such as Blackboard and Moodle in work-based learning (WBL); and assessing the trajectory and correlation to work-related learning (WRL) through their use of social networking/engagement tools such as Facebook and Twitter in continuing professional development courses (CPD). The correlation and trajectory is provided through a document analysis of VLE access and a survey questionnaire.

Findings

Priests in WBL and priests engaged in WRL (i.e. CPD courses) revealed a correlation in the lack of ICT pervasiveness. With only a minority of priests engaging in further higher education (HE), the familiarity and use of ICT such as VLE platforms stagnated or declined. Correlated with social networking/engagement, priests overwhelmingly cited the “lack of time” as a reason not to engage with social media, however, ICT reluctance caused by fear was the trajectory resulting in a further lack of “ICT pervasiveness”.

Research limitations/implications

While results may be generalisable among Church of England priests and other faith communities internationally, due to its unique and distinctive parameters, it is not generalisable to the general mature student adult education population.

Practical implications

The case study highlighted that continued intentional familiarisation and use of ICT within the various forms of WIL programmes and courses among “non-digital natives” would enhance learning. Such learning in WIL would be beneficial for HE programmes addressing e-readiness as a priority.

Social implications

Specific to the sample case study, considering the importance of community engagement and WIL, this study highlights the challenges and changes required for improved social capital within the field of ICT and adult education.

Originality/value

No studies have considered the training and education of priests as a WIL case study of ICT “pervasiveness” and self-efficacy.