bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification and selection of ictogenic zones in epilepsy surgery
Authors: Laiou Petroula , Avramidis Eleftherios , Lopes Marinho A. , Abela Eugenio , Müller Michael , Akman Ozgur E. , Richardson Mark P. , Rummel Christian , Schindler Kaspar , Goodfellow Marc
Published: April 2019

Network models of brain dynamics provide valuable insight into the healthy functioning of the brain and how this breaks down in disease. A pertinent example is the use of network models to understand seizure generation (ictogenesis) in epilepsy. Recently, computational models have emerged to aid our understanding of seizures and to predict the outcome of surgical perturbations to brain networks. Such approaches provide the opportunity to quantify the effect of removing regions of tissue from brain networks and thereby search for the optimal resection strategy.

Here, we use computational models to elucidate how sets of nodes contribute to the ictogenicity of networks. In small networks we fully elucidate the ictogenicity of all possible sets of nodes and demonstrate that the distribution of ictogenicity across sets depends on network topology. However, the full elucidation is a combinatorial problem that becomes intractable for large networks. Therefore, we develop a global optimisation approach to search for minimal sets of nodes that contribute significantly to ictogenesis. We demonstrate the potential applicability of these methods in practice by identifying optimal sets of nodes to resect in networks derived from 20 individuals who underwent resective surgery for epilepsy.
Within-family studies for Mendelian randomization: avoiding dynastic, assortative mating, and population stratification biases
Authors: Brumpton Ben , Sanderson Eleanor , Hartwig Fernando Pires , Harrison Sean , Vie Gunnhild Åberge , Cho Yoonsu , Howe Laura D , Hughes Amanda , Boomsma Dorret I , Havdahl Alexandra , Hopper John , Neale Michael , Nivard Michel G , Pedersen Nancy L , Reynolds Chandra A , Tucker-Drob Elliot M , Grotzinger Andrew , Howe Laurence , Morris Tim , Li Shuai ,   MR within-family Consortium, Chen Wei-Min , Bjørngaard Johan Håkon , Hveem Kristian , Willer Cristen , Evans David M , Kaprio Jaakko , Åsvol Bjørn Olav , Smith George Davey , Åsvold Bjørn Olav , Hemani Gibran , Davies Neil M
Published: April 2019

Mendelian randomization (MR) is a widely-used method for causal inference using genetic data. Mendelian randomization studies of unrelated individuals may be susceptible to bias from family structure, for example, through dynastic effects which occur when parental genotypes directly affect offspring phenotypes. Here we describe methods for within-family Mendelian randomization and through simulations show that family-based methods can overcome bias due to dynastic effects. We illustrate these issues empirically using data from 61,008 siblings from the UK Biobank and Nord-Trøndelag Health Study. Both within-family and population-based Mendelian randomization analyses reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while MR estimates from population-based samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects largely disappeared in within-family MR analyses. We found differences between population-based and within-family based estimates, indicating the importance of controlling for family effects and population structure in Mendelian randomization studies.
Conserved DNA polymorphisms distinguish species in the eastern North American white oak syngameon: Insights from an 80-SNP oak DNA genotyping toolkit
Authors: Hipp Andrew L. , Whittemore Alan T. , Garner Mira , Hahn Marlene , Fitzek Elisabeth , Guichoux Erwan , Cavender-Bares Jeannine , Gugger Paul F. , Manos Paul S. , Pearse Ian S. , Cannon Charles H.
Published: April 2019

The eastern North American white oaks, a complex of approximately 16 potentially interbreeding species, have become a classic model for studying the genetic nature of species in a syngameon. Genetic work over the past two decades has demonstrated the reality of oak species, but gene flow between sympatric oaks raises the question of whether there are conserved regions of the genome that define oak species. Does gene flow homogenize the entire genome? Do the regions of the genome that distinguish a species in one part of its range differ from the regions that distinguish it in other parts of its range, where it grows in sympatry with different species? Or are there regions of the genome that are relatively conserved across species ranges? In this study, we revisit seven species of the eastern North American white oak syngameon using a set of 80 SNPs selected in a previous study because they show differences among, and consistency within, the species. We test the hypothesis that there exist segments of the genome that do not become homogenized by repeated introgression, but retain distinct alleles characteristic of each species. We undertake a rangewide sampling to investigate whether SNPs that appeared to be fixed based on a relatively small sample in our previous work are fixed or nearly fixed across the range of the species. Each of the seven species remains genetically distinct across its range, given our diagnostic set of markers, with relatively few individuals exhibiting admixture of multiple species. SNPs map back to all 12Quercuslinkage groups (chromosomes) and are separated from each other by an average of 7.47 million base pairs (± 8.74 million bp, s.d.), but are significantly clustered relative to a random null distribution, suggesting that our SNP toolkit reflects genome-wide patterns of divergence while potentially being concentrated in regions of the genome that reflect a higher-than-average history of among-species divergence. This application of a DNA toolkit designed for the simple problem of identifying species in the field has an important implication: the eastern North American white oak syngameon is composed of entities that most taxonomists would consider “good species,” and species in the syngameon retain their genetic cohesion because characteristic portions of the genome do not become homogenized despite a history of introgression.
Single-molecule analysis reveals the rapid effect of estradiol on the surface movement of AMPAR in live neurons
Authors: Godó Soma , Barabás Klaudia , Lengyel Ferenc , Ernszt Dávid , Kovács Tamás , Kecskés Miklós , Varga Csaba , Jánosi Tibor Z. , Kovács Gergely , Orsolits Barbara , Fujiwara Takahiro , Kusumi Akihiro , Ábrahám István M.
Published: April 2019

The gonadal steroid 17β-estradiol (E2) rapidly alters glutamatergic neurotransmission, but its direct effect on the AMPA receptor (AMPAR) remains unknown. Live-cell single-molecule imaging experiments revealed that E2 rapidly and dose-dependently alters the surface movement of AMPAR via membrane estrogen receptors with distinct effects on somas and neurites. The effect of E2 on the surface mobility of AMPAR depends on the integrity of the cortical actin network.
Hematological and Neurological Expressed 1 (HN1): a predictive and pharmacodynamic biomarker of metformin response in endometrial cancers
Authors: Bateman Nicholas W. , Teng Pang-ning , Hope Erica , Hood Brian L. , Oliver Julie , Ao Wei , Zhou Ming , Wang Guisong , Tommarello Domenic , Wilson Katlin , Conrads Kelly A. , Hamilton Chad A. , Darcy Kathleen M. , Casablanca Yovanni , Maxwell G. Larry , Bae-Jump Victoria , Conrads Thomas P.
Published: April 2019

Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin (mTOR) pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre- and post-metformin treated tumor tissues from a recently completed phase 0 window trial of metformin in EEC patients (ClinicalTrials.gov:NCT01911247), were analyzed by mass spectrometry (MS)-based proteomic and immunohistochemical analyses. Hematological and neurological expressed 1 (HN1) was significantly elevated in metformin responders (n=13) versus non-responders (n=7), which was also found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for HN1. Metformin response and loss of HN1 was assessed in RL95-2 and ACI-181 endometrial cancer cell lines. We further identified that silencing of HN1 abundance does not alter cellular response to metformin or basal cell proliferation, but that HN1 abundance does decrease in response to metformin treatment in RL95-2 and ACI-181 endometrial cancer cell lines. These data suggest that HN1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable pre-operative EEC patient stratification to metformin treatment and the ability to monitor patient response.

Novelty and Impact

Hematological and Neurological Expressed 1 (HN1) is elevated in endometrioid endometrial cancer (EEC) patients that respond to metformin vs non-responders and decreases after treatment. HN1 decreases after metformin treatment of EEC cells in vitro, but is not necessary for metformin response or proliferation. We report HN1 as a novel predictive and pharmacodynamic biomarker of metformin response in EEC that may enable pre-operative EEC patient stratification to metformin treatment and the ability to monitor patient response.
Modeling unitary fields and the single-neuron contribution to local field potentials in the hippocampus
Authors: Teleńczuk Maria , Teleńczuk Bartosz , Destexhe Alain
Published: April 2019

Synaptic currents represent a major contribution to the local field potential (LFP) in brain tissue, but the respective contribution of excitatory and inhibitory synapses is not known. Here, we provide estimates of this contribution by using computational models of hippocampal pyramidal neurons, constrained by in vitro recordings. We focus on the unitary LFP (uLFP) generated by single neurons in the CA3 region of the hippocampus. We first reproduce experimental results for hippocampal basket cells, and in particular how inhibitory uLFP are distributed within hippocampal layers. Next, we calculate the uLFP generated by pyramidal neurons, using morphologically-reconstructed CA3 pyramidal cells. The model shows that the excitatory uLFP is of small amplitude, smaller than inhibitory uLFPs. Indeed, when the two are simulated together, inhibitory uLFPs mask excitatory uLFPs, which might create the illusion that the inhibitory field is generated by pyramidal cells. These results provide an explanation for the observation that excitatory and inhibitory uLFPs are of the same polarity, in vivo and in vitro. These results also show that somatic inhibitory currents are large contributors of the LFP, which is important information to interpret this signal. Finally, the results of our model might form the basis of a simple method to compute the LFP, which could be applied to point neurons for each cell type, thus providing a simple biologically-grounded method to calculate LFPs from neural networks.
Image3C: a multimodal image-based and label independent integrative method for single-cell analysis
Authors: Accorsi Alice , Box Andrew C. , Peuß Robert , Wood Christopher , Alvarado Alejandro Sánchez , Rohner Nicolas
Published: April 2019

Image-based cell classification has become a common tool to identify phenotypic changes in cell populations. However, this methodology is limited to organisms possessing well characterized species-specific reagents (e.g., antibodies) that allow cell identification, clustering and convolutional neural network (CNN) training. In the absence of such reagents, the power of image-based classification has remained mostly off-limits to many research organisms. We have developed an image-based classification methodology we named Image3C (Image-Cytometry Cell Classification) that does not require species-specific reagents nor pre-existing knowledge about the sample. Image3C combines image-based flow cytometry with an unbiased, high-throughput cell cluster pipeline and CNN integration. Image3C exploits intrinsic cellular features and non-species-specific dyes to perform de novo cell composition analysis and to detect changes in cellular composition between different conditions. Therefore, Image3C expands the use of imaged-based analyses of cell population composition to research organisms in which detailed cellular phenotypes are unknown or for which species-specific reagents are not available.

Impact statement

Image3C analyzes cell populations through image-based clustering and neural network training, which allows single-cell analysis in research organisms devoid of species-specific reagents or pre-existing knowledge on cell phenotypes.
Suction feeding performance and prey escape response interact to determine feeding success in larval fish
Authors: Sommerfeld Noam , Holzman Roi
Published: April 2019

The survival of larval marine fishes during early development is strongly dependent on their ability to capture prey. Most larval fish capture prey by expanding their mouth cavity, generating a “suction flow” that draws the prey into their mouth. Larval fish dwell in a hydrodynamic regime of low Reynolds numbers, which has been shown to impede their ability to capture non-evasive prey. However, the marine environment is characterized by an abundance of evasive prey such as Copepods. These organisms can sense the hydrodynamic disturbance created by approaching predators and perform high-acceleration escape maneuvers. Using a 3D high-speed video system, we characterized the interaction between 8-33 day post hatchingSparus auratalarvae and prey from a natural zooplankton assemblage that contained evasive prey, and assessed the factors that determine the outcome of these interactions. Larvae showed strong selectivity for large prey that was moving prior to the initialization of the strike. As previously shown in studies with non-evasive prey, larval feeding success increased with increasing Reynolds numbers. However, larval feeding success was also strongly dependent on the prey’s escape response. Feeding success was lower for larger, more evasive prey, indicating that larvae might be challenged in capturing their preferred prey. The kinematics of successful strikes resulted in shorter response time but higher hydrodynamic signature available for the prey. Thus, despite being “noisier”, successful strikes on evasive prey depended on preceding the prey’s escape response. Our results show that larval performance, rather than larval preferences, determines their diet during early development.
Evidence for a multi-level trophic organization of the human gut microbiome
Authors: Wang Tong , Goyal Akshit , Dubinkina Veronika , Maslov Sergei
Published: April 2019

The human gut microbiome is a complex ecosystem, in which hundreds of microbial species and metabolites coexist, in part due to an extensive network of cross-feeding interactions. However, both the large-scale trophic organization of this ecosystem, and its effects on the underlying metabolic flow, remain unexplored. Here, using a simplified model, we provide quantitative support for a multi-level trophic organization of the human gut microbiome, where microbes consume and secrete metabolites in multiple iterative steps. Using a manually-curated set of metabolic interactions between microbes, our model suggests about four trophic levels, each characterized by a high level-to-level metabolic transfer of byproducts. It also quantitatively predicts the typical metabolic environment of the gut (fecal metabolome) in approximate agreement with the real data. To understand the consequences of this trophic organization, we quantify the metabolic flow and biomass distribution, and explore patterns of microbial and metabolic diversity in different levels. The hierarchical trophic organization suggested by our model can help mechanistically establish causal links between the abundances of microbes and metabolites in the human gut.
Growth and selection of the cyanobacterium Synechococcus sp. PCC 7002 using alternative nitrogen and phosphorus sources
Authors: Selão Tiago Toscano , Włodarczyk Artur , Nixon Peter J. , Norling Birgitta
Published: April 2019

Cyanobacteria, such as Synechococcus sp. PCC 7002 (Syn7002), are promising chassis strains for “green” biotechnological applications as they can be grown in seawater using oxygenic photosynthesis to fix carbon dioxide into biomass. Their other major nutritional requirements for efficient growth are sources of nitrogen (N) and phosphorus (P). As these organisms are more economically cultivated in outdoor open systems, there is a need to develop cost-effective approaches to prevent the growth of contaminating organisms, especially as the use of antibiotic selection markers is neither economically feasible nor ecologically desirable due to the risk of horizontal gene transfer. Here we have introduced a synthetic melamine degradation pathway into Syn7002 and evolved the resulting strain to efficiently use the nitrogen-rich xenobiotic compound melamine as the sole N source. We also show that expression of phosphite dehydrogenase in the absence of its cognate phosphite transporter permits growth of Syn7002 on phosphite and can be used as a selectable marker in Syn7002. We combined these two strategies to generate a strain that can grow on melamine and phosphite as sole N and P sources, respectively. This strain is able to resist deliberate contamination in large excess and should be a useful chassis for metabolic engineering and biotechnological applications using cyanobacteria.
Stimulation of cardiac fibroblast Piezo1 channels opposes myofibroblast differentiation and induces IL-6 secretion via Ca2+-mediated p38 MAP kinase activation
Authors: Blythe Nicola M. , Stylianidis Vasili , Ludlow Melanie J. , Gilbert Hamish T. J. , Evans Elizabeth L. , Cuthbertson Kevin , Foster Richard , Swift Joe , Li Jing , Drinkhill Mark J. , van Nieuwenhoven Frans A. , Porter Karen E. , Beech David J. , Turner Neil A.
Published: April 2019

Piezo1 is a mechanosensitive cation channel with widespread physiological importance; however its role in the heart is poorly understood. Cardiac fibroblasts are responsible for preserving the structural integrity of the myocardium and play a key role in regulating its repair and remodeling following stress or injury. We investigated expression and function of Piezo1 in cultured human and mouse cardiac fibroblasts. RT-PCR studies confirmed expression ofPiezo1mRNA in cardiac fibroblasts at similar levels to endothelial cells. Fura-2 intracellular Ca2+measurements validated Piezo1 as a functional ion channel that was activated by the Piezo1 agonist, Yoda1. Yoda1-induced Ca2+entry was inhibited by Piezo1 blockers (gadolinium, ruthenium red) and the Ca2+response was reduced proportionally by Piezo1 siRNA knockdown or in cells fromPiezo1+/−mice. Investigation of Yoda1 effects on selected remodeling genes indicated that Piezo1 activation opposed cardiac fibroblast differentiation; data confirmed by functional collagen gel contraction assays. Piezo1 activation using Yoda1 or mechanical stretch also increased the expression of interleukin-6 (IL-6), a mechanosensitive pro-hypertrophic and pro-fibrotic cytokine, in a Piezo1-dependent manner. Multiplex kinase activity profiling combined with kinase inhibitor studies and phospho-specific western blotting, established that Piezo1 activation stimulated IL-6 secretion via a pathway involving p38 MAP kinase, downstream of Ca2+entry. In summary, this study reveals that cardiac fibroblasts express functional Piezo1 channels coupled to reduced myofibroblast activation and increased secretion of paracrine signaling molecules that can modulate cardiac remodeling.
neoANT-HILL: an integrated tool for identification of potential neoantigens
Authors: Coelho Ana Carolina M F , Fonseca André L , Martins Danilo L , da Cunha Lucas M , Lins Paulo B R , de Souza Sandro J
Published: April 2019

Cancer neoantigens have attracted great interest in immunotherapy due to their ability to elicit antitumoral immune responses. These antigens are formed due to somatic mutations in the cancer genome that result in alterations of the original protein. Although current technological advances in neoantigen identification, it remains a challenging and a large number of false-positive continue to exist. In the current work, we present neoANT-HILL, an automatized user-friendly tool that integrates several immunogenomic analysis to improve neoantigens detection from NGS data. The program input can be a file with somatic mutations called and/or RNA-seq data. Our tool was applied on somatic mutations of melanoma dataset from TCGA and found that neoANT-HILL was able to predicted potential neoantigens. The software is available on github athttps://github.com/neoanthill/neoANT-HILL.
Differential characterization of physiological and biochemical responses during drought stress in finger millet varieties
Authors: Mukami Asunta , Ngetich Alex , Mweu Cecilia , Oduor Richard O. , Muthangya Mutemi , Mbinda Wilton Mwema
Published: April 2019

Drought is the most perilous abiotic stress that affects finger millet growth and productivity worldwide. For the successful production of finger millet, selection of drought tolerant varieties is necessary and critical stages under drought stress, germination and early seedling growth, ought to be fully understood. This study investigated the physiological and biochemical responses of six finger millet varieties (GBK043137, GBK043128, GBK043124, GBK043122, GBK043094 and GBK043050) under mannitol-induced drought stress. Seeds were germinated on sterile soil and irrigated with various concentrations of mannitol (200, 400 and 600 mM) for two weeks. Comparative analysis in terms of relative water content (RWC), chlorophyll, proline, and malondialdehyde (MDA) contents were measured the physiological and biochemical characteristics of drought stress. The results showed that increased level of drought stress seriously decreased germination and early seedling growth of finger millet varieties. However, root growth was increased. In addition, exposition to drought stress triggered a significant decrease in relative water content and chlorophyll content reduction the biochemical parameters assay showed less reduction of relative water content. Furthermore, oxidative damage indicating parameters such as proline concentration and MDA content increased. Varieties GBK043137 and GBK043094 were less affected by drought as shown by significant change in the physiological parameters. Our findings reveal the difference and linkage between the physiological responses of finger millet to drought and are vital for breeding and selection of drought tolerant varieties of finger millet. Further investigations on genomic and molecular to deeply insight the detail mechanisms of drought tolerance in finger millet need to explored.
Multiplexed and Inducible Gene Modulation in Human Pluripotent Stem Cells by CRISPR Interference and Activation
Authors: Hazelbaker Dane Z. , Beccard Amanda , Mazzucato Patrizia , Angelini Gabriella , Messana Angelica , Lam Daisy , Eggan Kevin , Barrett Lindy E.
Published: April 2019

CRISPR-Cas9-mediated gene interference (CRISPRi) and activation (CRISPRa) approaches hold promise for functional genomic studies and genome-wide screens in human pluripotent stem cells (hPSCs). However, in contrast to CRISPR-Cas9 nuclease approaches, the efficiency of CRISPRi/a depends on continued expression of the dead Cas9 (dCas9) effector and guide RNA (gRNA), which can vary substantially depending on transgene design and delivery. Here, we design new fluorescently labeledpiggyBac(PB) vectors to deliver robust and stable expression of multiplexed gRNAs. In addition, we generate hPSC lines harboring AAVS1-integrated, inducible and fluorescent dCas9-KRAB and dCas9-VPR transgenes to allow for accurate quantification and tracking of cells that express both the dCas9 effectors and gRNAs. We then employ these systems to target theTCF4gene and conduct a rigorous assessment of expression levels of the dCas9 effectors, gRNAs and targeted gene. Collectively, these data provide proof-of-principle application of a stable, multiplexed PB gRNA delivery system that can be widely exploited to further enable genome engineering studies in hPSCs. Paired with diverse CRISPR tools including our dual fluorescence CRISPRi/a cell lines, this system would facilitate functional dissection of individual genes and pathways as well as larger-scale screens for studies of development and disease.
Reliability, sensitivity and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors
Authors: Kolskår Knut K. , Richard Geneviève , Alnæs Dag , Dørum Erlend S. , Sanders Anne-Marthe , Ulrichsen Kristine M. , Sánchez Jennifer Monereo , Ihle-Hansen Hege , Nordvik Jan E. , Westlye Lars T.
Published: April 2019

Computerized cognitive training (CCT) combined with transcranial direct current stimulation (tDCS) has showed some promise in alleviating cognitive impairments in patients with brain disorders, but the robustness and possible mechanisms are unclear. In this prospective double-blind randomized clinical trial, we investigated the feasibility and effectiveness of combining CCT and tDCS, and tested the predictive value of and training-related changes in fMRI-based brain activation during attentive performance (multiple object tracking) obtained at inclusion, before initiating training, and after the three-weeks intervention in chronic stroke patients (> 6 months since hospital admission). Patients were randomized to one of two groups, receiving CCT and either (1) tDCS targeting left dorsolateral prefrontal cortex (1 mA), or (2) sham tDCS, with 40s active stimulation (1 mA) before fade out of the current. 77 patients were enrolled in the study, 54 completed the cognitive training, and 48 completed all training and MRI sessions. We found significant improvement in performance across all trained tasks, but no additional gain of tDCS. fMRI-based brain activation showed high reliability, and higher cognitive performance was associated with increased tracking-related activation in the dorsal attention network (DAN) and default mode network (DMN) as well as anterior cingulate after compared to before the intervention. We found no significant associations between cognitive gain and brain activation measured before training or in the difference in activation after intervention. Combined, these results show significant training effects on trained cognitive tasks in stroke survivors, with no clear evidence of additional gain of concurrent tDCS.
Augmenting Quadriplegic Hand Function Using a Sensorimotor Demultiplexing Neural Interface
Authors: Ganzer PD , Colachis SC , Schwemmer MA , Friedenberg DA , Swiftney CE , Jacobowitz AF , Weber DJ , Bockbrader MA , Sharma G
Published: April 2019

Background

The sense of touch is a key component of motor function. Severe spinal cord injury (SCI) should essentially eliminate sensory information transmission to the brain, that originates from skin innervated from below the lesion. We assessed the hypothesis that, following SCI, residual hand sensory information is transmitted to the brain, can be decoded amongst competing sensorimotor signals, and used to enhance the sense of touch via an intracortically controlled closed-loop brain-computer interface (BCI) system.

Methods

Experiments were performed with a participant who has an AIS-A C5 SCI and an intracortical recording array implanted in left primary motor cortex (M1). Sensory stimulation and standard clinical sensorimotor functional assessments were used throughout a series of several mechanistic experiments.

Findings

Our results demonstrate that residual afferent hand sensory signals surprisingly reach human primary motor cortex and can be simultaneously demultiplexed from ongoing efferent motor intention, enabling closed-loop sensory feedback during brain-computer interface (BCI) operation. The closed-loop sensory feedback system was able to detect residual sensory signals from up to the C8 spinal level. Using the closed-loop sensory feedback system enabled significantly enhanced object touch detection, sense of agency, movement speed, and other sensorimotor functions.

Interpretation

To our knowledge, this is the first demonstration of simultaneously decoding multiplexed afferent and efferent activity from human cortex to control multiple assistive devices, constituting a ‘sensorimotor demultiplexing’ BCI. Overall, our results support the hypothesis that sub-perceptual neural signals can be decoded reliably and transformed to conscious perception, significantly augmenting function.

Funding

Internal funding was provided for this study from Battelle Memorial Institute and The Ohio State University Center for Neuromodulation.
The influence of feeding behaviour and temperature on the capacity of mosquitoes to transmit malaria
Authors: Suh Eunho , Grossman Marissa K. , Waite Jessica L. , Dennington Nina L. , Sherrard-Smith Ellie , Churcher Thomas S. , Thomas Matthew B.
Published: April 2019

Insecticide-treated bed nets reduce malaria transmission by limiting contact between mosquito vectors and human hosts when mosquitoes feed during the night. However, malaria vectors can also feed in the early evening and in the morning when people are not protected. Here, we explored how timing of blood feeding interacts with environmental temperature to influence the capacity of Anopheles mosquitoes to transmit the human malaria parasite, Plasmodium falciparum. We found no effect of biting time itself on the proportion of mosquitoes that became infectious (vector competence) at constant temperature. However, when mosquitoes were maintained under more realistic fluctuating temperatures there was a significant increase in competence for mosquitoes feeding in the evening, and a significant reduction in competence for those feeding in the morning, relative to those feeding at midnight. These effects appear to be due to thermal sensitivity of malaria parasites during the initial stages of parasite development within the mosquito, and the fact that mosquitoes feeding in the evening experience cooling temperatures during the night, whereas mosquitoes feeding in the morning quickly experience warming temperatures that are inhibitory to parasite establishment. A transmission dynamics model illustrates that such differences in competence could have important implications for disease endemicity, the extent of transmission that persists in the presence of bed nets, and the epidemiological impact of behavioural resistance. These results indicate the interaction of temperature and feeding behaviour to be a major ecological determinant of the vectorial capacity of malaria mosquitoes.
Rapid Generation of Medical Countermeasure Candidates Via Computational Variation Analysis
Authors: Ricke Darrell O.
Published: April 2019

Rapid responses to emerging infectious diseases are needed for viral and bacterial pathogens. For some pathogens, no medical countermeasures (MCMs) yet exist. Pathogen heterogeneity and antigenic variation lead to immune response escape mutations for some pathogens (e.g., influenza) limiting the effectiveness of medical countermeasures. High throughput sequencing enables characterization of large numbers of pathogen isolates to which residue variation analysis can be applied to identify low variability targets. Multiple approaches are proposed that leverage these low variability targets as the first step of medical countermeasure development. Classes of MCMs informed by this approach include the following: DNA or RNA vaccines, both B-cell and T-cell vaccination strategies, anti-viral RNA targeting, antibody therapeutics, and aptamer targeting of viral protein complex interfaces as potential treatment strategies for infected individuals. Variation analysis-designed countermeasures targeting the Ebola glycoprotein are presented to illustrate the concepts for the proposed multiple targeted countermeasures.
A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development
Authors: Basisty Nathan , Kale Abhijit , Jeon Okhee H , Kuehnemann Chisaka , Payne Therese , Rao Chirag , Holtz Anja , Shah Samah , Sharma Vagisha , Ferrucci Luigi , Campisi Judith , Schilling Birgit
Published: April 2019

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of, and promising therapeutic target for, multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the ‘SASP Atlas’, a comprehensive proteomic database of soluble and exosome SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins, but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including GDF15, STC1 and SERPINs, which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging. Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus and tissue of origin of senescent cells in vivo.

Abbreviations

ATV, atazanavir treatment; BLSA, Baltimore Longitudinal Study of Aging; CTL, control; DDA, data-dependent acquisition; DAMP, damage-associated molecular pattern; DIA, data-independent acquisition; eSASP, extracellular vesicle senescence associated secretory phenotype; EVs, extracellular vesicles; IR, X-irradiation; MS, mass spectrometry; RAS, inducible RAS overexpression; SA-β-Gal, senescence-associated β-galactosidase; SEN, senescent; sSASP, soluble senescence associated secretory phenotype.
EM-LDDMM for 3D to 2D registration
Authors: Tward Daniel , Miller Michael
Published: April 2019

We examine the problem of mapping dense 3D atlases onto censored, sparsely sampled 2D target sections at micron and meso scales. We introduce a new class of large deformation diffeomorphic metric mapping (LD-DMM) algorithms for generating dense atlas correspondences onto sparse 2D samples by introducing a field of hidden variables which must be estimated representing a large class of target image uncertainties including (i) unknown parameters representing cross stain contrasts, (ii) censoring of tissue due to localized measurements of target subvolumes and (iii) sparse sampling of target tissue sections. For prediction of the hidden fields we introduce the generalized expectation-maximization algorithm (EM) for which the E-step calculates the conditional mean of the hidden variates simultaneously combined with the diffeomorphic correspondences between atlas and target coordinate systems. The algorithm is run to fixed points guaranteeing estimators satisfy the necessary maximizer conditions when interpreted as likelihood estimators. The dense mapping is an injective correspondence to the sparse targets implying all of the 3D variations are performed only on the atlas side with variation in the targets only 2D manipulations.
The power of model-to-crop translation illustrated by reducing seed loss from pod shatter in oilseed rape
Authors: Stephenson Pauline , Stacey Nicola , Brüser Marie , Pullen Nick , Ilyas Muhammad , O’Neill Carmel , Wells Rachel , Østergaard Lars
Published: April 2019

In the 1980s, plant scientists descended on a small weedArabidopsis thaliana(thale cress) and developed it into a powerful model system to study plant biology. The massive advances in genetics and genomics since then has allowed us to obtain incredibly detailed knowledge on specific biological processes of Arabidopsis growth and development, its genome sequence and the function of many of the individual genes. This wealth of information provides immense potential for translation into crops to improve their performance and address issues of global importance such as food security. Here we describe how fundamental insight into the genetic mechanism by which seed dispersal occurs in members of the Brassicaceae family can be exploited to reduce seed loss in oilseed rape (Brassica napus). We demonstrate that by exploiting data on gene function in model species, it is possible to adjust the pod-opening process in oilseed rape thereby significantly increasing yield. Specifically, we identified mutations in multiple paralogues of theINDEHISCENTandGA4genes inB. napusand have overcome genetic redundancy by combining mutant alleles. Finally, we present novel software for the analysis of pod shatter data that is applicable to any crop for which seed dispersal is a serious problem. These findings highlight the tremendous potential of fundamental research in guiding strategies for crop improvement.

Keymessage

Elucidation of key regulators inArabidopsisfruit patterning has facilitated knowledge-translation into crop species to address yield loss caused by premature seed dispersal (pod shatter).
Emergence of Novel Lineage of Foot-and-Mouth Disease Virus Serotype Asia1 BD-18 (G-IX) in Bangladesh
Authors: Ali M. Rahmat , Alam A. S. M. R. U. , Amin M. Al , Siddique Mohammad A. , Sultana Munawar , Hossain M. Anwar
Published: April 2019

In 2018, a novel circulatory foot-and-mouth disease virus serotype Asia1 BD-18 (G-IX) lineage containing a unique mutation has emerged in Bangladesh. This emergence may be following the evolutionary roadmap of previously reported lineage. Inappropriate vaccination and inefficient outbreak surveillance possibly contributed to the current episode of emergence.
Diagnostic value of chest ultrasound in children with cystic fibrosis
Authors: Strzelczuk-Judka Lidia , Wojsyk-Banaszak Irena , Zakrzewska Aleksandra , Jonczyk-Potoczna Katarzyna
Published: April 2019

Cystic fibrosis (CF) is one of the most common genetic disorders in the Caucasian population. The disease has a progressive course and leads to reduced life quality and life expectancy. Standard diagnostic procedures used in the monitoring of CF patients, include methods exposing patients to the ionizing radiation. With increasing life expectancy in CF the cumulative dose of ionising radiation increases, prompting clinicians’ search for safer imaging studies. Despite its safety and availability lung ultrasound (LUS) is not routinely used in the diagnostic evaluation of CF patients.

The aim of the study was to evaluate the diagnostic value of LUS in children with CF compared to chest X-ray, and to assess the diagnostic value of the recently developed LUS score - CF-USS (Cystic Fibrosis Ultrasound Score).

LUS was performed in 48 CF children aged from 5 to 18 years (24 girls and 24 boys). LUS consisted in the assessment of the pleura, lung sliding, A-line and B-line artifacts, “lung rockets”, alveolar consolidations, air bronchogram and pleural effusion. Chest radiography was performed in all patients and analyzed according to the modified Chrispin-Norman score. LUS was analyzed according to CF-USS.

Correlation between the CF-USS and the modified Chrispin-Norman scores were moderate (R=0.52, p=0.0002) and strong in control studies. In 75% of patients undergoing LUS, small areas of subpleural consolidations were observed, not visible on X-rays. At the same time, LUS was not sensitive enough to visualize bronchial pathology, which plays an important role in assessing the disease progression.

Conclusions

LUS constitutes an invaluable tool for the diagnosis of subpleural consolidations. CF-USS results correlate with conventional x-ray modified Chrispin–Norman score. LUS should be considered an accessory radiographic examination in the monitoring of CF patients, and CF-USS may provide clinicians with valuable information concerning the disease progression.
Characterization of a new cytorhabdovirus discovered in papaya (Carica papaya) plantings of Ecuador and its relationship with a bean-infecting strain from Brazil
Authors: Medina-Salguero Andres X. , Cornejo-Franco Juan F. , Grinstead Samuel , Mollov Dimitre , Mowery Joseph D. , Flores Francisco , Quito-Avila Diego F.
Published: April 2019

The complete genome of a new rhabdovirus infecting papaya (Carica papayaL.) was sequenced and characterized. The genome consists of 13,469 nucleotides with six canonical open reading frames (ORFs) predicted from the antigenomic strand. In addition, two overlapping short ORFs were predicted between ORFs 3 and 4. Phylogenetic analyses using amino acid sequences from the nucleocapsid, glycoprotein and polymerase, grouped the virus with members of the genusCytorhabdovirus, with rice stripe mosaic virus, yerba mate chlorosis-associated virus and Colocasia bobone disease-associated virus as closest relatives. The 3’ leader and 5’ trailer sequences were 144 and 167 nt long, respectively. Each end contains complementary sequences prone to form panhandle structures. The motif 3’-AUUCUUUUUG-5’, conserved across rhabdoviruses, was identified in all but one intergenic regions; whereas the motif 3’-ACAAAAACACA-5’ was found in three intergenic junctions. This is the first complete genome of a cytorhabdovirus infecting papaya. The virus was prevalent in commercial plantings of Los Ríos, the most important papaya producing province of Ecuador. During the final stage of this manuscript preparation, the genome of a bean-associated cytorhabdovirus became available. Nucleotide identity (97%) between both genomes indicated that the two viruses are strains of the same species, for which we propose the name papaya cytorhabdovirus E.
The transformation matrices (distortion, orientation, correspondence), their continuous forms and their variants
Authors: Cayron Cyril
Published: April 2019

The crystallography of displacive/martensitic phase transformations can be described with three types of matrix: the lattice distortion matrix, the orientation relationship matrix and the correspondence matrix. Given here are some formulae to express them in crystallographic, orthonormal and reciprocal bases, and an explanation is offered of how to deduce the matrices of inverse transformation. In the case of the hard-sphere assumption, a continuous form of distortion matrix can be determined, and its derivative is identified to the velocity gradient used in continuum mechanics. The distortion, orientation and correspondence variants are determined by coset decomposition with intersection groups that depend on the point groups of the phases and on the type of transformation matrix. The stretch variants required in the phenomenological theory of martensitic transformation should be distinguished from the correspondence variants. The orientation and correspondence variants are also different; they are defined from the geometric symmetries and algebraic symmetries, respectively. The concept of orientation (ir)reversibility during thermal cycling is briefly and partially treated by generalizing the orientation variants with n-cosets and graphs. Some simple examples are given to show that there is no general relation between the numbers of distortion, orientation and correspondence variants, and to illustrate the concept of orientation variants formed by thermal cycling.
Social-cognitive antecedents of new venture internationalization
Authors: Wasowska Aleksandra
Published: April 2019

Purpose

The purpose of this paper is to investigate the social-cognitive antecedents of an entrepreneur’s internationalization intent and a firm’s behavior. Building on the insights of social-cognitive psychology, the author develops a conceptual model linking an entrepreneur’s positive orientation, self-efficacy beliefs, internationalization intent and actual behavior of the firm.

Design/methodology/approach

The author tests this model with a sample of 310 Polish firms (including 241 domestic and 69 international new ventures), drawing on data collected first in 2006 and then in 2007.

Findings

The author finds that self-efficacy mediates between positive orientation and internationalization intent, and that an entrepreneur’s internationalization intent predicts a firm’s behavior (i.e. foreign market entry). Moreover, firm age moderates the relationship between an entrepreneur’s positive orientation and internationalization propensity among new ventures.

Research limitations/implications

Overall, the findings demonstrate that social-cognitive theory is useful in predicting new venture internationalization.

Practical implications

Based on the findings, the author recommends that managerial education in international management combines the development of “formal” skills and cross-cultural competencies with experiential and vicarious learning.

Originality/value

The study combines insights from psychology and international business, thus responding to numerous calls for a more interdisciplinary and cognition-oriented focus on the international behavior of firms.
Cost-optimal as a tool for helping in designing distribution transformer using particle swarm optimization
Authors: Jarrahi Mohammad Amin , Roshandel Emad , Allahbakhshi Mehdi , Ahmadi Mohammad
Published: April 2019

Purpose

This paper aims to achieve an optimal design for distribution transformers considering cost and power losses. Particle swarm optimization (PSO) algorithm is used as an optimization tool for minimizing the objective functions of design procedure which are cost and electrical and iron losses.

Design/methodology/approach

In this paper, distribution transformer losses are considered as operating costs. Also, transformer construction cost which depends on the amount of iron and copper in the structure is assumed as its initial cost. In addition, some other important constraints such as appropriate ranges of transformer efficiency, voltage regulation, temperature rise, no-load current, and winding fill factor are investigated in the design procedure. The PSO algorithm is applied to find optimum amount of needed copper and iron for a typical distribution transformer. Moreover, transformer impedance considered as a constraint to achieve an acceptable voltage regulation in the design process.

Findings

It is shown that the proposed design procedure provides a simple and effective approach to estimate the flux and current densities for minimizing the active part cost and active power losses which means reduction in amount of transformer total owning cost (TOC).

Originality/value

The methodology advances a proposal for reducing distribution transformers costs using PSO algorithm. The approach considers the aforementioned constraints and TOC to minimize the active part cost and maximize the efficiency. It is demonstrated that a designed transformer will not be optimum when the transformer losses over years are not considered in design procedure. Finally, the results prove the effectiveness of the proposed procedure in designing cost-effective distribution transformers from its initial cost until its whole life.