bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Dependent Resistance to Rhizoctonia solani in Sugar Beet
Authors: Liu Yangxi , Qi Aiming , Khan Mohamed F. R.
Published: April 2019

Rhizoctonia crown and root rot of sugar beet (Beta vulgaris L.), caused by Rhizoctonia solani, continues to be one of the important concerns for the beet industry in Minnesota and North Dakota. Use of resistant cultivars is an important strategy in the management of R. solani in combination with seed treatment and timely fungicide application during the growing season. The objective of this greenhouse study was to determine how sugar beet plants responded to increasing age in resistance to R. solani. Each of three seed companies provided three commercial cultivars with varying R. solani resistance levels: susceptible, moderately resistant, and resistant. Seed were planted at a weekly interval to create different plant age groups from seed to 10-week-old plants, with growing degree days (GDD) ranging from 0 to 1,519 thermal time (°Cd). Seed and plants were all simultaneously inoculated with R. solani AG2-2-infested barley grains. Twenty-eight days after inoculation, plants were pulled and washed, and roots were evaluated for disease severity. All cultivars were highly susceptible to R. solani when inoculated at seed to 3 weeks old (0 to 464°Cd). At 4 and 5 weeks of plant age (617 to 766°Cd), resistant cultivars started to show significant resistance to R. solani. Proportion of the affected roots with disease score ≥ 5 followed a sigmoid response, declining with increased GDD in moderately resistant and resistant cultivars, whereas it continued to decline linearly with increased GDD in susceptible cultivars. This study demonstrated that sugar beet cultivars, regardless of their assigned level of R. solani resistance, were highly susceptible to the pathogen before they reached the six- to eight-leaf stage at 4 to 5 weeks (617 to 766°Cd) after planting. Therefore, additional protection in the form of seed treatment or fungicide application may be required to protect sensitive sugar beet seed and seedlings in fields with a history of R. solani under favorable environmental conditions.
Halyos: A patient-facing visual EHR interface for longitudinal risk awareness
Authors: Mataraso Samson , Socrates Vimig , Lekschas Fritz , Gehlenborg Nils
Published: April 2019

We have developed Halyos (http://halyos.gehlenborglab.org), a visual EHR web application that complements the functionality of existing patient portals. Halyos is designed to integrate with existing EHR systems to help patients interpret their health data. The Halyos application utilizes the SMART on FHIR (Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources) platform to create an interoperable interface that provides interactive visualizations of clinically validated risk scores and longitudinal data derived from a patient’s clinical measurements. These visualizations allow patients to investigate the relationships between clinical measurements and risk over time. By enabling patients to set hypothetical future values for these clinical measurements, patients can see how changes in their health will impact their risks. Using Halyos, patients are provided with the opportunity to actively improve their health based on increased understanding of longitudinal information available in EHRs and to begin a dialogue with their providers.
Targeted Nanopore Sequencing with Cas9 for studies of methylation, structural variants, and mutations
Authors: Gilpatrick Timothy , Lee Isac , Graham James E. , Raimondeau Etienne , Bowen Rebecca , Heron Andrew , Sedlazeck Fritz J , Timp Winston
Published: April 2019

Nanopore sequencing technology can rapidly and directly interrogate native DNA molecules. Often we are interested only in interrogating specific areas at high depth, but conventional enrichment methods have thus far proved unsuitable for long reads1. Existing strategies are currently limited by high input DNA requirements, low yield, short (<5kb) reads, time-intensive protocols, and/or amplification or cloning (losing base modification information). In this paper, we describe a technique utilizing the ability of Cas9 to introduce cuts at specific locations and ligating nanopore sequencing adaptors directly to those sites, a method we term ‘nanopore Cas9 Targeted-Sequencing’ (nCATS).

We have demonstrated this using an Oxford Nanopore MinION flow cell (Capacity >10Gb+) to generate a median 165X coverage at 10 genomic loci with a median length of 18kb, representing a several hundred-fold improvement over the 2-3X coverage achieved without enrichment. We performed a pilot run on the smaller Flongle flow cell (Capacity ~1Gb), generating a median coverage of 30X at 11 genomic loci with a median length of 18kb. Using panels of guide RNAs, we show that the high coverage data from this method enables us to (1) profile DNA methylation patterns at cancer driver genes, (2) detect structural variations at known hot spots, and (3) survey for the presence of single nucleotide mutations. Together, this provides a low-cost method that can be applied even in low resource settings to directly examine cellular DNA. This technique has extensive clinical applications for assessing medically relevant genes and has the versatility to be a rapid and comprehensive diagnostic tool. We demonstrate applications of this technique by examining the well-characterized GM12878 cell line as well as three breast cell lines (MCF-10A, MCF-7, MDA-MB-231) with varying tumorigenic potential as a model for cancer.

Contributions

TG and WT constructed the study. TG performed the experiments. TG, IL, and FS analyzed the data. TG, JG, ER, RB and AH and developed the method. TG and WT wrote the paper
Rapid discovery of synthetic DNA sequences to rewrite endogenous T cell circuits
Authors: Roth Theodore L. , Li P. Jonathan , Nies Jasper F. , Yu Ruby , Nguyen Michelle L.T. , Lee Youjin , Apathy Ryan , Truong Anna , Hiatt Joseph , Wu David , Nguyen David N. , Goodman Daniel , Bluestone Jeffrey A. , Roybal Kole , Shifrut Eric , Marson Alexander
Published: April 2019

Genetically-engineered immune cell therapies have been in development for decades1–3 and recently have proven effective to treat some types of cancer4. CRISPR-based genome editing methods, enabling more flexible and targeted sequence integrations than viral transduction, have the potential to extend the clinical utility of cell therapies5,6. Realization of this potential depends on improved knowledge of how coding and non-coding sites throughout the genome can be modified efficiently and on improved methods to discover novel synthetic DNA sequences that can be introduced at targeted sites to enhance critical immune cell functions. Here, we developed improved guidelines for non-viral genome targeting in human T cells and a pooled discovery platform to identify synthetic genome modifications that enhance therapeutically-relevant cell functions. We demonstrated the breadth of targetable genomic loci by performing large knock-ins at 91 different genomic sites in primary human T cells, and established the power of flexible genome targeting by generating cells with Genetically Engineered Endogenous Proteins (GEEPs) that seamlessly integrate synthetic and endogenous genetic elements to alter signaling input, output, or regulatory control of genes encoding key immune receptors. Motivated by success in introducing synthetic circuits into endogenous sites, we then developed a platform to facilitate discovery of novel multi-gene sequences that reprogram both T cell specificity and function. We knocked in barcoded pools of large DNA sequences encoding polycistronic gene programs. High-throughput pooled screening of targeted knock-ins to the endogenous T cell receptor (TCR) locus revealed a transcriptional regulator and novel protein chimeras that combined with a new TCR specificity to enhance T cell responses in the presence of suppressive conditions in vitro and in vivo. Overall, these pre-clinical studies provide flexible tools to discover complex synthetic gene programs that can be written into targeted genome sites to generate more effective therapeutic cells.
Neutrophils use selective autophagy receptor p62/SQSTM1 to targetStaphylococcus aureusfor degradationin vivoin zebrafish
Authors: Gibson Josie F , Prajsnar Tomasz K , Hill Christopher J , Tooke Amy K , Serba Justyna J , Tonge Rebecca D , Foster Simon J , Grierson Andrew J , Ingham Philip W , Renshaw Stephen A , Johnston Simon A
Published: April 2019

Autophagy leads to degradation of cellular components and has an important role in restricting intracellular pathogens. Autophagy receptors, including p62, target invading intracellular pathogens to the autophagy pathway for degradation.Staphylococcus aureusis a significant pathogen of humans and often life-threatening in the immunocompromised. Increasing evidence demonstrates thatS. aureusis an intracellular pathogen of immune cells and may use neutrophils as proliferative niche but the intracellular fate ofS. aureusfollowing phagocytosis by neutrophils has not previously been analysedin vivo. In vitro, p62 is able to co-localise with intracellularStaphylococcus aureus, but whether p62 is beneficial or detrimental in host defence againstS. aureus in vivohad not been determined.

Here we use zebrafish to determine the fate and location ofS. aureuswithin neutrophils throughout infection. We show that Lc3 and p62 recruitment to phagocytosedS. aureusis altered depending on the bacterial location within the neutrophil. We also show rapid Lc3 marking of bacterial phagosomes within neutrophils which may be associated with subsequent bacterial degradation. Finally, we find that p62 is important for controlling cytosolic bacteria demonstrating for the first time a key role of p62 in autophagic control ofS. aureusin neutrophils.
CRISPR-Cas9-assisted native end-joining editing offers a simple strategy for efficient genetic engineering in Escherichia coli
Authors: Huang Chaoyong , Ding Tingting , Wang Jingge , Wang Xueqin , Wang Jialei , Zhu Lin , Bi Changhao , Zhang Xueli , Ma Xiaoyan , Huo Yi-Xin
Published: April 2019

Unlike eukaryotes, bacteria are less proficient in homologous recombination (HR) and non-homologous end joining (NHEJ). All existing genomic editing methods for Escherichia coli rely on exogenous HR or NHEJ systems to repair DNA double-strand breaks (DSBs). Although an E. coli native end-joining (ENEJ) system has been reported, its potential in chromosomal engineering has not yet been explored. Here, we present a CRISPR-Cas9-assisted native end-joining editing and show that ENEJ-dependent DNA repair can be used to conduct rapid and efficient knocking-out of E. coli genomic sequence of up to 83 kb. Moreover, the positive rate and editing efficiency is independent of high-efficiency competent cells. The method requires neither exogenous DNA repair systems nor introduced editing template. The Cas9 complex is the only foreign element in this method. This study is the first successful engineering effort to utilize ENEJ mechanism in genomic editing and provides an effective strategy for genetic engineering in bacteria that are inefficient in HR and NHEJ.

Significance

The application in prokaryotes is difficult because of the weak homologous recombination and non-homologous end joining systems. E. coli, as the most-used prokaryote in metabolic engineering, has no NHEJ system. All existing genomic editing methods for E. coli rely on exogenous HR or NHEJ systems to repair double-strand breaks introduced by CRISPR/Cas9. In this report, we firstly demonstrate that the weak and previously ignored end-joining mechanism in E. coli can be used for efficient large-scale genetic engineering assisted by CRISPR/Cas9. Our efforts greatly simplify the genomic editing procedure of E. coli and provide an effective strategy for genetic engineering in bacteria that are inefficient in HR and NHEJ.
Light-sheet microscopy with isotropic, sub-micron resolution and solvent-independent large-scale imaging
Authors: Chakraborty Tonmoy , Driscoll Meghan , Murphy Malea , Roudot Philippe , Chang Bo-Jui , Vora Saumya , Wong Wen Mai , Nielson Cara , Zhang Hua , Zhemkov Vladimir , Hiremath Chitkale , De La Cruz Estanislao Daniel , Bezprozvanny Ilya , Zhao Hu , Tomer Raju , Heintzmann Rainer , Meeks Julian , Marciano Denise , Morrison Sean , Danuser Gaudenz , Dean Kevin M. , Fiolka Reto
Published: April 2019

We present cleared tissue Axially Swept Light-Sheet Microscopy (ctASLM), which achieves sub-micron isotropic resolution, high optical sectioning capability, and large field of view imaging (870×870 μm2) over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and organic chemically cleared tissue preparations and provides 2- to 5-fold better axial resolution than confocal or other reported cleared tissue light-sheet microscopes. We image millimeter-sized tissues with sub-micron 3D resolution, which enabled us to perform automated detection of cells and subcellular features such as dendritic spines.
Automated Reconstruction of a Serial-Section EM Drosophila Brain with Flood-Filling Networks and Local Realignment
Authors: Li Peter H. , Lindsey Larry F. , Januszewski Michał , Zheng Zhihao , Bates Alexander Shakeel , Taisz István , Tyka Mike , Nichols Matthew , Li Feng , Perlman Eric , Maitin-Shepard Jeremy , Blakely Tim , Leavitt Laramie , Jefferis Gregory S.X.E. , Bock Davi , Jain Viren
Published: April 2019

Reconstruction of neural circuitry at single-synapse resolution is a key target for improving understanding of the nervous system in health and disease. Serial section transmission electron microscopy (ssTEM) is among the most prolific imaging methods employed in pursuit of such reconstructions. We demonstrate how Flood-Filling Networks (FFNs) can be used to computationally segment a forty-teravoxel whole-brain Drosophila ssTEM volume. To compensate for data irregularities and imperfect global alignment, FFNs were combined with procedures that locally re-align serial sections as well as dynamically adjust and synthesize image content. The proposed approach produced a largely merger-free segmentation of the entire ssTEM Drosophila brain, which we make freely available. As compared to manual tracing using an efficient skeletonization strategy, the segmentation enabled circuit reconstruction and analysis workflows that were an order of magnitude faster.
Environmental drivers define contrasting microbial habitats, diversity, and community structure in Lake Baikal, Siberia
Authors: Wilburn Paul , Shchapov Kirill , Theriot Edward C. , Litchman Elena
Published: April 2019

Understanding how microbial communities respond to environmental change requires knowing the main drivers of their structure, diversity and potential resilience. Lake Baikal is the world’s most ancient, deep, voluminous, and biodiverse lake, holding 20 percent of unfrozen fresh water that is undergoing rapid warming. Despite its global importance, little is known about Baikal’s bacterioplankton communities and their drivers. In this extensive survey, we show that temperature, along with stratification, nutrients, and dissolved oxygen, but not geographic distance, define major microbial habitats and community similarity. Mixed layer and deep water communities exhibited contrasting patterns of richness, diversity and evenness, and comprised different cohesive modules in the whole Baikal OTU co-occurrence network. The network’s small-world properties indicated likely resistance to perturbations but sensitivity to abundance changes of central, most connected OTUs. Previous studies showed Baikal water temperature rising by over 1.2°C since 1946, and this trend is predicted to accelerate. Because temperature emerged as the most significant predictor of the mixed layer community structure, we hypothesize that it is most likely to drive future community changes. Understanding how temperature and other abiotic factors structure microbial communities in this and other rapidly changing ecosystems will allow better predictions of ecosystem responses to anthropogenic stressors.
Comparison of different extraction kits to isolate microRNA fromGalleria mellonella(wax moth) larvae infected withMetarhizium brunneum(ARSEF4556)
Authors: Alenezi Muneefah A. , Butt Tariq M. , Eastwood Daniel C.
Published: April 2019

MicroRNAs (miRNAs) play an important role in regulating gene expression and are involved in developmental processes in animals, plants and fungi. To understand the role of miRNAs in a biological system, it is important to optimise the extraction procedures to obtain high quality and quantity nucleic acid that enable high throughput sequencing and expression analysis. Numerous kit-based miRNA extraction protocols have been optimised generally to single cell or tissue cultures. Fungi, however, often occupy physically and chemically complex environments which miRNA make extraction challenging, such as fungal pathogens interacting within plant or animal host tissue. We used aGalleria mellonella(wax moth) larvae and entomopathogenic fungusMetarhizium brunneum ARSEF 4556host/pathogen model to compare commercially available miRNA extraction kits (Invitrogen PureLink™ miRNA Isolation Kit, Ambion mirVana™miRNA Isolation Kit and Norgen microRNA purification Kit). Our results showed reproducible and significant differences in miRNAs extraction between the kits, with the Invitrogen PureLink™ miRNA Isolation protocol demonstrating the best performance in terms of miRNA quantity, quality and integrity isolated from fungus-infected insect tissue.
TMS of V1 eliminates unconscious processing of chromatic stimuli
Authors: Hurme Mikko , Koivisto Mika , Henriksson Linda , Railo Henry
Published: April 2019

Some of the neurological patients with primary visual cortex (V1) lesions can guide their behavior based on stimuli presented to their blind visual field. One example of this phenomenon is the ability to discriminate colors in the absence of awareness. These so-called patients with blindsight must have a neural pathway that bypasses the V1, explaining their ability to unconsciously process stimuli. To test if similar pathways function in neurologically healthy individuals or if unconscious processing depends on the V1, we disturbed the visibility of a chromatic stimulus with metacontrast masking (Experiment 1) or transcranial magnetic stimulation (TMS) of the V1 (Experiment 2). We measured unconscious processing using the redundant target effect (RTE), which is the speeding up of reaction times in response to dual stimuli compared with one stimulus, when the task is to respond to any number of stimuli. An unconscious chromatic RTE was found when the visibility of the redundant chromatic stimulus was suppressed with a visual mask. When TMS was applied to the V1 to disturb the perception of the redundant chromatic stimulus, the RTE was eliminated. Based on our results and converging evidence from previous studies, we conclude that the unconscious processing of chromatic information depends on the V1 in neurologically healthy participants.
Indomethacin-induced gut damage in a surrogate insect model,Galleria mellonella
Authors: Emery Helena , Johnston Richard , Rowley Andrew F. , Coates Christopher J.
Published: April 2019

Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased ‘leakiness’ in rat models, and is used routinely as an assay to screen novel compounds for repair and restitution properties. We set out to establish conditions for indomethacin-induced gut damage in wax-moth (Galleria mellonella) larvae with a view to reducing the need for rodents in such experimentation. We administered indomethacin (1 – 7.5 μg/larva) toG. mellonellavia intrahaemocoelic injection and gavage (force-feeding) and monitored larval survival and development, blood cell (haemocyte) numbers, and changes in gut permeability. Increased levels of gut leakiness were observed within the first 4 to 24-hours by tracking fluorescent microspheres in the faeces and haemolymph (blood equivalent). Additionally, we recorded varying levels of tissue damage in histological sections of the insect midgut, including epithelial sloughing and cell necrosis. Degeneration of the midgut was accompanied by significant increases in detoxification-associated activities (superoxide dismutase and glutathione-S-transferase). Herein, we present the first evidence thatG. mellonellalarvae force-fed indomethacin display broad symptoms of gastric damage similar to rodent models.
Rescuing the attentional performance of rats with cholinergic losses by the M1 positive allosteric modulator TAK-071
Authors: Kucinski Aaron , Phillips Kyra B. , Cherian Ajeesh Koshy , Sarter Martin
Published: April 2019

Loss of basal forebrain cholinergic neurons contributes to the severity of the cognitive decline in age-related dementia and to impairments in gait and balance, and the resulting risks for falls, in patients with Parkinson’s disease (PD). Contrasting with the extensive evidence indicating an essential role of cholinergic activity in mediating cognitive, specifically attentional abilities, treatment with conventional acetylcholinesterase inhibitors (AChEIs) has not fulfilled the promise of efficacy of pro-cholinergic treatments. Here we investigated the potential usefulness of a muscarinic M1 positive allosteric modulator (PAM) in an animal model of cholinergic loss-induced impairments in attentional performance. Given evidence indicating that fast, transient cholinergic signaling mediates the detection of cues in attentional contexts, we hypothesized that an M1 PAM amplifies such transient signaling, thereby enhancing and rescuing attentional performance. Rats performed an operant sustained attention task (SAT), including in the presence of a distractor (dSAT) and during a post-distractor (post-dSAT) period assessing their capacity for recovering performance. Basal forebrain infusions of the cholino-specific immunotoxin 192 IgG-saporin impaired SAT performance, and greater cholinergic losses predicted lower post-dSAT performance recovery. Administration of TAK-071 (0.1, 0.3 mg/kg, p.o., administered over 6-day blocks) improved the performance of all rats during the post-dSAT period (main effect of dose). Drug-induced improvement of post-dSAT performance was relatively greater in lesioned rats, irrespective of sex, and also manifested in female control rats. TAK-071 primarily improved perceptual sensitivity (d’) in lesioned rats and facilitated the adoption of a more liberal response bias (B”D) in all female rats. Collectively, these findings suggest that TAK-071 may benefit the attentional performance of patients with partial cholinergic losses and specifically in situations that tax top-down, or goal-driven, attentional control.
MCHM acts as a hydrotrope, altering the balance of metals in yeast
Authors: Pupo Amaury , Ayers Michael C. , Sherman Zachary N. , Vance Rachel J. , Cumming Jonathan R. , Gallagher Jennifer E.G.
Published: April 2019

While drugs and other industrial chemicals are routinely studied to assess risks, many widely-used chemicals have not been thoroughly evaluated. One such chemical, 4-methylcyclohexane methanol (MCHM), is an industrial coal-cleaning chemical that contaminated the drinking-water supply in Charleston, WV, USA in 2014. While a wide range of ailments was reported following the spill, little is known about the molecular effects of MCHM exposure. We used the yeast model to explore the impacts of MCHM on cellular function. Exposure to MCHM dramatically altered the yeast transcriptome and the balance of metals in yeast. Underlying genetic variation in the response to MCHM and transcriptomics and mutant analysis uncovered the role of the metal transporters, Arn2 and Yke4, to MCHM response. Expression of Arn2, involved in iron uptake, was lower in MCHM-tolerant yeast and loss of Arn2 further increased MCHM tolerance. Genetic variation within Yke4, an ER zinc transporter, also mediated response to MCHM and loss of Yke4 decreased MCHM tolerance. The addition of zinc to MCHM-sensitive yeast rescued growth inhibition.In vitroassays demonstrated that MCHM acted as a hydrotrope and prevented protein-interactions, while zinc-induced the aggregation of proteins. We hypothesized that MCHM altered the structures of extracellular domains of proteins, and the addition of zinc stabilized the structure to maintain metal homeostasis in yeast exposed to MCHM.
Genetic screens identify multiple negative regulators that additively restrict recruitment of the SWI/SNF chromatin remodeler to theHOpromoter inSaccharomyces cerevisiae
Authors: Parnell Emily J. , Stillman David J.
Published: April 2019

Activation of theSaccharomyces cerevisiae HOpromoter is highly regulated, requiring the ordered recruitment of activators and coactivators and allowing production of only a few transcripts in mother cells within a short cell cycle window. We conducted genetic screens to identify the negative regulators ofHOexpression necessary to limitHOtranscription. Known repressors ofHO(Ash1 and Rpd3) were identified, as well as several additional chromatin-associated factors including the Hda1 histone deacetylase, the Isw2 chromatin remodeler, and the corepressor Tup1. We also identified clusters ofHOpromoter mutations that suggested roles for the Dot6/Tod6 (PAC site) and Ume6 repression pathways. We used ChIP assays with synchronized cells to validate the involvement of these factors and map the association of Ash1, Dot6, and Ume6 with theHOpromoter to a brief window in the cell cycle between binding of the initial activating transcription factor and initiation of transcription. We found that Ash1 and Ume6 each recruit the Rpd3 histone deacetylase toHO,and their effects are additive. In contrast, Rpd3 was not recruited significantly to the PAC site, suggesting this site has a distinct mechanism for repression. Increases inHOexpression and SWI/SNF recruitment were all additive upon loss of Ash1, Ume6, and PAC site factors, indicating the convergence of independent pathways for repression. Our results demonstrate that multiple protein complexes are important for limiting the spread of SWI/SNF mediated nucleosome eviction across theHOpromoter, suggesting that regulation requires a delicate balance of activities that promote and repress transcription.
Stochastic Lanczos estimation of genomic variance components for linear mixed-effects models
Authors: Border Richard , Becker Stephen
Published: April 2019

Background

Linear mixed-effects models (LMM) are a leading method in conducting genome-wide association studies (GWAS) but require residual maximum likelihood (REML) estimation of variance components, which is computationally demanding. Previous work has reduced the computational burden of variance component estimation by replacing direct matrix operations with iterative and stochastic methods and by employing loose tolerances to limit the number of iterations in the REML optimization procedure. Here, we introduce two novel algorithms,stochastic Lanczos derivative-free REML(SLDF_REML) andLanczos first-order Monte Carlo REML(L_FOMC_REML), that exploit problem structure via the principle of Krylov subspace shift-invariance to speed computation beyond existing methods. Both novel algorithms only require a single round of computation involving iterative matrix operations, after which their respective objectives can be repeatedly evaluated using vector operations. Further, in contrast to existing stochastic methods,SLDF_REMLcan exploit precomputed genomic relatedness matrices (GRMs), when available, to further speed computation.

Results

Results of numerical experiments are congruent with theory and demonstrate that interpreted-language implementations of both algorithms match or exceed existing compiled-language software packages in speed, accuracy, and flexibility.

Conclusions

Both theSLDF_REMLandL_FOMC_REMLalgorithms outperform existing methods for REML estimation of variance components for LMM and are suitable for incorporation into existing GWAS LMM software implementations.

Full list of author information is available at the end of the article
Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicitAedes aegyptipopulations
Authors: Sánchez C. Héctor M. , Bennett Jared B. , Wu Sean L. , Rašić Gordana , Akbari Omar S. , Marshall John M.
Published: April 2019

Background

The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently-engineered threshold-dependent gene drive systems - reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL- to explore their ability to be confined and remediated.

Results

We simulate releases ofAedes aegypti, the mosquito vector of dengue, Zika and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMELrequires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely.

Conclusions

Our analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes intoAe. aegyptipopulations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.
Interspecies signaling generates exploratory motility in Pseudomonas aeruginosa
Authors: Limoli Dominique H. , Donegan Niles P. , Warren Elizabeth A. , Cheung Ambrose L. , O’Toole George A.
Published: April 2019

Microbes often live in multispecies communities where interactions among community members impact both the individual constituents and the surrounding environment. Here, we developed a system to visualize interspecies behaviors at initial encounters. By imaging two prevalent pathogens known to be coisolated from chronic illnesses, Pseudomonas aeruginosa and Staphylococcus aureus, we observed P. aeruginosa can modify surface motility in response to secreted factors from S. aureus. Upon sensing S. aureus, P. aeruginosa transitioned from collective to single-cell motility with an associated increase in speed and directedness – a behavior we refer to as ‘exploratory motility’. Through modulation of cAMP, explorer cells moved preferentially towards S. aureus and invaded S. aureus colonies through the action of the type IV pili. These studies reveal previously undescribed motility behaviors and lend insight into how P. aeruginosa senses and responds to other species. Identifying strategies to harness these interactions may open avenues for new antimicrobial strategies.
Assessing the viability of biochemical networks across planets
Authors: Smith Harrison B. , Drew Alexa , Walker Sara I.
Published: April 2019

The concept of the origin of life implies that initially, life emerged from a non-living medium. If this medium was Earth’s geochemistry, then that would make life, by definition, a geochemical process. The extent to which life on Earth today could subsist outside of the geochemistry from which it is embedded is poorly quantified. By leveraging large biochemical datasets in conjunction with planetary observations and computational tools, this research provides a methodological foundation for the quantitative assessment of our biology’s viability in the context of other geospheres. Investigating a case study of alkaline prokaryotes in the context of Enceladus, we find that the chemical compounds observed on Enceladus thus far would be insufficient to allow even these extremophiles to produce the compounds necessary to sustain a viable metabolism. The environmental precursors required by these organisms provides a map for the compounds which should be prioritized for detection in future planetary exploration missions. The results of this framework have further consequences in the context of planetary protection, and hint that forward contamination may prove infeasible without meticulous intent.
Proteases as Biological Bits for Programmable Medicine
Authors: Holt Brandon Alexander , Kwong Gabriel A.
Published: April 2019

Engineered biocircuits that interface with living systems as plug-and-play constructs may enable new applications for programmable therapies and diagnostics. We create biological bits (bbits) using proteases – a family of pleiotropic, promiscuous enzymes – to construct the biological equivalent of Boolean logic gates, comparators and analog-to-digital converters. We use these modules to write a cell-free bioprogram that can combine with bacteria-infected blood, quantify infection burden, and then calculate and unlock a selective drug dose. Inspired by probabilistic computing, we leverage multi- and common-target protease promiscuity as the biological analog of superposition to program three probabilistic bbits that solve all implementations of the two-bit oracle problem, Learning Parity with Noise. Treating a network of dysregulated proteases in a living animal as an oracle, we use this algorithm to resolve the probability distribution of coagulation proteases in vivo, allowing diagnosis of pulmonary embolism with high sensitivity and specificity (AUROC = 0.92) in a mouse model of thrombosis. Our results demonstrate that protease activity can be programmed in cell-free systems to carry out classical and probabilistic algorithms for programmable medicine.
Angular dispersion enhanced prebunch for seeding ultrashort and coherent EUV and soft X-ray free-electron laser in storage rings
Authors: Wang Xiaofan , Feng Chao , Liu Tao , Zhang Zhen , Tsai Cheng-Ying , Wu Juhao , Yang Chuan , Zhao Zhentang
Published: April 2019

Prebunching is an effective technique to reduce the radiation saturation length and to improve the longitudinal coherence and output stability in storage-ring-based free-electron lasers (FELs). A novel technique is proposed which uses angular dispersion to enhance the high-harmonic bunching with very small laser-induced energy spread. This technique can effectively reduce the radiation saturation length without significantly reducing the peak power of the FEL. Numerical simulations demonstrate that this technique can be used for the generation of 100 MW scale level, fully temporal coherent femtosecond extreme-ultraviolet and soft X-ray radiation pulses through a 10 m-long undulator based on a diffraction-limited storage ring.
Crystal structures and Hirshfeld surface analysis of 2-(adamantan-1-yl)-5-(4-fluorophenyl)-1,3,4-oxadiazole and 2-(adamantan-1-yl)-5-(4-chlorophenyl)-1,3,4-oxadiazole
Authors: Al-Wahaibi Lamya H. , Alsfouk Aisha , El-Emam Ali A. , Blacque Olivier
Published: April 2019

The crystal structures of the title adamantane-oxadiazole hybrid compounds, C18H19FN2O (I) and C18H19ClN2O (II), are built up from an adamantane unit and a halogenophenyl ring, [X = F (I), Cl (II)], in position 5 on the central 1,3,4-oxadiazole unit. The molecular structures are very similar, only the relative orientation of the halogenophenyl ring in comparison with the central five-membered ring differs slightly. In the crystals of both compounds, molecules are linked by pairs of C—H...N hydrogen bonds, forming inversion dimers with R
2
2(12) ring motifs. In (I) the dimers are connected by C—H...F interactions, forming slabs lying parallel to the bc plane. In (II), the dimers are linked by C—H...π and offset π–π interactions [interplanar distance = 3.4039 (9) Å], forming layers parallel to (10\overline{1}).
Tris(μ2-2-methoxy-6-{[(2-sulfidoethyl)imino]methyl}phenolato)trinickel(II) dimethylformamide monosolvate: crystal structure, spectroscopic characterization and antibacterial activity
Authors: Rusanova Julia A. , Kokozay Vladimir N. , Pokas Olena V.
Published: April 2019

The title trinuclear nickel(II) complex, [Ni3(C10H11NO2S)3]·C3H7NO, with a Schiff base ligand formed in situ from 2-aminoethanethiol and o-vanillin crystallizes in the orthorhombic space group Pbca. Its asymmetric unit consists of one neutral Ni3
L
3 molecule and one DMF solvent molecule. The solid-state organization of the complex can be described as an insertion of the solvent molecules within the crystallographically independent trinuclear NiII species. Several C—H...π edge-to-face interactions and π–π stacking interactions link the components in the crystal. A first example of a short intermolecular C—H...Ni contact is found. Antibacterial in vitro screening revealed that the title compound has antibacterial activity, the best effect being against Acinetobacter baumannii.
Crystal structure of bis{μ-2-methoxy-6-[(methylimino)methyl]phenolato}bis({2-methoxy-6-[(methylimino)methyl]phenolato}nickel(II)) involving different coordination modes of the same Schiff base ligand
Authors: Vassilyeva Olga Yu. , Kokozay Vladimir N. , Skelton Brian W.
Published: April 2019

The structure of the title compound, [Ni2(C9H10NO2)4], is built up by discrete centrosymmetric dimers. Two nitrogen and three oxygen atoms of two Schiff base ligands singly deprotonated at the phenolate site form a square-pyramidal environment for each metal atom. The ligands are bonded differently to the metal centre: one of the phenolic O atoms is bound to one nickel atom, whereas another bridges the two metal atoms to form the dimer. The Ni—N/O distances fall in the range 1.8965 (13)–1.9926 (15) Å, with the Ni—N bonds being slightly longer; the fifth contact of the metal to the bridging phenolate oxygen atom is substantially elongated [2.533 (1) Å]. A similar coordination geometry was observed in the isomorphous Cu analogue previously reported by us [Sydoruk et al. (2013). Acta Cryst. E69, m551–m552]. In the crystal, the [Ni2
L
4] molecules form sheets parallel to the ab plane with the polar methoxy groups protruding into the intersheet space and keeping the sheets apart. Within a sheet, the molecules are stacked relative to each other in such a way that the Ni2O2 planes of neighbouring molecules are orthogonal.
The early bird and the late bird: which catches more worms in Australia?
Authors: Jayawardena Nirodha Imali , Omura Akihiro , Li Bin
Published: April 2019

Purpose

The purpose of this paper is to examine what the optimal time is in a typical trading day for investors to buy/sell stocks in the Australian stock market.

Design/methodology/approach

The study mainly focuses on the S&P/ASX200. Each trading day, between 10:00 a.m. and 4:00 p.m., is divided into 30-min blocks. The effectiveness of easily implementable trading strategy to purchase the index in the morning and sell at the close is tested. The study controls for the excess overnight price volatility to improve the effectiveness of the investment strategy. This trading strategy is compared against other 66 possible day-trading combinations.

Findings

The results show that the trading strategy of buying in the first 30 min of the trading session and close off the position during the last 30 min obtains higher returns than other 66 strategies.

Practical implications

The day-trading strategy proposed in this study is very simple and therefore can be easily implemented by investors including individual investors.

Originality/value

To the best of our knowledge, this is the first study which constructs a trading strategy using the J- or U-shaped intraday return pattern.
Financial inclusion and financial sector development in Sub-Saharan Africa: a panel VAR approach
Authors: Anarfo Ebenezer Bugri , Abor Joshua Yindenaba , Osei Kofi Achampong , Gyeke-Dako Agyapomaa
Published: April 2019

Purpose

The purpose of this paper is to investigate the dynamic link between financial inclusion and financial sector development (FSD) in Sub-Saharan Africa.

Design/methodology/approach

This paper employs a panel vector autoregressive framework to examine the dynamic link between financial inclusion and FSD in Sub-Saharan Africa.

Findings

The findings indicate that there is a reverse causality between FSD and financial inclusion in both the Sub-Saharan Africa countries sample and the full sample. It is evident that financial inclusion is a driver of FSD and vice versa.

Practical implications

The practical implication of this study is that financial inclusion should not only be pursued as a policy objective but it could also be an outcome variable of FSD and vice versa. This implies that African economies and governments in their effort to enhance financial inclusion, FSD can serve as a policy tool. This means that policies aimed at promoting financial inclusion will not impede FSD because the two are complementary. This suggests that we can achieve financial inclusion without sacrificing FSD and vice versa.

Originality/value

This paper provides first empirical evidence of the link between financial inclusion and FSD from the Sub-Saharan Africa perspective using data sourced from World Development Indicators spanning from 1990 to 2014 for 48 Sub-Saharan African economies and 217 economies in the world for the full sample.
What can Somali community talk about mental health tell us about our own? Contextualizing the symptoms of mental health
Authors: Ryan Juanita , Thompson Guerin Pauline B. , Elmi Fatuma Hussein , Guerin Bernard
Published: April 2019

Purpose

The purpose of this paper is to review all the research on Somali refugee communities’ “explanatory models” of “mental health” or psychological suffering, and also report original research in order to allow for more contexts on their “mental health” terms to emerge.

Design/methodology/approach

The authors talked in a conversational manner with a small number (11) of Somali people (10 females and 1 male), but this was done intensively over time and on multiple occasions. They discussed their community terms for “mental health” issues but in their own contexts and with their own examples.

Findings

The results showed that Somali as a community had three main groupings of symptoms: Jinn or spirit possession; waali or “craziness”; and a group of terms for serious anxieties, rumination, worrying and thinking too much. What was new from their broader descriptions of context was that the community discourses were based on particular contexts of the person and their behavior within their life history, rather than aiming to universal categories like the DSM.

Practical implications

Both research and practice on mental health should focus less on universal diagnoses and more on describing the contexts in which the symptoms emerge and how to change those contexts, especially with refugee and other less well-understood groups.

Originality/value

The review and original results support symptom-based or contextual approaches to mental health; we should treat the “mental health” symptoms in their life contexts rather than as a disease or disorder. We can learn from how Somali describe their “mental health” symptoms rather than treat their descriptions as crude forms of the “correct” western diagnostics.
Effect of electron beam surface melting on the microstructure and wear behavior of Stellite 12 hardfacing
Authors: Alhattab Ali Abdul Munim , Dilawary Shaikh Asad Ali , Motallebzadeh Amir , Arisoy Cevat Fahir , Cimenoglu Huseyin
Published: April 2019

Purpose

The purpose of this study is to investigate the effect of electron beam surface melting (EBSM) on the properties of Plasma Transfer Arc (PTA) deposited Stellite 12 hardfacing.

Design/methodology/approach

For this purpose, structural characterization and dry sliding wear tests have been conducted on the hardfacings at room temperature. The wear tracks formed on the surfaces of the hardfacings were examined by a stylus-type profilometer and a scanning electron microscope.

Findings

Refinement of the matrix and the carbides following EBSM process led to about 15 per cent increment in hardness as compared to PTA state. Despite an increase in the surface hardness, EBSM’ed hardfacing exhibited about 50 per cent lower sliding wear resistance than PTA hardfacing against alumina ball. According to the worn surface examinations, reduction in the wear resistance of Stellite 12 after EBSM process has been associated with the extensive refinement of the carbides which made them easier to be removed from the matrix during the sliding contact.

Originality/value

The authors of current study have applied EBSM to PTA deposited Stellite 12 hardfacing alloy to investigate if the surface structure and properties could be improved. More specifically the dry sliding wear performance of PTA and EBSM’ed hardfacings have been focused in the scope of this study. To the best of the authors’ knowledge, this approach, i.e. use of EBSM as a post deposition treatment of Stellite 12 hardfacings, has not been reported in open literature.
How many facets does a “social robot” have? A review of scientific and popular definitions online
Authors: Sarrica Mauro , Brondi Sonia , Fortunati Leopoldina
Published: April 2019

Purpose

On the verge of what has been hailed as the next technological revolution, the purpose of this paper is to examine scientific and popular definitions of the social robot, reflecting on how expert and lay spheres of knowledge interact. Drawing on social representations theory, this paper aims to elucidate how social robots are named and classified, and to examine the dynamics contributing to their definition.

Design/methodology/approach

Scientific and popular definitions of the social robot were investigated by conducting: a systematic review of relevant articles published from 2009 to 2015 in the International Journal of Social Robotics; an analysis of the definitions retrievable from the scientific literature using Google Scholar; and an assessment of the interest in the public sphere, and of the popular definitions retrievable online (by inputting “social robot” in Google Trends, and in Google).

Findings

Scientific definitions of the social robot adopt two strategies, one drawing on and merging previous definitions, the other proposing new, visionary, forward-looking definitions. Popular online definitions of social robots attribute new emotional, linguistic and social capabilities to their physical body.

Research limitations/implications

The findings need to be confirmed by further research, given the limited size of the data sets considered, and the distortions in the data due to filters and the opacity of the online tools employed.

Originality/value

Both scientific and non-scientific definitions see social robots as being capable of interacting with and working for humans, but attribute them a different degree of (functional or full) autonomy. In future, any controversy over the connotation of social robots is likely to concern their sociality and autonomy rather than their functionality.