bluuebunny/crossref_metadata_2025 huggingface dataset:
External quality assessment of bacterial identification and antimicrobial susceptibility testing in African national public health laboratories, 2011–2016
Authors: Perovic Olga , Yahaya Ali A. , Viljoen Crystal , Ndihokubwayo Jean-Bosco , Smith Marshagne , Coulibaly Sheick O. , De Gouveia Linda , Oxenford Christopher J. , Cognat Sebastien , Frean John
Published: August 2019

Background

In 2002, the World Health Organization (WHO) launched a regional microbiology external quality assessment (EQA) programme for national public health laboratories in the African region, initially targeting priority epidemic-prone bacterial diseases, and later including other common bacterial pathogens.

Objectives

The aim of this study was to analyse the efficacy of an EQA programme as a laboratory quality system evaluation tool.

Methods

We analysed the proficiency of laboratories’ performance of bacterial identification and AST for the period 2011–2016. Overall, 81 laboratories from 45 countries participated.

The National Institute for Communicable Diseases of South Africa provided technical coordination following an agreement with WHO, and supplied EQA samples of selected bacterial organisms for microscopy (Gram stain), identification, and antimicrobial susceptibility testing (AST). National public health laboratories, as well as laboratories involved in the Invasive Bacterial Diseases Surveillance Network, were enrolled by the WHO Regional Office for Africa to participate in the EQA programme.

Results

We analysed participants’ results of 41 surveys, which included the following organisms sent as challenges: Streptococcus pneumonia, Haemophilus influenza, Neisseria meningitidis, Salmonella Typhi, Salmonella Enteritidis, Shigella flexneri, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus anginosus, Enterococcus faecium, Serratia marcescens, Acinetobacter baumannii, and Enterobacter cloacae. Overall, 76% of participants obtained acceptable scores for identification, but a substantial proportion of AST scores were not in the acceptable range.

Conclusion

In the African Region, implementation of diagnostic stewardship in clinical bacteriology is generally suboptimal. This report illustrates that AST is poorly done compared to microscopy and identification. It is critically important to make the case for implementation of quality assurance in AST, as it is the cornerstone for antimicrobial resistance surveillance reporting and implementation of the Global Antimicrobial Resistance Surveillance System.
Identification of immunoreactive linear epitopes ofBorrelia miyamotoi
Authors: Tokarz Rafal , Tagliafierro Teresa , Caciula Adrian , Mishra Nischay , Thakkar Riddhi , Chauhan Lokendra V , Sameroff Stephen , Delaney Shannon , Wormser Gary P. , Marques Adriana , Lipkin W. Ian
Published: August 2019

Borrelia miyamotoiis an emerging tick-borne spirochete transmitted byIxodidticks. Current serologic assays forB. miyamotoiare impacted by genetic similarities to otherBorreliaand limited understanding of optimal antigenic targets. In this study, we employed the TBD-Serochip, a peptide array platform, to identify new linear targets for serologic detection ofB. miyamotoi. We examined a wide range of suspectedB. miyamotoiantigens and identified 352 IgM and 91 IgG reactive peptides, with the majority mapping to variable membrane proteins. These included peptides within conserved fragments of variable membrane proteins that may have greater potential for differential diagnosis. We also identified reactive regions on FlaB, and demonstrate crossreactivity ofB. burgdorferiC6 with aB. miyamotoiC6-like peptide. The panel of linear peptides identified in this study can be used to enhance serodiagnosis ofB. miyamotoi.
Motion Coherence and Luminance Contrast Interact in Driving Visual Gamma-Band Activity
Authors: Pellegrini Franziska , Hawellek David J , Pape Anna-Antonia , Hipp Joerg F , Siegel Markus
Published: August 2019

Synchronized neuronal population activity in the gamma-frequency range (> 30 Hz) correlates with the bottom-up drive of various visual features. It has been hypothesized that gamma-band synchronization enhances the gain of neuronal representations, yet evidence remains sparse. We tested a critical prediction of the gain hypothesis, which is that features that drive synchronized gamma-band activity interact super-linearly. To test this prediction, we employed whole-head magnetencephalography (MEG) in human subjects and investigated if the strength of visual motion (motion coherence) and luminance contrast interact in driving gamma-band activity in visual cortex. We found that gamma-band activity (64 to 128 Hz) monotonically increased with coherence and contrast while lower frequency activity (8 to 32 Hz) decreased with both features. Furthermore, as predicted for a gain mechanism, we found a multiplicative interaction between motion coherence and contrast in their joint drive of gamma-band activity. The lower frequency activity did not show such an interaction. Our findings provide evidence, that gamma-band activity acts as a cortical gain mechanism that nonlinearly combines the bottom-up drive of different visual features in support of visually guided behavior.
Epigenetic mechanism of carbohydrate sulfotransferase 3 (CHST3) downregulation in the aging brain
Authors: Baidoe-Ansah David , Sadman Sakib M , Jia Shaobo , Fischer Andre , Kaushik Rahul , Dityatev Alexander
Published: August 2019

Neural extracellular matrix (ECM) is a complex molecular meshwork surrounding neurons and glial cells in the extracellular space. Structural and functional state of ECM in the brain is tightly regulated by various components of neural ECM such as hyaluronic acid, chondroitin sulfate proteoglycans, link proteins, tenascins, various matrix-modifying enzymes such as chondroitin sulfate synthases and carbohydrate sulfotransferase together with matrix-degrading enzymes. Age-dependent accumulation of ECM molecules is implicated in the age-associated decline in synaptic and cognitive functions. Understanding age-associated changes in the expression of genes involved in regulating various components of ECM can provide an insight into the role of ECM in the aging brain. Hence, in this study, we compared the expression levels of ECM regulating genes in three groups of mice: 2-3 months old mice (2-3M), 22- to 26-month-old mice (22-26M) and more than 30-month-old mice (>30M). Using qPCR, we discovered that in the hippocampus of >30M old mice, the majority of ECM related genes are downregulated, while genes related to neuroinflammation are highly upregulated. This pattern was accompanied by a decrease in cognitive performance of the >30M old mice and was most correlated among ECM-related genes with the downregulation of carbohydrate sulfotransferase 3 (CHST3) gene expression. Interestingly, in 24-26M mice, no general decrease in the expression of ECM related genes was observed, although we still found the upregulation in neuroinflammatory genes and downregulation ofCHST3. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region ofCHST3gene in non-neuronal (NeuN-negative) but not in neuronal (NeuN-positive) cells. We conclude that in 22-26 M old brains there are minor changes in expression of the studiedbona fideneural ECM genes but there is a prominent epigenetic dysregulation of theCHST3gene responsible for 6-sulfation of chondroitin sulfates, which may lead to impaired brain plasticity and cognitive decline.
Staging Alzheimer’s disease in the brain and retina of B6.APP/PS1 mice by transcriptional profiling
Authors: Chintapaludi Sumana R. , Uyar Asli , Jackson Harriet M. , Acklin Casey J. , Wang Xulong , Sasner Michael , Carter Gregory W. , Howell Gareth R.
Published: August 2019

Alzheimer’s disease (AD) is a common form of dementia characterized by amyloid plaque deposition, TAU pathology, neuroinflammation and neurodegeneration. Mouse models recapitulate some key features of AD. For instance, the B6.APP/PS1 model (carrying human transgenes for mutant forms of APP and PSEN1) shows plaque deposition and associated neuroinflammatory responses involving both astrocytes and microglia beginning around 6 months of age. However, in our colony, TAU pathology, significant neurodegeneration and cognitive decline are not apparent in this model even at older ages. Therefore, this model is ideal for studying neuroinflammatory responses to amyloid deposition. Here, RNA sequencing of brain and retinal tissue, generalized linear modeling (GLM), functional annotation followed by validation by immunofluorescence (IF) was performed in B6.APP/PS1 mice to determine the earliest molecular changes prior to and around the onset of plaque deposition (2-6 months of age). Multiple pathways were shown to be activated in response to amyloid deposition including the JAK/STAT and NALFD pathways. Putative, cell-specific targets of STAT3, a central component of the JAK/STAT pathway, were identified that we propose provide more precise options for assessing the potential for targeting activation of the JAK/STAT pathway as a treatment for human AD. In the retina, GLM predicted activation of vascular-related pathways. However, many of the gene expression changes comparing B6 with B6.APP/PS1 retina samples occurred prior to plaque onset (2 months of age). This suggests retinal changes in B6.APP/PS1 mice may be an artefact of overexpression of mutant forms of APP and PSEN1 providing limited translatability to human AD. Therefore, caution should be taken when using this mouse model to assess the potential of using the eye as a window to the brain for AD.
Chromatin 3D structure reconstruction with consideration of adjacency relationship among genomic loci
Authors: Li Fang-Zhen , Liu Zhi-E , Li Xiu-Yuan , Bu Li-Mei , Bu Hong-Xia , Liu Hui , Zhang Cai-Ming
Published: August 2019

Chromatin 3D conformation plays important roles in regulating gene or protein functions. High-throughout chromosome conformation capture (3C)-based technologies, such as Hi-C, have been exploited to acquire the contact frequencies among genomic loci at genome-scale. Various computational tools have been proposed to recover the underlying chromatin 3D structures from in situ Hi-C contact map data. As connected residuals in a polymer, neighboring genomic loci have intrinsic mutual dependencies in building a 3D conformation. However, current methods seldom take this feature into account. We present a method called ShNeigh, which combines the classical MDS technique with local dependence of neighboring loci modelled by a Gaussian formula, to infer the best 3D structure from noisy and incomplete contact frequency matrices. The results obtained on simulations and real Hi-C data showed, while keeping the high-speed nature of classical MDS, ShNeigh is more accurate and robust than existing methods, especially for sparse contact maps. A Matlab implementation of the proposed method is available at https://github.com/fangzhen-li/ShNeigh.

Author summary

We propose a new method to infer a consensus 3D genome structure from a Hi-C contact map. The novelty of our method is that it takes into accounts the adjacency of genomic loci along chromosomes. Specifically, the proposed method penalizes the optimization problem of the classical multidimensional scaling method with a smoothness constraint weighted by a function of the genomic distance between the pairs of genomic loci. We demonstrate this optimization problem can still be solved efficiently by a classical multidimensional scaling method. We then show that the method can recover stable structures in high noise settings. We also show that it can reconstruct similar structures from data obtained using different restriction enzymes.
Housing laboratory mice deficient for Nod2 and Atg16l1 in a natural environment uncovers genetic and environmental contributions to immune variation
Authors: Lin Jian-Da , Devlin Joseph C. , Yeung Frank , McCauley Caroline , Leung Jacqueline M. , Chen Ying-Han , Cronkite Alex , Hansen Christina , Drake-Dunn Charlotte , Ruggles Kelly V. , Cadwell Ken , Graham Andrea L. , Loke P’ng
Published: August 2019

The relative contributions of genetic and environmental factors to variation in immune responses are still poorly understood. Here, we performed a deep phenotypic analysis of immunological parameters of laboratory mice released into an outdoor enclosure, carrying susceptibility genes (Nod2 and Atg16l1) implicated in the development of inflammatory bowel diseases. Variations of immune cell populations were largely driven by environment, whereas cytokine production in response to stimulation was affected more by genetic mutations. Multi-omic models identified transcriptional signatures associated with differences in T cell populations. Subnetworks associated with responses against Clostridium perfringens, Candida albicans and Bacteroides vulgatus were also coupled with rewilding. Hence, exposing laboratory mice carrying different genetic mutations to a natural environment uncovered important contributors to immune variation.

One sentence summary

Natural environment exposure in laboratory mice primarily promotes variation in population frequencies of immune cells, whereas cytokine responses to stimulation are affected more by genetic susceptibility to inflammatory bowel disease.
Predicting 30-day Hospital Readmissions Using Artificial Neural Networks with Medical Code Embedding
Authors: Liu Wenshuo , Singh Karandeep , Ryan Andrew M. , Sukul Devraj , Mahmoudi Elham , Waljee Akbar K. , Stansbury Cooper M. , Zhu Ji , Nallamothu Brahmajee K.
Published: August 2019

Reducing unplanned readmissions is a major focus of current hospital quality efforts. In order to avoid unfair penalization, administrators and policymakers use prediction models to adjust for the performance of hospitals from healthcare claims data. Regression-based models are a commonly utilized method for such risk-standardization across hospitals; however, these models often suffer in accuracy. In this study we, compare four prediction models for unplanned patient readmission for patients hospitalized with acute myocardial infarction (AMI), congestive health failure (HF), and pneumonia (PNA) within the Nationwide Readmissions Database in 2014. We evaluated hierarchical logistic regression and compared its performance with gradient boosting and two models that utilize artificial neural network. We show that unsupervised Global Vector for Word Representations embedding representations of administrative claims data combined with artificial neural network classification models significantly improves prediction of 30-day readmission. Our best models increased the AUC for prediction of 30-day readmissions from 0.68 to 0.72 for AMI, 0.60 to 0.64 for HF, and 0.63 to 0.68 for PNA compared to hierarchical logistic regression. Furthermore, risk-standardized hospital readmission rates calculated from our artificial neural network model that employed embeddings led to reclassification of approximately 10% of hospitals across categories of hospital performance. This finding suggests that prediction models that incorporate new methods classify hospitals differently than traditional regression-based approaches and that their role in assessing hospital performance warrants further investigation.
Diffuse Reflectance Spectroscopy reveals heat stress-induced changes in hemoglobin profile in chicken breast
Authors: Dadgar Sina , Greene Liz , Dhamad Ahmed , Mallmann Barbara , Dridi Sami , Rajaram Narasimhan
Published: August 2019

Global rise in incidence of woody breast (WB) syndrome imposes a significant economic burden on the poultry industry. The increase in WB is due to the large increase in the weight of chickens these days within a very short period. An early determination of WB can significantly reduce losses to the poultry industry. Diffuse reflectance spectroscopy provides a noninvasive and rapid method to interrogate tissue function. The sensitivity of DRS to the distinct absorption spectra of oxygenated and deoxygenated hemoglobin allows accurate quantification of average hemoglobin concentration and vascular oxygenation within the sampled tissue. In this study, we used diffuse reflectance spectroscopy to monitor breast hemoglobin concentration (THb) and vascular oxygen saturation (sO2) of 16 chickens that were exposed to heat stress (HS). HS is an important cause of WB myopathy in chickens. Animals were exposed to heat-stress (HS) and optical data were acquired at three time points: at baseline prior to heat stress, 2 days, and 21 days after initiation of HS. Our results show that animals from control and HS groups had a steady decay in optically derived breast hemoglobin concentration consistent with independent i-STAT measurements made on blood sampled from the femoral artery and could provide a noninvasive technology for monitoring tissue function in the poultry industry.
First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation
Authors: Brubaker Gregory , Lorkowski Shuhui W. , Gulshan Kailash , Hazen Stanley L. , Gogonea Valentin , Smith Jonathan D.
Published: August 2019

The crystal structure of a C-terminal deletion of apolipoprotein A-I (apoA1) shows a large helical bundle structure in the amino half of the protein, from residues 8 to 115. Using site directed mutagenesis, guanidine or thermal denaturation, cell free liposome clearance, and cellular ABCA1-mediated cholesterol efflux assays, we demonstrate that apoA1 lipidation can occur when the barrier to this bundle unfolding is lowered. The absence of the C-terminus renders the bundle harder to unfold resulting in loss of apoA1 lipidation that can be reversed by point mutations, such as Trp8Ala, and by truncations as short as 8 residues in the amino terminus, both of which lower the barrier to helical bundle unfolding. Locking the bundle via a disulfide bond leads to loss of apoA1 lipidation. We propose a model in which the C-terminus acts on the N-terminus to destabilize helical bundle. Upon lipid binding to the C-terminus, Trp8 is displaced from its interaction with Phe57, Arg61, Leu64, Val67, Phe71, and Trp72 to destabilize the bundle. However, when the C-terminus is deleted, Trp8 cannot be displaced, the bundle cannot unfold, and apoA1 cannot be lipidated.
First analysis of behavioural responses of humpback whales (Megaptera novaeangliae) to two acoustic alarms in a northern feeding ground off Iceland
Authors: Basran Charla J. , Woelfing Benno , Neumann Charlotte , Rasmussen Marianne H.
Published: August 2019

Mitigating cetacean entanglement in fishing industries is of global interest. Strategies include the use of acoustic alarms to warn whales of fishing gear. For baleen whales, responses to acoustic alarms are poorly understood. This behavioural response study compared the behaviour of humpback whales (Megaptera novaeangliae) in their feeding grounds off Iceland prior to, during, and after exposure to a low-frequency whale pinger (Future Oceans) and a high-frequency seal scarer (Lofitech ltd.). Linear mixed effects models and binary generalized linear mixed effects models were used to analyze the effect of the alarms on surface feeding, swimming speed, breathing rate, directness and dive time. We observed a significant decrease in surface feeding and a significant increase in swimming speed during exposure to the whale pinger. Changes in dive time between the phases of a trial differed significantly between individuals indicating that responses may depend on individual or behavioural state. We did not find any significant reactions in response to the seal scarer. In addition to the experimental exposures, a trial of whale pingers on a capelin purse seine net was conducted. Results from this trial showed that whales entered the net from the bottom while the pingers were attached at the top, but the encircled whales were able to locate an opening free of pingers and escape without damaging the net. Our results suggest that whale pingers may be a useful entanglement mitigation tool in humpback whale feeding grounds given that a reduction in feeding around nets likely reduces the risk of whales swimming through them. Pingers may also minimize net damage if whales are encircled by aiding the whales in finding their way out. However, given the uncertain long-term consequences of the behavioural changes reported here, whale pingers are most advisable for short-term use in conjunction with other entanglement mitigation measures.
GLAMbox: A Python toolbox for investigating the association between gaze allocation and decision behaviour
Authors: Molter Felix , Thomas Armin W. , Heekeren Hauke R. , Mohr Peter N. C.
Published: August 2019

Recent empirical findings have indicated that gaze allocation plays a crucial role in simple decision behaviour. Many of these findings point towards an influence of gaze allocation onto the speed of evidence accumulation in an accumulation-to-bound decision process (resulting in generally higher choice probabilities for items that have been looked at longer). Further, researchers have shown that the strength of the association between gaze and choice behaviour is highly variable between individuals, encouraging future work to study this association on the individual level. However, only few decision models exist that easily allow studying the gaze-choice association on the individual level, due to the high cost of developing and implementing them. The model space is particularly scarce for choice sets with more than two choice alternatives. Here, we present GLAMbox, a Python-based toolbox that is built upon PyMC3 and allows the easy application of the gaze-weighted linear accumulator model (GLAM) to experimental choice data. The GLAM assumes gaze-dependent evidence accumulation in a linear stochastic race that extends to decision scenarios with many choice alternatives. GLAMbox enables Bayesian parameter estimation of the GLAM for individual, pooled or hierarchical models, provides an easy-to-use interface to predict choice behaviour and visualize choice data, and benefits from all of PyMC3’s Bayesian statistical modeling functionality. Further documentation, resources and the toolbox itself are available athttps://github.com/glamlab/glambox.
HypercubeME: two hundred million combinatorially complete datasets from a single experiment
Authors: Esteban Laura Avino , Lonishin Lyubov R. , Bobrovskiy Daniil , Leleytner Gregory , Bogatyreva Natalya S. , Kondrashov Fyodor A. , Ivankov Dmitry N.
Published: August 2019

Motivation

Epistasis, the context-dependence of the contribution of an amino acid substitution to fitness, is common in evolution. To detect epistasis, fitness must be measured for at least four genotypes: the reference genotype, two different single mutants and a double mutant with both of the single mutations. For higher-order epistasis of the order n, fitness has to be measured for all 2n genotypes of an n-dimensional hypercube in genotype space forming a “combinatorially complete dataset”. So far, only a handful of such datasets have been produced by manual curation. Concurrently, random mutagenesis experiments have produced measurements of fitness and other phenotypes in a high-throughput manner, potentially containing a number of combinatorially complete datasets.

Results

We present an effective recursive algorithm for finding all hypercube structures in random mutagenesis experimental data. To test the algorithm, we applied it to the data from a recent HIS3 protein dataset and found all 199,847,053 unique combinatorially complete genotype combinations of dimensionality ranging from two to twelve. The algorithm may be useful for researchers looking for higher-order epistasis in their high-throughput experimental data.

Availability

https://github.com/ivankovlab/HypercubeME.git.
Interactions between earliest Linearbandkeramik farmers and central European hunter gatherers at the dawn of European Neolithization
Authors: Nikitin Alexey G. , Stadler Peter , Kotova Nadezhda , Teschler-Nicola Maria , Price T. Douglas , Hoover Jessica , Kennett Douglas J. , Lazaridis Iosif , Rohland Nadin , Lipson Mark , Reich David
Published: August 2019

Archaeogenetic research over the last decade has demonstrated that European Neolithic farmers (ENFs) were descended primarily from Anatolian Neolithic farmers (ANFs). ENFs, including early Neolithic central European Linearbandkeramik (LBK) farming communities, also harbored ancestry from European Mesolithic hunter gatherers (WHGs) to varying extents, reflecting admixture between ENFs and WHGs. However, the timing and other details of this process are still imperfectly understood. In this report, we provide a bioarchaeological analysis of three individuals interred at the Brunn 2 site of the Brunn am Gebirge-Wolfholz archeological complex, one of the oldest LBK sites in central Europe. Two of the individuals had a mixture of WHG-related and ANF-related ancestry, one of them with approximately 50% of each, while the third individual had approximately all ANF-related ancestry. Stable carbon and nitrogen isotope ratios for all three individuals were within the range of variation reflecting diets of other Neolithic agrarian populations. Strontium isotope analysis revealed that the ~50% WHG-ANF individual was non-local to the Brunn 2 area. Overall, our data indicate interbreeding between incoming farmers, whose ancestors ultimately came from western Anatolia, and local HGs, starting within the first few generations of the arrival of the former in central Europe, as well as highlighting the integrative nature and composition of the early LBK communities.
The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility
Authors: Yanovsky Rebecca L. , Chen Haoyan , Leslie Stephen , Carrington Mary , Liao Wilson
Published: August 2019

Genetic variation within the major histocompatibility complex (MHC) class I is a well-known risk factor for psoriasis. While the mechanisms behind this variation are still being fully elucidated, human leukocyte antigen (HLA) presentation of auto-antigens as well as the interaction of HLA-B with killer cell immunoglobulin-like receptors (KIRs) have been shown to contribute to psoriasis susceptibility. Here we demonstrate that the interaction of HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR), a related group of immunomodulatory receptors primarily found on antigen presenting cells, also contributes to psoriasis susceptibility. We used previously characterized binding capacities of HLA-A, HLA-B, and HLA-C allotypes to two inhibitory LILRs, LILRB1 and LILRB2, to investigate the effect of LILRB1/2 binding in two large genome wide association study cohorts of psoriasis patients and controls (N = 10,069). We found that the strength of binding of LILRB2 to HLA-B was inversely associated with psoriasis risk (p = 2.34E-09, OR [95% CI], 0.41 [0.30−0.55]) independent of individual class I or II allelic effects. We thus propose that weak binding of inhibitory LILRB2 to HLA-B may play a role in patient susceptibility to psoriasis via increased activity of antigen presenting cells.
Cross-compatibility of five highbush blueberry varieties and ideal crossing combinations
Authors: Martin Keanu , Minnaar Corneile , Jager Marinus de , Anderson Bruce
Published: August 2019

Blueberry plants require large quantities of pollen deposited on stigmas to produce commercial-quality fruit. Like many agricultural crops, the interaction between pollen-source variety and pollen-recipient variety can be a major determinant of fruit quality in blueberries. However, little information exists to guide growers in optimising fruit set and quality. Using five commonly grown blueberry varieties, I determined whether crossing between varieties (inter-varietal) increased fruit mass and decreased developmental time relative to crossing within a variety (intra-varietal), and if so, what the best crossing combinations are. While intra-varietal pollination often produced fruit, for certain varieties the fruit set and fruit mass were highly reduced compared to inter-varietal pollination. Furthermore, intra-varietal pollination resulted in longer fruit developmental time in comparison to pollination between varieties. For the same pollen-recipient variety, inter-varietal crosses typically outperformed intra-varietal crosses in fruit mass and developmental time; however, the extent to which inter-varietal crosses outperformed intra-varietal crosses differed between pollen-donor varieties. This result suggests that combinations of varieties are not trivial as some inter-varietal combinations may outperform others. Furthermore, some varieties appear to be more susceptible to the negative effects of intra-varietal crosses than others and that less susceptible varieties may be better suited to conditions where pollinator movement is poor. While our study can guide growers in determining optimal co-planting schemes for the varieties tested, for example in South Africa where these varieties are frequently grown. It also serves as a blueprint for similar compatibility studies that can easily be performed prior to planting to determine the best inter-varietal combinations.
Accurate and Efficient Cell Lineage Tree Inference from Noisy Single Cell Data: the Maximum Likelihood Perfect Phylogeny Approach
Authors: Wu Yufeng
Published: August 2019

Cells in an organism share a common evolutionary history, called cell lineage tree. Cell lineage tree can be inferred from single cell genotypes at genomic variation sites. Cell lineage tree inference from noisy single cell data is a challenging computational problem. Most existing methods for cell lineage tree inference assume uniform uncertainty in genotypes. A key missing aspect is that real single cell data usually has non-uniform uncertainty in individual genotypes. Moreover, existing methods are often sampling-based and can be very slow for large data.

In this paper, we propose a new method called ScisTree, which infers cell lineage tree and calls genotypes from noisy single cell genotype data. Different from most existing approaches, ScisTree works with genotype probabilities of individual genotypes (which can be computed by existing single cell genotype callers). ScisTree assumes the infinite sites model. Given uncertain genotypes with individualized probabilities, ScisTree implements a fast heuristic for inferring cell lineage tree and calling the genotypes that allow the so-called perfect phylogeny and maximize the likelihood of the genotypes. Through simulation, we show that ScisTree performs well on the accuracy of inferred trees, and is much more efficient than existing methods. The efficiency of ScisTree enables new applications including imputation of the so-called doublets.

Availability

The program ScisTree is available for download at: https://github.com/yufengwudcs/ScisTree

Contact

yufeng.wu@uconn.edu
Simplified Methodology for a Modular and Genetically Expanded Protein Synthesis in Cell-Free Systems
Authors: Chemla Yonatan , Ozer Eden , Shaferman Michael , Zaad Ben , Dandela Rambabu , Alfonta Lital
Published: August 2019

Genetic code expansion, which enables the site-specific incorporation of unnatural amino acids into proteins, has emerged as a new and powerful tool for protein engineering. Currently, it is mainly utilized inside living cells for a myriad of applications. However, utilization of this technology in a cell-free, reconstituted platform has several advantages over living systems. The common limitations to the employment of these systems are the laborious and complex nature of its preparation and utilization. Herein, we describe a simplified method for the preparation of this system from Escherichia coli cells, which is specifically adapted for the expression of the components needed for cell-free genetic code expansion. In addition, we propose and demonstrate a modular approach to its utilization. By this approach, it is possible to prepare and store different extracts, harboring various translational components, and mix and match them as needed for more than four years retaining its high efficiency. We demonstrate this with the simultaneous incorporation of two different unnatural amino acids into a reporter protein. Finally, we demonstrate the advantage of cell-free systems over living cells for the incorporation of δ-thio-boc-lysine into ubiquitin by using the methanosarcina mazei wild-type pyrrolysyl tRNACUA and tRNA-synthetase pair, which can not be achieved in a living cell.
Distinct structure-function relationships across cortical regions and connectivity scales in the rat brain
Authors: Straathof Milou , Sinke Michel R.T. , Roelofs Theresia J.M. , Blezer Erwin L.A. , Sarabdjitsingh R. Angela , van der Toorn Annette , Schmitt Oliver , Otte Willem M. , Dijkhuizen Rick M.
Published: August 2019

An improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in many disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Our main goal was to identify to what extent structural and functional connectivity strengths are correlated, macro- and meso-scopically, across the cortex. Correlation analyses revealed a positive correspondence between functional connectivity and macro-scale diffusion-based structural connectivity, but no correspondence between functional connectivity and meso-scale neuronal tracer-based structural connectivity. Locally, strong functional connectivity was found in two well-known resting-state networks: the sensorimotor and default mode network. Strong functional connectivity within these networks coincided with strong short-range intrahemispheric structural connectivity, but with weak heterotopic interhemispheric and long-range intrahemispheric structural connectivity. Our study indicates the importance of combining measures of connectivity at distinct hierarchical levels to accurately determine connectivity across networks in the healthy and diseased brain. Distinct structure-function relationships across the brain can explain the organization of networks and may underlie variations in the impact of structural damage on functional networks and behavior.
ER stress-linked autophagy stabilizes apoptosis effector PERP and triggers its co-localization with SERCA2b at ER-plasma membrane junctions
Authors: McDonnell Samantha J. , Spiller David G. , White Michael R. H. , Prior Ian A. , Paraoan Luminita
Published: August 2019

Specific molecular interactions that underpin the switch between ER stress-triggered autophagy-mediated cellular repair and cellular death by apoptosis are not characterized. This study reports the unexpected interaction elicited by ER stress between the plasma membrane (PM)-localized apoptosis effector PERP and the ER Ca2+ pump SERCA2b. We show that the p53 effector PERP, which specifically induces apoptosis when expressed above a threshold level, has a heterogeneous distribution across the PM of un-stressed cells and is actively turned over by the lysosome. PERP is upregulated following sustained starvation-induced autophagy, which precedes the onset of apoptosis indicating that PERP protein levels are controlled by a lysosomal pathway that is sensitive to cellular physiological state. Furthermore, ER stress stabilizes PERP at the PM and induces its increasing co-localization with SERCA2b at ER-PM junctions. The findings highlight a novel crosstalk between pro-survival autophagy and pro-death apoptosis pathways and identify, for the first time, accumulation of an apoptosis effector to ER-PM junctions in response to ER stress.
Mg2+Impacts the Twister Ribozyme through Push-Pull Stabilization of Non-Sequential Phosphate Pairs
Authors: Kognole A. A. , MacKerell A. D.
Published: August 2019

RNA molecules perform a variety of biological functions for which the correct three-dimensional structure is essential, including as ribozymes where they catalyze chemical reactions. Metal ions, especially Mg2+, neutralize these negatively charged nucleic acids and specifically stabilize RNA tertiary structures as well as impact the folding landscape of RNAs as they assume their tertiary structures. Specific binding sites of Mg2+in folded conformations of RNA have been studied extensively, however, the full range of interactions of the ion with compact intermediates and unfolded states of RNA is challenging to investigate and the atomic details of the mechanism by which the ion facilitates tertiary structure formation is not fully known. Here, umbrella sampling combined with oscillating chemical potential Grand Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) simulations are used to capture the energetics and atomic-level details of Mg2+-RNA interactions that occur along an unfolding pathway of the Twister ribozyme. The free energy profiles reveal stabilization of partially unfolded states by Mg2+, as observed in unfolding experiments, with this stabilization being due to increased sampling of simultaneous interactions of Mg2+with two or more non-sequential phosphate groups. Notably, the present results indicate a push-pull mechanism where the Mg2+-RNA interactions actually lead to destabilization of specific non-sequential phosphate-phosphate interactions while other interactions are stabilized, a balance that facilitates the folding and stabilization of Twister including formation hydrogen bonds associated with the tertiary structure. The present study establishes a better understanding of how Mg2+ion-interactions contribute to RNA structural properties and stability.

Statement of Significance

RNAs are biologically and therapeutically of great emerging interest such that it is critical to understand how RNA molecules fold into complex structures. While experiments yield information on the stabilization of RNA by ions they are limited in the atomic-level insights they can provide. A combination of enhanced sampling methods is applied to explore the compact intermediate states of RNA and their interactions with Mg2+ions. Results reveal a picture of how Mg2+overall stabilizes short phosphate-phosphate interactions thereby facilitating the stabilization of RNA, though doing so by both the stabilization and destabilization of specific interactions. The applied method will be applicable to exploring the impact of divalent ions on the conformational heterogeneity of a range of macromolecules.
State-space approach to capital return in nonlinear growth processes
Authors: Kärenlampi Petri P.
Published: August 2019

Purpose

The purpose of this paper is to introduce a capital return rate function for growth processes, and apply it to financial sustainability considerations in growing multiannual plants.

Design/methodology/approach

A partition function of change rate of capitalization is introduced, as well as that of capitalization itself, and the expected value of capital return rate is produced as the ratio of the two functions.

Findings

Financial sustainability significantly differs from maximum-yield sustainability, and does not depend on any external interest rate.

Research limitations/implications

It is proposed that financial considerations should not be based on any arbitrary external interest. Neither should the shape of any yield function be neglected. Constancy of capital return rate in time is not assumed.

Practical implications

Two forestry examples show that the capital return rate is sensitive to rotation time, and in particular to the level of initial investment. The proposed procedure can be applied in the absence of periodic boundary conditions in time.

Originality/value

The methodology has not been applied in this field previously.
The influence of audit committee’s and company’s characteristic on intellectual capital disclosure
Authors: Naimah Zahroh , Mukti Nico Acintyo
Published: August 2019

Purpose

The purpose of this paper is to test the influences of audit committee’s and company’s characteristic on intellectual capital disclosure (ICD) among the LQ45-listed companies in Indonesia Stock Exchange (BEI) between 2013 and 2014.

Design/methodology/approach

The paper employed multiple linear regression and saturation sample as the analysis methods.

Findings

The findings showed that size of audit committee does not significantly influence ICD; meeting frequency of audit committee positively influences ICD; and company size does not influence ICD positively. On the other hand, profitability does not significantly influence ICD; leverage has negative and significant influence on ICD; and the type of industry does not significantly influence intellectual capital disclosure.

Originality/value

As there are few ICD studies, this research will surely add ICD antecedents to literature.
A comparative analysis of long-term performance of construction and non-construction IPOs in India
Authors: Kumar Singla Harish
Published: August 2019

Purpose

The purpose of this paper is to analyze the long-term performance of construction sector initial public offers (IPO) made in India during 2006–2015. The study aims to compare the performance of the construction sector IPOs with the non-construction sector IPOs and finds the determinants of long-term performance of construction sector IPO with a time horizon of three years. The study also attempts to find out, if the long-term IPO underpricing that has been discussed in the literature, really exists or it is a myth.

Design/methodology/approach

The study uses data of IPOs listed on National stock exchange during 2006–2015. In total, 281 IPOs are considered for the study, among which 44 are construction sector IPOs. IPOs anniversary performance of three successive years is calculated from the date of listing, and a random effect panel regression model with clustered robust estimates using the maximum likelihood method is performed to find out the determinants of IPO performance. The data are also tested for multicollinearity, stationarity and heteroscedasticity to ensure the robustness of results.

Findings

The results show that in the long-run construction sector IPOs outperform the non-construction sector IPOs, though the performance is below average when compared to market returns. The IPO underpricing is a myth, and IPO underperformance is a reality in India. The performance of construction sector IPOs is driven positively by market return, size of the firm and negatively by liquidity of the firm.

Originality/value

The paper is the first attempt to analyze the performance of construction sector IPOs, and compare it with non-construction sector IPOs. The study uses a random effect panel regression model with robust estimates using the maximum likelihood method to ensure the robustness of results. This is the first time the performance of IPOs is studied with a panel data approach.
Leadership, uncertainty and risk: how leaders influence teachers
Authors: Twyford Kaye , Le Fevre Deidre
Published: August 2019

Purpose

The purpose of this paper is to examine how the actions of leaders influence teachers’ perceptions of risk and sensemaking during professional learning (PL).

Design/methodology/approach

A qualitative case study primarily involving semi-structured interviews was utilized to collect teacher-perception data. In total, 21 teachers across three New Zealand schools were interviewed as they participated in the first year of a school-wide PL initiative. Data were analyzed using a risk perception lens focused on uncertainty.

Findings

Teachers’ perceptions of risk were influenced by leaders’ actions. Leaders built supportive relationships by knowing the teacher as a learner; showing empathy and respect; providing support; and engendering trust. Teachers reported that the quality of relationships combined with their own state of knowledge influenced their perceptions of risk and learning.

Practical implications

Leaders are reminded that learning is inherently uncertain and uncomfortable and that they have an important role to ensure an environment that is safe and supportive for teacher risk taking and change. A risk lens enables leaders and PL facilitators to consider their influence on teachers’ uncertainty and feelings of vulnerability and take action to reduce these where possible so that both teacher and student learning may be maximized.

Originality/value

This research advances the conceptualization of perceived risk in professional learning, emphasizing the importance of leadership in supporting teacher learning. It adds further detail to our understanding of trust, vulnerability, identity and risk in the development of professional capital and community and their connection to the professional and emotional lives of teachers.
Investors’ risk aversion integration and quantitative easing
Authors: Fassas Athanasios , Papadamou Stephanos , Philippas Dionisis
Published: August 2019

Purpose

The purpose of this paper is to examine the spillover effects in international financial markets related to investors’ risk aversion as proxied by the variance premium, and how these relationships were affected by the quantitative easing (QE) announcements by the Federal Reserve.

Design/methodology/approach

The empirical analysis employs a multivariate exponential generalized autoregressive conditionally heteroskedastic (VAR-EGARCH) specification, which includes the USA, the UK, Germany, France and Switzerland.

Findings

Two main findings are raised from the empirical analysis. First, the VAR-EGARCH model identifies statistically significant spillover effects identifying the USA as the leading source driving investors’ risk aversion. Second, unconventional monetary easing announcement by the Fed has had significant effects on investors’ risk perspectives.

Practical implications

Accounting for the dynamic volatility of variance premium inter-dependencies, the authors show that the correlations among variance premia increase during the QE announcements by the Federal Reserve, suggesting a herding behavior that may potentially lead to stock price bubbles and undermine financial stability.

Originality/value

This is an empirical attempt that investigates the unexplored effects of unconventional monetary policy decisions in relation with investors’ attitudes toward risk.