bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTUnderstanding 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

ABSTRACTMicroRNAs (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

AbstractSome 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

AbstractIndomethacin 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

AbstractLoss 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

AbstractWhile 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

AbstractActivation 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

AbstractBackgroundLinear 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.ResultsResults 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.ConclusionsBoth 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

AbstractBackgroundThe 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.ResultsWe 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.ConclusionsOur 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

AbstractMicrobes 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

AbstractThe 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

AbstractEngineered 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.
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

PurposeThe purpose of this paper is to investigate the dynamic link between financial inclusion and financial sector development (FSD) in Sub-Saharan Africa.Design/methodology/approachThis paper employs a panel vector autoregressive framework to examine the dynamic link between financial inclusion and FSD in Sub-Saharan Africa.FindingsThe 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 implicationsThe 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/valueThis 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.