bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell analysis of the effects of developmental lead (Pb) exposure on the hippocampus
Authors: Bakulski Kelly M. , Dou John F. , Thompson Robert C. , Lee Christopher , Middleton Lauren Y. , Perera Bambarendage P. U. , Ferris Sean P. , Jones Tamara R. , Neier Kari , Zhou Xiang , Sartor Maureen A. , Hammoud Saher S. , Dolinoy Dana C. , Colacino Justin A. 
Published: December 2019

AbstractBackgroundLead (Pb) exposure is ubiquitous and has permanent developmental effects on childhood intelligence and behavior and adulthood risk of dementia. The hippocampus is a key brain region involved in learning and memory, and its cellular composition is highly heterogeneous. Pb acts on the hippocampus by altering gene expression, but the cell type-specific responses are unknown.ObjectiveExamine the effects of perinatal Pb treatment on adult hippocampus gene expression, at the level of individual cells, in mice.MethodsIn mice perinatally exposed to control water (n=4) or a human physiologically-relevant level (32 ppm in maternal drinking water) of Pb (n=4), two weeks prior to mating through weaning, we tested for gene expression and cellular differences in the hippocampus at 5-months of age. Analysis was performed using single cell RNA-sequencing of 5,258 cells from the hippocampus by 10x Genomics Chromium to 1) test for gene expression differences averaged across all cells by treatment; 2) compare cell cluster composition by treatment; and 3) test for gene expression and pathway differences within cell clusters by treatment.ResultsGene expression patterns revealed 12 cell clusters in the hippocampus, mapping to major expected cell types (e.g. microglia, astrocytes, neurons, oligodendrocytes). Perinatal Pb treatment was associated with 12.4% more oligodendrocytes (P=4.4×10−21) in adult mice. Across all cells, differential gene expression analysis by Pb treatment revealed cluster marker genes. Within cell clusters, differential gene expression with Pb treatment (q<0.05) was observed in endothelial, microglial, pericyte, and astrocyte cells. Pathways up-regulated with Pb treatment were protein folding in microglia (P=3.4×10−9) and stress response in oligodendrocytes (P=3.2×10−5).ConclusionBulk tissue analysis may be confounded by changes in cell type composition and may obscure effects within vulnerable cell types. This study serves as a biological reference for future single cell studies of toxicant or neuronal complications, to ultimately characterize the molecular basis by which Pb influences cognition and behavior.
An ALS-associated mutation in human FUS reduces neurotransmission fromC. elegansmotor neurons to muscles
Authors: Markert Sebastian M. , Skoruppa Michael , Yu Bin , Mulcahy Ben , Zhen Mei , Gao Shangbang , Sendtner Michael , Stigloher Christian 
Published: December 2019

AbstractAmytrophic lateral sclerosis (ALS) is a neurodegenerative disorder that has been associated with multiple genetic lesions, including mutations in the gene FUS (Fused in Sarcoma), an RNA/DNA-binding protein. Expression of the ALS-associated human FUS inC. elegansresults in mislocalization and aggregation of FUS outside the nucleus, and leads to impaired neuromuscular behaviors. However, the mechanisms by which mutant FUS disrupts neuronal health and function remain partially understood. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. Expression of ALS-associated FUS impairs synaptic vesicle docking at neuromuscular junctions, and leads to the emergence of a population of large and electron-dense filament-filled endosomes. Electrophysiological recording of neuromuscular transmission revealed reduced transmission from motor neurons to muscles. Together, these results suggest a potential direct or indirect role of human FUS in the organization of synaptic vesicles, and reduced transmission from motor neurons to muscles.Summary statementAn ALS-associated mutation in a trafficking protein disrupts the organization of theC. elegansneuromuscular junction.
Advancing motion denoising of multiband resting-state functional connectivity fMRI data
Authors: Williams John C. , Tubiolo Philip N. , Luceno Jacob R. , Van Snellenberg Jared X. 
Published: December 2019

AbstractSimultaneous multi-slice (multiband) accelerated functional magnetic resonance imaging (fMRI) provides dramatically improved temporal and spatial resolution for resting-state functional connectivity (RSFC) studies of the human brain in health and disease. However, multiband acceleration also poses unique challenges for denoising of subject motion induced data artifacts, the presence of which is a major confound in RSFC research that substantively diminishes reliability and reproducibility. We comprehensively evaluated existing and novel approaches to volume censoring-based motion denoising in the Human Connectome Project (HCP) dataset. We show that assumptions underlying common metrics for evaluating motion denoising pipelines, especially those based on quality control-functional connectivity (QC-FC) correlations and differences between high- and low-motion participants, are problematic, and appear to be inappropriate in their current widespread use as indicators of comparative pipeline performance and as targets for investigators to use when tuning pipelines for their own datasets. We further develop two new quantitative metrics that are instead agnostic to QC-FC correlations and other measures that rely upon the null assumption that no true relationships exist between trait measures of subject motion and functional connectivity, and demonstrate their use as benchmarks for comparing volume censoring methods. Finally, we develop and validate quantitative methods for determining dataset-specific optimal volume censoring parameters prior to the final analysis of a dataset, and provide straightforward recommendations and code for all investigators to apply this optimized approach to their own RSFC datasets.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
Authors: Bowles KR , Pugh DA , Liu Y , Renton AE , Bandres-Ciga S , Gan-Or Z , Heutink P , Siitonen A , Bertelsen S , Cherry JD , Karch CM , Frucht SJ , Kopell BH , Peter I , Park YJ ,   International Parkinson’s Disease Genomics Consortium (IPDGC), Charney A , Raj T , Crary JF , Goate AM 
Published: December 2019

ABSTRACTParkinson’s disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified. To better understand the genetic contribution of this region to PD, we fine-mapped the 17q21.31 locus in order to identify novel mechanisms conferring risk for the disease. We identified three novel H1 sub-haplotype blocks across the 17q21.31 locus associated with PD risk. Protective sub-haplotypes were associated with increased LRRC37A/2 copy number and expression in human brain tissue. We found that LRRC37A/2 is a membrane-associated protein that plays a role in cellular migration, chemotaxis and astroglial inflammation. In human substantia nigra, LRRC37A/2 was primarily expressed in astrocytes, interacted directly with soluble α-synuclein, and co-localized with Lewy bodies in PD brain tissue. These data indicate that a novel candidate gene, LRRC37A/2, contributes to the association between the 17q21.31 locus and PD via its interaction with α-synuclein and its effects on astrocytic function and inflammatory response. These data are the first to associate the genetic association at the 17q21.31 locus with PD pathology, and highlight the importance of variation at the 17q21.31 locus in the regulation of multiple genes other than MAPT and KANSL1, as well as its relevance to non-neuronal cell types.
Experimental Evaluation of Methods for Real-Time EEG Phase-Specific Transcranial Magnetic Stimulation
Authors: Shirinpour Sina , Alekseichuk Ivan , Mantell Kathleen , Opitz Alexander 
Published: December 2019

ABSTRACTBrain oscillations reflect system-level neural dynamics and capture the current brain state. These brain rhythms can be measured noninvasively in humans with electroencephalography (EEG). Up and down states of brain oscillations capture local changes in neuronal excitability. This makes them a promising target for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS). Real-time EEG-TMS systems record ongoing brain signals, process the data, and deliver TMS stimuli at a specific brain state. Despite their promise to increase the temporal specificity of stimulation, best practices and technical solutions are still under development. Here, we implement and compare state-of-the-art methods (Fourier based, Autoregressive Prediction) for real-time EEG-TMS and evaluate their performance both in silico and experimentally. We further propose a new robust algorithm for delivering real-time EEG phase-specific stimulation based on short prerecorded EEG training data (Educated Temporal Prediction). We found that Educated Temporal Prediction performs at the same level or better than Fourier-based or Autoregressive methods both in silico and in vivo, while being computationally more efficient. Further, we document a dependency of EEG signal-to-noise ratio (SNR) on algorithm accuracy across all algorithms. In conclusion, our results can give important insights for real-time TMS-EEG technical development as well as experimental design.
Longitudinal cell division is associated with single mutations in the FtsZ-recruiting SsgB inStreptomyces
Authors: Xiao Xiansha , Willemse Joost , Voskamp Patrick , Li Xinmeng , Lamers Meindert , Abrahams Jan Pieter , Pannu Navraj , van Wezel Gilles P. 
Published: December 2019

ABSTRACTIn most bacteria, cell division begins with the polymerization of the GTPase FtsZ at the mid-cell, which recruits the division machinery to initiate cell constriction. In the filamentous bacteriumStreptomyces, cell division is positively controlled by SsgB, which recruits FtsZ to the future septum sites and promotes Z-ring formation. Here we show via site-saturated mutagenesis that various amino acid substitutions in the highly conserved SsgB protein result in the production of ectopically placed septa, that sever spores diagonally or along the long axis, perpendicular to the division plane. Ectopic septa were especially prominent when cells expressed SsgB variants with substitutions in residue E120. Biochemical analysis of SsgB variant E120G revealed that its interaction with - and polymerization of - FtsZ had been maintained. The crystal structure ofS. coelicolorSsgB was resolved and the position of residue E120 suggests its requirement for maintaining the proper angle of helix α3, thus providing a likely explanation for the aberrant septa formed in SsgB E120 substitution mutants. Taken together, our work presents the first example of longitudinal division in a free living bacterium, which is explained entirely by changes in the FtsZ-recruiting protein SsgB.
Live analysis and reconstruction of single-particle cryo-electron microscopy data with CryoFLARE
Authors: Schenk Andreas D. , Cavadini Simone , Thomä Nicolas H. , Genoud Christel 
Published: December 2019

AbstractEfficient, reproducible and accountable single-particle cryo-electron microscopy structure determination is tedious and often impeded by lack of a standardized procedure for data analysis and processing. To address this issue, we have developed the FMI Live Analysis and Reconstruction Engine (CryoFLARE). CryoFLARE is a modular open-source platform offering easy integration of new processing algorithms developed by the cryo-EM community. It provides a user-friendly interface that allows fast setup of standardized workflows, serving the need of pharmaceutical industry and academia alike who need to optimize throughput of their microscope. To consistently document how data is processed, CryoFLARE contains an integrated reporting facility to create reports.Live analysis and processing parallel to data acquisition are used to monitor and optimize data quality. Problems at the level of the sample preparation (heterogeneity, ice thickness, sparse particles, areas selected for acquisition, etc.) or misalignments of the microscope optics can quickly be detected and rectified before data collection is continued. Interfacing with automated data collection software for retrieval of acquisition metadata reduces user input needed for analysis, and with it minimizes potential sources of errors and workflow inconsistencies. Local and remote export support in Relion-compatible job and data format allows seamless integration into the refinement process. The support for non-linear workflows and fine-grained scheduling for mixed workflows with separate CPU and GPU based calculation steps ensures optimal use of processing hardware. CryoFLARE’s flexibility allows it to be used for all types of image acquisitions, ranging from sample screening to high-resolution data collection, and offers a new alternative for setting up image processing workflows. It can be used without modifications of the hardware/software delivered by the microscope supplier. As it is running on a server in parallel to the hardware used for acquisition, it can easily be set up for remote display connections and fast control of the acquisition status.
Experimental evaluation of a hybrid electric propulsion system for small UAVs
Authors: Machado Leonardo , Matlock Jay , Suleman Afzal 
Published: December 2019

Purpose
This paper aims to experimentally evaluate the performance of a parallel hybrid propulsion system for use in small unmanned aerial vehicles (UAVs).

Design/methodology/approach
The objective is to combine all the individual components of the hybrid electric propulsion system (HEPS) into a modular test bench to characterize the performance of a parallel hybrid propulsion system, and to evaluate a rule-based controller based on the ideal operating line concept for the control of the power plant. Electric motor (EM) designed to supplement the power of the internal combustion engine (ICE) to reduce the overall fuel consumption, with the supervisory controller optimizing ICE torque.

Findings
The EM was able to supplement the power of the ICE to reduce fuel consumption, and proved the capability of acting as a generator to recharge the batteries drawing from ICE power. Furthermore, the controller showed that it is possible to reduce the fuel consumption with a HEPS when compared to its gasoline counterpart by running simulated representative UAV missions. The findings also highlighted the challenges to build and integrate the HEPS in small UAVs.

Originality/value
The modularity of the test bench allows each component to be changed to assess its impact on the performance of the system. This allows for further exploration and improvements of the HEPS in a controlled environment.
(Dis)aggregated earnings forecasts and acquisition financing
Authors: Ordyna Paul 
Published: December 2019

Purpose
The purpose of this paper is to examine how a firm’s mergers and acquisitions (M&A) goals influence its voluntary disclosure policy. Specifically, this paper examines how a firm’s M&A financing intentions influence the degree of aggregation in management guidance prior to and after the M&A transaction.

Design/methodology/approach
Using a logistic model, this study tests the relation between M&A financing and the decision to issue disaggregate earnings guidance for 3,929 acquiring firms from 2007 to 2011.

Findings
The logistic regression results show that firms are more likely to provide disaggregate earnings guidance when using mostly stock to finance M&A and that the incentives to disaggregate guidance vary throughout the M&A transactional window. Alternatively, because the value of cash is independent of the true value of the acquirer, the results show that firms offering mostly cash to finance M&A are less likely to issue disaggregate earnings forecasts. Additional analysis reveals that the decision to issue disaggregate earnings guidance also influences post-merger outcomes such as CEO turnover.

Research limitations/implications
The choice to disaggregate earnings guidance and the choice to use stock as a means to finance an acquisition is made by management, thus are endogenous which could introduce bias.

Originality/value
This study provides insights into management’s incentives and attitudes toward the use of management forecasts to effect a potential merger and acquisition. Given the flexibility management has in issuing voluntary forecasts, management can tailor a financial message toward investors and potential targets in attempt to facilitate a merger and acquisition and to further the firm’s goals.
Reasons for food losses during home preparation
Authors: Nonomura Maki 
Published: December 2019

Purpose
The purpose of this paper is to explore reasons for household preparation losses.

Design/methodology/approach
Observations of preparation behaviors and semi-structured interviews of nine people were conducted in their kitchens. The data were analyzed through a qualitative data analysis method.

Findings
Three types of preparation losses were identified, i.e. possibly avoidable food waste, excessive removals and unintentional losses. Possibly avoidable food waste and excessive removals were generated owing to people’s perception that is in the gray area between edible and inedible, their preferences, lower quality of food, convenience in preparation, lack of preparation skill and knowledge, and lack of concern about preparation losses. Unintentional losses were tiny pieces of food that were left on cooking tools.

Research limitations/implications
As this study’s participants were nine women living in Japan, further research is needed in order to achieve saturation.

Originality/value
Few studies have discussed reasons for preparation losses, and extant studies were based on a diary method and questionnaires. This present study uncovers several new reasons for preparation losses based on interviews and observations of consumer preparation behaviors. These new details would be helpful for campaigns or programs that aim to reduce food losses.
A breakthrough in business management (Roman private share company as radical novelty)
Authors: Petrosyan Armen E. 
Published: December 2019

Purpose
This paper aims to retrace the genesis of private share company in Ancient Rome as one of the greatest innovation in the history of management.

Design/methodology/approach
Relying on a thorough and systematic analysis of the available historical material, and modern research, the author reconstructs the first known form of private share company and the way it came into being under late Republic and early Empire.

Findings
The scope of commercial partnerships and bounds preventing them from concentration of capitals are shown. The popular myth of private corporations allegedly existing in Ancient Rome is debunked. The author reveals how existing business elements (union of co-owners, the module “slave – peculium – free administration” from individual enterprise, and the principle of inseparability of joint ownership) had been combined to form private share company. Are demonstrated its chief differences from corporation, and the untenability of attempts to deny the real existence of private share companies in Ancient Rome. By way of summing up, the pattern of innovations is brought into relief.

Research limitations/implications
The material opens new vistas for historians and allows them to draw an exacter and more comprehensive picture of Roman private entrepreneurship. Experts in management get an opportunity to retrace the background of modern forms of business organizing. A broader circle of researchers may see what the real path of radical novelties – from the need for them to their implementation – is. And altogether, the author’s conclusions provide scholars with a key to understanding breakthrough phenomena of history.

Practical implications
The results obtained may be used in many courses related to the history of economics, business, management, innovations, etc. Besides, they allow practitioners to discern plainly the origins of new business forms and learn how to make for them or facilitate their growth.

Social implications
The author's conception of viable novelties sheds light on the processes of social development and modernization. It may serve as an effective instrument in planning reforms and managing them.

Originality/value
The framework of Roman private share company and many allied issues are investigated for the first time. This type of enterprise is presented as a response to the functional request from private entrepreneurs. That is why the new organizational form, despite its radical nature, proved to be quite efficient, and caught on in business. The author infers from his findings a generalized pattern of innovations able to get integrated into reality.
An analysis of current tax revolt factors in South Africa
Authors: Du Preez Hanneke , Stoman Jacqueline 
Published: December 2019

PurposeThe purpose of this study is to determine whether the factors once identified through literature and compared to the current situation in South Africa could predict the possibility of a tax revolt in South Africa. South Africans are experiencing frequent increases in taxes on already overburdened taxpayers, corruption, a lack of service delivery by the government and high unemployment rates. South Africa has seen an increased amount of protests relating to taxes, corruption and a lack of basic services.Design/methodology/approachIn total, 12,000 Twitter feeds were collected from 14 February 2017 to 1 March 2017, the period before, during and after the South African National Budget Speech on 22 February 2017. The feeds were analysed using a thematic analysis. The emerging themes were identified as factors present in South Africa that may predict a possible tax revolt.FindingsThe factors found to be present in South Africa are: F1-failure of government to address the imminent collapse, F2-significant number of people with substantial debt, F3-onerous tax systems, including many different types of taxes, F4-high number of unemployed people, F5-education frustration, F6-increase in tax rates on citizens already overburdened by current taxes, F7-poor quality of governors, and performance of the country’s leaders and administration, including fraud and F8-wastefulness.Originality/valueThe value of the study is, first to contribute to the existing academic literature examining the factors that are likely to indicate a tax revolts. Second, the study uses an innovative data source, namely, tweets, to examine the climate for a possible tax revolt in South Africa.