bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the ICRP 67 and NCRP 156 Biokinetic Models to 241 Am Wound Data from Nonhuman Primates
Authors: Alomairy Nada A. , Brey Richard R. , Guilmette Raymond A.
Published: January 2018

Distribution, retention, and excretion of intramuscularly injected 241Am citrate have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay and retention data, obtained from experiments done by Patricia Durbin and her colleagues at Lawrence Berkeley National Laboratory, were evaluated against the International Commission on Radiological Protection (ICRP 67) 241Am systemic model coupled with to the National Council on Radiation Protection and Measurement wound model (NCRP 156). The default transfer rates suggested in these models were used with the urine and feces excretion data to predict the intake as well as liver and skeleton tissue contents at the time of death. The default models adequately predict the animals’ urine bioassay data, but the injected activities were overpredicted by as much 4.41 times and underpredicted by as much as 0.99 times. Poor prediction has been observed in all cases using fecal excretion. The retained activity in the liver and skeleton were investigated using the same approach. It appears that the models predict the amount of the activity retention in the skeleton more accurately than in the liver. The fraction of predicted to measured activity at the time of death in the skeleton was over 1.0 in most cases, and accurate predictions were obtained in seven cases. The predicted activity in skeleton for these cases ranged from 2.7 to 17% overestimated activity and from 9 to 14% underestimated activity. NHPs’ urine data and organ retention were compared with data from previously modeled baboons and beagle dogs. About 6% of the injected activity in baboons and beagle dog was excreted in urine and approximately 0.1% in feces in the first 24 h. The results from NHP are not different from excreta analysis in these other species. Urinary excretion in the cynomolgus, rhesus, and baboon NHP is the dominant pathway of 241Am clearance; however, fecal excretion is considered dominant in beagle dogs. The comparison between NHPs and humans is difficult due to the differences in the number of activities translocated or deposited in the liver tissue and nonliver tissues (primarily skeleton), in addition to the physiological differences between the NHPs and humans.
Deterministic Effects to the Lens of the Eye Following Ionizing Radiation Exposure
Authors: Thome Christopher , Chambers Douglas B. , Hooker Antony M. , Thompson Jeroen W. , Boreham Douglas R.
Published: January 2018

Ionizing radiation exposure to the lens of the eye is a known cause of cataractogenesis. Historically, it was believed that the acute threshold dose for cataract formation was 5 Sv, and annual dose limits to the lens were set at 150 mSv. Recently, however, the International Commission on Radiological Protection has reduced their threshold dose estimate for deterministic effects to 0.5 Gy and is now recommending an occupational limit of 20 mSv per year on average. A number of organizations have questioned whether this new threshold and dose limit are justified based on the limited reliable data concerning radiation-induced cataracts. This review summarizes all of the published human epidemiological data on ionizing radiation exposure to the lens of the eye in order to evaluate the proposed threshold. Data from a variety of exposure cohorts are reviewed, including atomic bomb survivors, Chernobyl liquidators, medical workers, and radiotherapy patients. Overall, there is not conclusive evidence that the threshold dose for cataract formation should be reduced to 0.5 Gy. Many of the studies reviewed here are challenging to incorporate into an overall risk model due to inconsistencies with dosimetry, sample size, and scoring metrics. Additionally, risk levels in the studied cohorts may not relate to occupational scenarios due to differences in dose rate, radiation quality, age at exposure and latency period. New studies should be designed specifically focused on occupational exposures, with reliable dosimetry and grading methods for lens opacities, to determine an appropriate level for dose threshold and exposure limit.
Silicone Hydrogel and Rigid Gas-Permeable Scleral Lens Tear Exchange
Authors: Paugh Jerry R. , Chen Elaine , Heinrich Colton , Miller Heidi , Gates Tiffany , Nguyen Andrew Loc , Edrington Timothy , Weissman Barry A.
Published: January 2018

Objectives:

To quantify tear elimination rate (ER) underneath silicone hydrogel (Si-Hy) and scleral gas permeable (GP) contact lenses (CLs).

Methods:

Subjects successfully using either well-fitting soft Si-Hy CLs or scleral GP CLs were recruited. Most scleral GP CL wearers had irregular corneas (e.g., keratoconus). An objective fluorometer measured decay of fluorescein isothiocyanate dextran dye signal (70 kD MW) from which the tear ER in %/min was calculated. For GP scleral lenses, the ER was determined for both the initial settling period and the 30- to 60-min period, and without lenses. All ERs were calculated from 5 to 30 min to avoid reflex tearing effects.

Results:

Fourteen soft Si-Hy CL and 12 scleral GP CL wearers completed the study. The ER for the scleral GP CL wearers averaged 0.57 (±0.6) %/min for the 0- to 30-min and 0.42 (±0.5) %/min for the 30- to 60-min period (P=0.515). Non-CL wear tear ER in these same subjects averaged 34.17 (±15.9) %/min and was significantly different versus both scleral GP wear periods (both P values <0.001). The ER for the soft Si-Hy CL wearers, 5 to 30 min, averaged 6.09 (±2.8) %/min.

Conclusions:

Our data demonstrate significantly less ER in well-fit scleral GP CL wearers compared with soft Si-Hy CL wearers for both the settling and longer wear periods (both P values <0.001). Moreover, slightly greater tear exchange was observed during the scleral GP CL settling period than later, which may reflect a change over time in tear vault thickness.
Consequences of Preservative Uptake and Release by Contact Lenses
Authors: Morris Carol A. , Maltseva Inna A. , Rogers Victoria A. , Ni Jing , Khong Kathleen T. , Derringer Charles B. , George Melanie D. , Luk Andrew S.
Published: January 2018

Objectives:

To assess contact lens preservative uptake and release from multipurpose solutions (MPS) and subsequent acquisition of lens antibacterial activity.

Methods:

Kinetics of uptake and release of poly (hexamethylene biguanide hydrochloride) (PHMB) or polyquaternium-1 (PQ-1) from various contact lenses were studied initially with the pure compounds and then after soaking in MPS containing these compounds. Lenses soaked in MPS were tested for antibacterial activity.

Results:

Only lenses with a negatively charged component absorbed these preservatives. For lenses containing methacrylic acid (MA), uptake of PHMB from preservative-only solution was fast, yet little was released, in contrast to its rapid release from lenses containing other anionic groups. This trend persisted with PHMB-containing MPS. PQ-1 from preservative-only solution was only absorbed by lenses containing MA and was released from MA-containing hydrogels, but not significantly from an MA-containing silicone hydrogel. Lens uptake of PQ-1 was much lower from MPS and release was essentially undetectable from all lenses evaluated. Antibacterial lens activity was acquired by lenses containing MA after an overnight soak in MPS containing PQ-1, and for balafilcon A and omafilcon A after 5 exchanges in PHMB-containing MPS. Acquired activity was maintained during cycling between artificial tear protein solution and MPS.

Conclusions:

Lens preservative uptake and its subsequent release are dependent on lens chemistry, preservative nature, and other MPS components. A few lens/solution combinations acquired antibacterial activity after one or more overnight soaks in MPS, depending on the nature of the anionic lens component and the preservative. Uncharged lenses did not acquire antibacterial activity.
Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors
Authors: Yoon Eileen L. , Kim Tae Yeob , Lee Chang Hyeong , Kim Tae Hun , Cho Hyun Chin , Lee Sang Soo , Kim Sung Eun , Kim Hee Yeon , Kim Chang Wook , Song Do Seon , Yang Jin Mo , Sinn Dong Hyun , Jung Young Kul , Yim Hyung Joon , Kim Hyoung Su , Sohn Joo Hyun , Kim Jeong Han , Choe Won Hyeok , Lee Byung Seok , Kim Moon Young , Jeong Soung Won , Choi Eunhee , Kim Dong Joon
Published: January 2018

Goals:

We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF).

Background:

The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known.

Study:

A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition.

Results:

The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode.

Conclusions:

A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.
Free flaps for head and neck cancer in paediatric and neonatal patients
Authors: Elledge Ross , Parmar Satyesh
Published: January 2018

Purpose of review

To review recent literature on the subject of free tissue transfer options in paediatric head and neck surgery, with a particular emphasis on highlighting the advantages and disadvantages of different reconstructions in the paediatric patient.

Recent findings

Free tissue transfer in paediatric patients is predictable and applicable for a wide range of congenital and acquired defects in the head and neck. The free fibula flap is a mainstay of mandibular reconstruction and allows excellent implant-supported prosthodontic rehabilitation and growth potential at the recipient site with little or no donor site morbidity. Other less commonly explored options include the deep circumflex iliac artery flap, scapula flap and medial femoral condyle flap. The gracilis mucle remains the mainstay for facial reanimation with other options including pectoralis minor, rectus abdominis, extensor digitorum brevis and latissimus dorsi. There are compelling arguments for centralization of services and creative strategies in postoperative rehabilitation (e.g. play therapy).

Free flaps in paediatric patients are a viable option and may even have advantages relative to adults because of the absence of atherosclerosis, purported lower risk of vasospasm and proportionally larger vessel size. Transfer earlier in life maximizes functional potential and ‘normalizes’ treatment.
Applications of near infrared spectroscopy in the neonate
Authors: Garvey Aisling A. , Dempsey Eugene M.
Published: January 2018

Purpose of review

There has been a significant increase in the utilization of NIRS in neonatal care over the last few years, with some centers now routinely utilizing this monitoring technique for direct intervention at the bedside. In this review, we provide a summary of the most up-to-date evidence on near infrared spectroscopy utilization, with particular emphasis on measurement of cerebral oxygenation in preterm infants.

Recent findings

There have been significant advances in the technology, leading to an increase in the number of available devices and in the use of this monitoring tool to reduce cerebral injury in preterm infants. The role of NIRS in assessing cerebral autoregulation in preterm and term infants, in evaluating somatic oxygenation, and in the management of newborns with hypoxic ischaemic encephalopathy is discussed.

Two recent pilot randomized controlled trials highlight the potential of cerebral oxygenation monitoring to direct management in the delivery room and the neonatal intensive care unit. However, we urge caution against routine use and await the results of further studies in this area before considering this type of monitoring as standard of care.
Preclinical Data Supporting Antitumor Activity of PD-1 Blockade
Authors: Curran Michael A.
Published: January 2018

Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of both solid and hematologic malignancies in the clinic. These advances were built on a foundation of murine preclinical tumor model studies, which both demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also provided critical insights into the cellular and molecular processes underlying their capacity to elicit immune-mediated tumor regressions. As the field of immunotherapy moves toward higher-order combinations of agents, effective utilization of murine tumor models to optimize the composition of PD-1 antibody combination therapies, as well as their dosing and scheduling, will be essential for effective clinical translation. Novel murine models bearing human tumor xenografts and engrafted human immune systems may help close the gap between preclinical and clinical immunobiology.
Combination Strategies PD-1/PD-L1 Antagonists
Authors: Sznol Mario
Published: January 2018

Despite the broad clinical antitumor activity of PD-1/PD-L1 antagonists, many patients who are treated with these agents either do not respond or achieve suboptimal responses. Improving overall outcome will require combinations with other agents to address potential innate or acquired mechanisms of resistance. Many combination trials have been initiated in patients with or without prior exposure to the PD-1/PD-L1 antagonists. In addition to the challenge of identifying optimal dose, schedule, and sequence for the combinations, current biomarker efforts lack the precision to identify optimal combination partners for the PD-1/PD-L1 antagonists in individual patients. For each possible combination, careful consideration of clinical trial design, biomarker strategies, and endpoints for early clinical development will be necessary to move the most promising regimens forward and therefore to accelerate the rate of clinical progress.
The Influence of Environmental Enrichment on Cardiovascular and Behavioral Responses to Social Stress
Authors: Normann Marigny C. , McNeal Neal , Dagner Ashley , Ihm Elliott , Woodbury Matthew , Grippo Angela J.
Published: January 2018

Objective

Stress is linked to negative cardiovascular consequences and increases in depressive behaviors. Environmental enrichment (EE) involves exposure to novel items that provide physical and cognitive stimulation. EE has behavioral, cognitive, and neurobiological effects that may improve stress responses in humans and animal models. This study investigated the potential protective effects of EE on behavior and cardiovascular function in female prairie voles after a social stressor.

Methods

Radiotelemetry transmitters were implanted into female prairie voles to measure heart rate (HR) and heart rate variability (HRV) throughout the study. All females were paired with a male partner for 5 days, followed by separation from their partner for 5 additional days, and a 10-day treatment period. Treatment consisted of continued isolation, isolation with EE, or re-pairing with the partner (n = 9 per group). After treatment, animals were observed in the forced swim test (FST) for measures of stress coping behaviors.

Results

Isolation elevated HR and reduced HRV relative to baseline for all groups (p < .001). HR and HRV returned to baseline in the EE and re-paired groups, but not in the continued isolation group (p < .001). Animals in the EE and re-paired groups displayed significantly lower immobility time (p < .001) and HR (p < .03) during the FST, with a shorter latency for HR to return to baseline levels after the FST, relative to the continued isolation group (p < .001).

Conclusions

EE and re-pairing reversed the negative behavioral and cardiovascular consequences associated with social isolation.
Vacuum stability in the early universe and the backreaction of classical gravity
Authors: Markkanen Tommi
Published: January 2018

In the case of a metastable electroweak vacuum, the quantum corrected effective potential plays a crucial role in the potential instability of the standard model. In the early universe, in particular during inflation and reheating, this instability can be triggered leading to catastrophic vacuum decay. We discuss how the large space-time curvature of the early universe can be incorporated in the calculation and in many cases significantly modify the flat space prediction. The two key new elements are the unavoidable generation of the non-minimal coupling between the Higgs field and the scalar curvature of gravity and a curvature induced contribution to the running of the constants. For the minimal set up of the standard model and a decoupled inflation sector we show how a metastable vacuum can lead to very tight bounds for the non-minimal coupling. We also discuss a novel and very much related dark matter generation mechanism.

This article is part of the Theo Murphy meeting issue ‘Higgs cosmology’.
Synthetic stimuli reveal a predictive and switch-like activation of the songbird’s vocal motor program
Authors: Bush Alan , Döppler Juan F. , Goller Franz , Mindlin Gabriel B.
Published: January 2018

Acquisition and maintenance of complex vocal behaviors like human speech and oscine birdsong require continuous auditory feedback. The exact way in which this feedback is integrated into the vocal motor programs is not completely understood. Here we show that in sleeping zebra finches (Taeniopygia guttata), the activity of the song system selectively evoked by playbacks of their own song can be detected in the syrinx. Measuring the electrical activity of syringeal muscles, we found playback-evoked patterns identical to those recorded during song execution. Using this global and continuous readout we studied the activation dynamics of the song system elicited by different auditory stimuli. We found that a synthetic version of the bird’s song, rendered by a physical model of the avian phonation apparatus, evoked exactly the same response, albeit with lower efficiency. Analysis of these responses reveal a predictive and switch-like activation of the motor program, with preferred activation instants within the song.

Significance

The study of the integration between sensory inputs and motor commands has greatly benefited from the finding that in sleeping oscine birds, playback of their own song evokes highly specific firing patterns in neurons also involved in the production of that song. Nevertheless, the sparse spiking patterns that can be recorded from few single neurons gives limited information of the overall activity of the song system. Here we show that this response is not limited to the central nervous system, but reaches vocal muscles. Combining this integrated measure of the activity of the system with surrogate synthetic songs, we found an all-or-nothing and predictive activation of the system, suggesting the existence of a pre-programmed internal dynamics.
Anomalous Scaling of Gene Expression in Confined Cell-Free Reactions
Authors: Sakamoto Ryota , Noireaux Vincent , Maeda Yusuke T.
Published: January 2018

Cellular surface breaks the symmetry of molecular diffusion across membrane. Here, we study how steric interactions between the surface and the bulk of cell-sized emulsion droplets alters gene expression emulated by a cell-free transcription/translation (TXTL) system. The concentration of synthesized reporter proteins in droplets of radiusRshows an anomalous geometric scaling ofR4different from the expected normal size-dependence ofR3. Given that TXTL becomes less efficient at thin surface layer, a mathematical model explains anomalous size-dependence found in experiment. The surface of cell-sized compartment thus plays a regulatory role for cell-free gene expression.
Challenging the point neuron dogma: FS basket cells as 2-stage nonlinear integrators
Authors: Tzilivaki Alexandra , Kastellakis George , Poirazi Panayiota
Published: January 2018

Interneurons are critical for the proper functioning of neural circuits. While often morphologically complex, their dendrites have been ignored for decades, treating them as linear point neurons. Exciting new findings reveal complex, non-linear dendritic computations that call for a new theory of interneuron arithmetic. Using detailed biophysical models, we predict that dendrites of FS basket cells in both hippocampus and prefrontal cortex come in two flavors: supralinear, supporting local sodium spikes within large-volume branches and sublinear, in small-volume branches. Synaptic activation of varying sets of these dendrites leads to somatic firing variability that cannot be explained by the point neuron reduction. Instead, a 2-stage Artificial Neural Network (ANN), with sub- and supralinear hidden nodes, captures most of the variance. Reduced neuronal circuit modeling suggest that this bi-modal, 2-stage integration in FS basket cells confers substantial resource savings in memory encoding as well as the linking of memories across time.
The Evolutionary History and Impact of Bacterial tRNA Modifications
Authors: Diwan Gaurav D , Agashe Deepa
Published: January 2018

Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific (“target”) tRNAs to recognize multiple codons and cover for other (“non-target”) tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in non-target tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.
Including phenotypic causal networks in genome-wide association studies using mixed effects structural equation models
Authors: Momen Mehdi , Mehrgardi Ahmad Ayatollahi , Roudbar Mahmoud Amiri , Kranis Andreas , Pinto Renan Mercuri , Valente Bruno D. , Morota Gota , Rosa Guilherme J. M. , Gianola Daniel
Published: January 2018

Background

Phenotypic networks describing putative causal relationships among multiple phenotypes can be used to infer single-nucleotide polymorphism (SNP) effects in genome-wide association studies (GWAS). In GWAS with multiple phenotypes, reconstructing underlying causal structures among traits and SNPs using a single statistical framework is essential for understanding the entirety of genotype-phenotype maps. A structural equation model (SEM) can be used for such purposes.

Methods

We applied SEM to GWAS (SEM-GWAS) in chickens, taking into account putative causal relationships among body weight (BW), breast meat (BM), hen-house production (HHP), and SNPs. We assessed the performance of SEM-GWAS by comparing the model results with those obtained from traditional multi-trait association analyses (MTM-GWAS).

Results

Three different putative causal path diagrams were inferred from highest posterior density (HPD) intervals of 0.75, 0.85, and 0.95 using the inductive causation algorithm. A positive path coefficient was estimated for BM→BW, and negative values were obtained for BM→HHP and BW→HHP in all implemented scenarios. Further, the application of SEM-GWAS enabled the decomposition of SNP effects into direct, indirect, and total effects, identifying whether a SNP effect is acting directly or indirectly on a given trait. In contrast, MTM-GWAS only captured overall genetic effects on traits, which is equivalent to combining the direct and indirect SNP effects from SEMGWAS.

Conclusions

Although MTM-GWAS and SEM-GWAS use the same probabilistic models, we provide evidence that SEM-GWAS captures complex relationships and delivers a more comprehensive understanding of SNP effects compared to MTM-GWAS. Our results showed that SEM-GWAS provides important insight regarding the mechanism by which identified SNPs control traits by partitioning them into direct, indirect, and total SNP effects.
Autometa: Automated extraction of microbial genomes from individual shotgun metagenomes
Authors: Miller Ian J. , Rees Evan R. , Ross Jennifer , Miller Izaak , Baxa Jared , Lopera Juan , Kerby Robert L. , Rey Federico E. , Kwan Jason C.
Published: January 2018

Motivation

Shotgun metagenomics is a powerful, high-resolution technique enabling the study of microbial communitiesin situ.However, species-level resolution is only achieved after a process of “binning” where contigs predicted to originate from the same genome are clustered. Such culture-independent sequencing frequently unearths novel microbes, and so various methods have been devised for reference-free binning. Existing methods, however, suffer from: (1) reliance on human pattern recognition, which is inherently unscalable; (2) requirement for multiple co-assembled metagenomes, which degrades assembly quality due to strain variance; and (3) assumption of prior host genome removal not feasible for non-model hosts. We therefore devised a fully-automated pipeline, termed “Autometa,” to address these issues. Results: Autometa implements a method for taxonomic partitioning of contigs based on predicted protein homology, and this was shown to vastly improve binning in host-associated and complex metagenomes. Autometa’s method of automated clustering, based on Barnes-Hut Stochastic Neighbor Embedding (BH-tSNE) and DBSCAN, was shown to be highly scalable, outperforming other binning pipelines in complex simulated datasets.

Availability and implementation

Autometa is freely available athttps://bitbucket.org/jasonckwan/autometaand as a docker image athttps://hub.docker.com/r/jasonkwan/autometaunder the GNU Affero General Public License 3 (AGPL 3).

Contact

jason.kwan@wisc.edu

Supplementary information

Supplementary data are available attached to this article athttps://biorxiv.org
Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
Authors: Mylonas Constantine , Tessarz Peter
Published: January 2018

The conserved and essential histone chaperone FACT (Facilitates Chromatin Transcription) reorganizes nucleosomes during DNA transcription, replication and repair and ensures both, efficient elongation of RNA Pol II and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of SSRP1 and SUPT16. Here, we show that in contrast to yeast, FACT accumulates at the transcription start site of genes reminiscent of RNA Polymerase II profile. Depletion of FACT in mouse embryonic stem cells leads to up-regulation of pro-proliferative genes and key pluripotency factors concomitant with hyper-proliferation of mES cells. Using MNase-, ATAC-, and Nascent Elongating Transcript Sequencing (NET-seq) we show that up-regulation of genes coincides with loss of nucleosomes upstream of the TSS and concomitant increase in antisense transcription, indicating that FACT impacts the promoter architecture to regulate expression of these genes. Finally, we demonstrate a role for FACT in cell fate determination and show that FACT depletion primes ES cells for the neuronal lineage.
Staphylococcus aureustoxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration
Authors: Haapasalo Karita , Wollman Adam J. M. , Haas Carla de , Kessel Kok van , Strijp Jos van , Leake Mark C.
Published: January 2018

background

Staphylococcus aureusPanton Valentine Leukocidin (PVL) is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored.

Results

Here we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and receptor ‘recycling’ which allows multiple toxin pores to be formed close together. Using live cell single-molecule super-resolution imaging, Förster resonance energy transfer (FRET) and nanoscale total internal reflection fluorescence (TIRF) colocalization microscopy we visualized toxin pore formation in the presence of its natural docking ligand.

Conclusions

We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyper inflammatory reactions in early stages of microbial infections and have implications for several other similar bi-component toxins and the design of new antibiotics.
A Chemogenetic Platform for Spatio-temporal Control of β-arrestin Translocation and Signaling at G protein-Coupled Receptors
Authors: Roth Bryan L , Gotoh Yusuke , Giguere Patrick , Nichols David
Published: January 2018

Although ligand-activated GPCRs induce both G-protein and β-arrestin dependent signaling, gaining precise spatio-temporal control of β-arrestin signaling has proven elusive. Here we describe a platform for specifically activating β-arrestin-dependent signaling in situ. The platform, which we have dubbed GA-PAIR (GPCR/β-Arrestin-Plant protein and Abscisic acid Induced Recruitment), can be controlled by the inert phytochemical S-(+)-abscisic acid (ABA). ABA induces interaction between ABI1 (ABA Insensitive 1) and PYL1 (Pyrabactin Resistance (PYR) 1-Like), two plant proteins with no mammalian counterparts. We fused ABI to the engineered human muscarinic M3 G protein-coupled receptor (hM3Dq) and PYL1 to β-arrestin2. Addition of ABA induced rapid and nearly complete translocation of the PYL-β-arrestin fusion protein and, importantly, induced both ERK and Akt signaling. Photo-uncaging a new photo-caged ABA analogue allowed us to gain relatively precise spatio-temporal control over β-arrestin translocation. Because GA-PAIR facilitates the exclusive activation of endogenous β-arrestin signaling pathways in the absence of a GPCR ligand or G protein, the GA-PAIR system will facilitate deconvoluting GPCR signaling in situ.
Is reading automatic? Are the ERP correlates of masked priming really lexical?
Authors: Norris Dennis , Kinoshita Sachiko , Hall Jane , Henson Richard
Published: January 2018

Humans have an almost unbounded ability to adapt their behaviour to perform different tasks. In the laboratory, this flexibility is sometimes viewed as a nuisance factor that prevents access to the underlying cognitive mechanisms of interest. For example, in order to study “automatic” lexical processing, psycholinguists have used masked priming or evoked potentials to measure “automatic” lexical processing. However, the pattern of masked priming can be radically altered by changing the task. In lexical decision, priming is observed for words but not for nonwords, yet in a same-different matching task, priming is observed for same responses but not for different responses, regardless of whether the target is a word or a nonword (Norris & Kinoshita, 2008). Here we show that evoked potentials are equally sensitive to the nature of required decision, with the neural activity normally associated with lexical processing being seen for both words and nonwords on same trials, and for neither on different trials. (150)
A meta-analysis of Planarian: an animal model useful to understand the effect of magnetic field Planarian and magnetic field researches
Authors: Gomez Luna Liliana María , Puente López Vivian de la
Published: January 2018

The planarians research since the first description until nowadays has a broad spectrum of topics. The present paper deals on a meta-analysis which identified as a problem the lack of consolidate information and data analysis about the use of planarian as animal model, and specifically the use of magnetic field in regeneration experiments. To conduct the meta-analysis 1255 papers published since 1955 to 2017 were analysed, identifying the Stem cell biology and regeneration as the most published topic, with 276 papers, followed by molecular and cellular analyses (238), genetics (175), inter and transdisciplinary research (107), ecotoxicological evaluations (102), animal model (67), ecological and biological studies (56), magnetic field (57), developmental biology (32) and RNA regulation (31).Other statistics and metrics indicators were taken in to account like total of papers and distribution per year, distribution of paper by journals and selection of main journals according to the number of published papers, most cited papers, authors and countries and distribution of papers by countries. Finally, were analysed those papers with Planarians research using magnetic field, all of them published during the last three years. It was an evidence that this topic is becoming a trending with rising interest, being the most reported species to study the magnetic field effects Dugesia spp. and Girardia sp.

Summary statement

This work presents a meta-analysis which allows consolidating information and a better understanding of trends in Planarian researches, emphasizing in the use of magnetic field.
High-resolution wide-field human brain tumor margin detection and in vivo murine neuroimaging
Authors: Yecies Derek , Liba Orly , SoRelle Elliott , Dutta Rebecca , Yuan Edwin , Vogel Hannes , Grant Gerald A. , de la Zerda Adam
Published: January 2018

Currentin vivoneuroimaging techniques provide limited field of view or spatial resolution and often require exogenous contrast. These limitations prohibit detailed structural imaging across wide fields of view and hinder intraoperative tumor margin detection. Here we present a novel neuroimaging technique, speckle-modulating optical coherence tomography (SM-OCT), which allows us to image the brains of live mice andex vivohuman samples with unprecedented resolution and wide field of view using only endogenous contrast. The increased effective resolution provided by speckle elimination reveals white matter fascicles and cortical layer architecture in the brains of live mice. To our knowledge, the data reported herein represents the highest resolution imaging of murine white matter structure achievedin vivoacross a wide field of view of several millimeters. When applied to an orthotopic murine glioblastoma xenograft model, SM-OCT readily identifies brain tumor margins with near single-cell resolution. SM-OCT ofex vivohuman temporal lobe tissue reveals fine structures including cortical layers and myelinated axons. Finally, when applied to anex vivosample of a low-grade glioma resection margin, SM-OCT is able to resolve the brain tumor margin. Based on these findings, SM-OCT represents a novel approach for intraoperative tumor margin detection andin vivoneuroimaging.
Growth equity and sectoral decompositions of aggregate poverty changes in Cameroon
Authors: Atemnkeng Johannes Tabi , Tambi Daniel Mbu
Published: January 2018

Purpose

The purpose of this paper is to provide insight to policy-makers into a framework for action, which is needed to effectively reduce poverty in its monetary and non-monetary dimensions.

Design/methodology/approach

Specifically, an exact decomposition analysis is conducted that is based on the Shapley value method, and investigated the growth and redistribution effects as well as changes due to mobility and sector-specific effects of the variation in both income/expenditure and non-income poverty dimensions.

Findings

Growth in mean consumption and household assets accounted for the bulk of the improvement in poverty reduction and the results complement the evidence obtained from the “sectoral decomposition” of poverty in Cameroon which may indeed have a strong bearing on the sectoral shares of poverty. The temptation is resisted, however, not to deny that redistribution also has an important role to play, yet there must be severe limits to what can be achieved by growth neutral redistribution. The redistribution effect had an ameliorating tendency in household asset deprivation among farming households.

Originality/value

This paper is a well-written piece using quite rigorous and interesting methodological approach. To obtain a measure of non-income dimensions of well-being, the authors constructed composite indices on household assets reflecting household access to a range of physical assets and services including human capital by polychoric principal component analysis method.
Applying data mining for online CRM marketing strategy
Authors: Chiang Wen-Yu
Published: January 2018

Purpose

The purpose of this paper is to propose a data mining approach for mining valuable markets for online customer relationship management (CRM) marketing strategy. The industry of coffee shops in Taiwan is employed as an empirical case study in this research.

Design/methodology/approach

Via a proposed data mining approach, the study used fuzzy clustering algorithm and Apriori algorithm to analyze customers for obtaining more marketing and purchasing knowledge of online CRM systems.

Findings

The research found three hard markets and one fuzzy market. Furthermore, the study discovered two association rules and two fuzzy association rules.

Originality/value

However, industry of coffee shops has been always a fast-growing and competitive business around the world. Thus, marketing strategy is important for this industry. The results and the proposed data mining approach of this research can be used in the industry of coffee shop or other retailers for their online CRM marketing systems.
Adolescents’ sources for food safety knowledge and trust
Authors: Lange Marie , Göranzon Helen , Fleig Lena , Marklinder Ingela
Published: January 2018

Purpose

The purpose of this paper is to investigate where students in a Swedish compulsory school acquire their knowledge of food safety and how trustworthy they deem them to be.

Design/methodology/approach

A survey of students’ self-reported sources of and trust in food safety knowledge was performed. A student response system was used for data collection, and the students were asked to answer questions presented on a PowerPoint presentation using a small wireless handheld device: a clicker. A questionnaire with 24 questions was used, and the responses were collected at 18 different schools with a total of 529 participants attending school Year 9.

Findings

Mothers were reported as being the most important source of food safety knowledge (38 per cent), especially among girls, and were also given high credibility (36 per cent). Boys reported trusting home and consumer studies (HCS), fathers and media to a higher extent. Girls reported cooking at home more often but, for all students, it was more common to rarely or never cook at home, which is why HCS teaching can be seen as valuable for many students. HCS teaching needs to be improved in order to raise its credibility. About half of the students (51 per cent) reported to have the highest trust for their source of knowledge.

Research limitations/implications

The students could only choose one source of knowledge and trust, although it is usual to learn from many different sources.

Practical implications

HCS teaching needs to get higher credibility among students as a counterweight against other sources.

Social implications

Educated consumers could influence their health.

Originality/value

Limited research has been performed on food safety knowledge among adolescents.
Food safety practices of future food handlers and their teachers, observed during practical lessons
Authors: Ovca Andrej , Jevšnik Mojca , Raspor Peter
Published: January 2018

Purpose

The purpose of this paper is to investigate future food handlers’ practices during practical lessons close to the end of their formal vocational education, and to record teachers’ behaviour and to evaluate classrooms that were intended for practical lessons.

Design/methodology/approach

A total of 90 students between 17 and 19 years of age, 12 teachers, and 12 training classrooms intended for practical lessons, which were divided into six observation sessions in the field of catering and six observation sessions in the field of food processing (bakery, confectionery, and butchery), were observed.

Findings

Both proper and inappropriate food-handling practices were observed among teachers and students. Comparing the hygienic-technical conditions of the training classrooms with teachers’ and students’ behaviour revealed several interconnected situations increasing the risk of food contamination during the production process.

Research limitations/implications

Data were collected by one observer who was not part of the class. The sample size was small, limiting the generalisability of the results.

Practical implications

The results indicate the weaknesses in the formal vocational education of future professional food handlers.

Social implications

Good food safety practices among food handlers reduce societal costs related to health-care systems and food industry economic losses.

Originality/value

The study provides an insight into the education and training of future professional food handlers in a controlled environment in educational institutions.
Tackling the challenges of reducing and managing food waste in Mumbai restaurants
Authors: Bharucha Jehangir
Published: January 2018

Purpose

Around 67 million tons of food is wasted in India every year, which has a value of more than US$14 billion (Haq, 2016). The purpose of this paper is to concentrate on one major source to which the current massive proportion of wastage can be attributed: restaurants. It investigates the statistics, the problem at large, how the restaurants are handling it and recommends ways to better manage the issue.

Design/methodology/approach

A qualitative inquiry has been used. The research population for this study consisted of 63 restaurant owners across Mumbai city and its suburbs. In-depth discussions were held with these restaurant owners/managers in various matters of interest to this study.

Findings

The group of restaurateurs opined that the solution to Mumbai’s restaurants waste management lies in micro management rather than large scale plans. In total, 75 percent of the restaurants have 10-20 percent extra preparation. High-end fine-dining restaurants make even more additional preparations and are the ones more receptive to participating and also sensitive toward importance of waste management. Several of the restaurant owners claim that they can estimate the requirements on specific days of the week. In all, 18 percent of the restaurants surveyed claimed to have a complete dispose of policy. Majority of the restaurants have a clear policy to distribute the surplus food among their staff. Several other innovative strategies were shared.

Research limitations/implications

The restaurant owners/mangers may not have truthfully answered all questions. The participants might have the fear that the authorities would take cognizance of some of the practices that they are following and would have been guarded in their responses. There would always be a fear that the identities would not be kept confidential.

Practical implications

India as a country has been agriculture based for centuries and characterized by massive food production. Yet, people face rampant starvation and malnourishment. This arises to a large extent due to the colossal amounts of food wasted at marriages, restaurants and even by destruction of crops.

Originality/value

The restaurant industry is of critical importance to the Indian economy and while research in India has focused on overall food wastage, studies on restaurant food waste are lacking.
Cooking skills and socio-demographics among Portuguese university students
Authors: Kowalkowska Joanna , Poínhos Rui , Rodrigues Sara
Published: January 2018

Purpose

The purpose of this paper is to assess the reliability of a Portuguese version of the cooking skills scale (CSS) and to evaluate the association between cooking skills and socio-demographic, psychological and other cooking-related variables.

Design/methodology/approach

The study was conducted as an online survey among 730 Portuguese university students. Translation and back-translation of the CSS were performed. Data were assessed in two stages (test and retest) and the psychometric properties of the CSS were analyzed. The effect of socio-demographic variables was assessed by binary logistic regression analysis. The odds ratios for upper tertile of the CSS score were calculated using the lower tertile as reference.

Findings

Cronbach’s α for the CSS was 0.90. In the analysis of test-retest reliability, Spearman’s rank correlation coefficient was 0.79 and Cohen’s κ (for tertiles) was 0.49. Cooking skills were higher in respondents cooking more often, feeling more confident, enjoying more and indicating the personal interest as the main motivation to learn how to cook. Cooking skills were significantly better in females, older students and those with more independent place of residence.

Originality/value

Very good psychometric properties of the Portuguese version of the CSS were found among university students, providing a proper and simple tool to measure cooking skills in future studies with similar populations. The interventions encouraging to acquire and improve cooking skills as part of promoting healthy eating should be targeted especially toward men and young adults.