bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Inaccurate Response Function Calibration on Characteristics of the Fiber Orientation Distribution in Diffusion MRI
Authors: Guo Fenghua , Tax Chantal M.W. , Luca Alberto De , Viergever Max A. , Heemskerk Anneriet , Leemans Alexander 
Published: September 2019

AbstractDiffusion MRI of the brain enables to quantify white matter fiber orientations noninvasively. Several approaches have been proposed to estimate such characteristics from diffusion MRI data with spherical deconvolution being one of the most widely used methods. Constrained spherical deconvolution requires to define – or derive from the data – a response function, which is used to compute the fiber orientation distribution (FOD). This definition or derivation is not unequivocal and can thus result in different characteristics of the response function which are expected to affect the FOD computation and the subsequent fiber tracking. In this work, we explored the effects of inaccuracies in the shape and scaling factors of the response function on the FOD characteristics. With simulations, we show that underestimation of the shape factor in the response functions has a larger effect on the FOD peaks than overestimation of the shape factor, whereas the latter will cause more spurious peaks. Moreover, crossing fiber populations with a smaller separation angle were more sensitive to the response function inaccuracy than fiber populations with more orthogonal separation angles. Furthermore, the FOD characteristics show deviations as a result of modified shape and scaling factors of the response function. Results with the in vivo data demonstrate that the deviations of the FODs and spurious peaks can further deviate the termination of propagation in fiber tracking. This work highlights the importance of proper definition of the response function and how specific calibration factors can affect the FOD and fiber tractography results.
Vegetation and soil seedbank dynamics inParthenium hysterophorusL. invaded subtropical grassland in Nepal
Authors: Rokaya Maan Bahadur , Khatri-Chettri Jyoti , Ghimire Shiba Raj , Shrestha Bharat Babu 
Published: September 2019

AbstractParthenium hysterophorusis a noxious invasive weed and is ever expanding in its introduced range including Nepal. Understanding vegetation dynamics including soil seedbank inPartheniuminvaded communities and the growth pattern of the weed itself is essential for effective management ofParthenium. We monitored growth ofParthenium(height, density, cover and soil seedbank) and plant species composition of associated species for 5-year period from 2009 in a grassland invaded byPartheniumin south-central Nepal. We found thatPartheniumcover and height decreased from 2009 to 2010 and then slightly increased in 2013.Partheniumdensity decreased from 2009 to 2010 and then was variable until 2013. Year × grazing interactions had significant effect onPartheniumcover and density.Partheniumsoil seedbank was eight times higher near the soil surface than in deep soil. It increased from 2009 to 2012 but decreased in 2013. Seedbank was also affected by interactions of year × depth, depth × grazing, and year × depth × grazing. Altogether, 87 plant species were recorded inPartheniuminvaded sites and their species richness decreased until 2012 but slightly increased in 2013. The composition of associated plant species was affected by animal grazing intensity,Partheniumdensity, cover, and their interactions.Partheniuminvasion has been ever increasing in our study site and many palatable plant species are under potential threat. Thus, there is an urgent need to carry out awareness campaign, formulate proper management plans, and implement such plans properly to managePartheniumweed in Nepal.
Immediate early gene kakusei plays a role in the daily foraging and learning of honey bees
Authors: Singh Asem Surindro , Cappelletti Pamela , Feligioni Marco 
Published: September 2019

Abstractkakuseiis a non-coding RNA that is overexpressed in foraging bee brain. This study describes a fundamental role of the IEGkakuseiduring the daily foraging of honey bees.kakuseiwas found to be transiently upregulated within two hours during rewarded foraging. Interestingly, during unrewarded foraging the gene was also found to be up-regulated, but immediately lowered as food was not rewarded. Moreover, thekakuseioverexpression was diminished within a very short time when the time schedule of feeding was changed. This indicates the potential role ofkakuseion the motivation of learned reward foraging, reflecting associative learning memory. These results provide evidence for a dynamic role ofkakuseiduring foraging of bees, and eventually its possible involvement in learning and memory. Thus thekakuseigene could be used as key search tool in finding distinct molecular pathways that mediate diverse behavioral components of foraging.
Specialization for cell-free or cell-to-cell spread of BAC-cloned HCMV strains is determined by factors beyond the UL128-131 and RL13 loci
Authors: Schultz Eric P. , Lanchy Jean-Marc , Day Le Zhang , Yu Qin , Peterson Christopher , Preece Jessica , Ryckman Brent J. 
Published: September 2019

ABSTRACTIt is widely held that clinical isolates of human cytomegalovirus (HCMV) are highly cell-associated, and mutations affecting the UL128-131 and RL13 loci that arise in culture lead to the appearance of a cell-free spread phenotype. The BAC-clone Merlin (ME), expresses abundant UL128-131, is RL13-impaired and produces low infectivity virions in fibroblasts, whereas TB40/e (TB) and TR are low in UL128-131, RL13-intact and produce virions of much higher infectivity. Despite these differences, quantification of spread by flow cytometry revealed remarkably similar spread efficiencies in fibroblasts. In epithelial cells, ME spread more efficiently, consistent with robust UL128-131 expression. Strikingly, ME spread far better than TB or TR in the presence of neutralizing antibodies on both cell types, indicating that ME is not simply deficient at cell-free spread, but is particularly efficient at cell-to-cell spread, whereas TB and TR cell-to-cell spread is poor. Sonically disrupted ME-infected cells contained scant infectivity, suggesting that the efficient cell-to-cell spread mechanism of ME depends on features of the intact cells such as junctions or intracellular trafficking processes. Even when UL128-131 was transcriptional repressed, cell-to-cell spread of ME was still more efficient than TB or TR. Moreover, RL13 expression comparably reduced both cell-free and cell-to-cell spread of all three strains, suggesting that it acts at a stage of assembly and/or egress common to both routes of spread. Thus, HCMV strains can be highly specialized for either for cell-free or cell-to-cell spread and these phenotypes are determined by factors beyond the UL128-131 or RL13 loci.IMPORTANCEBoth cell-free and cell-to-cell spread are likely important for the natural biology of HCMV. In culture, strains clearly differ in their capacity for cell-free spread as a result of differences in the quantity and infectivity of extracellular released progeny. However, it has been unclear whether “cell-associated” phenotypes are simply the result of poor cell-free spread, or are indicative of particularly efficient cell-to-cell spread mechanisms. By measuring the kinetics of spread at early time points, we were able to show that HCMV strains can be highly specialized to either cell-free or cell-to-cell mechanisms, and this was not strictly linked the efficiency of cell-free spread. Our results provide a conceptual approach to evaluating intervention strategies for their ability to limit cell-free or cell-to-cell spread as independent processes.
Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: a case study in the Amazon Basin
Authors: Corder Rodrigo M. , Ferreira Marcelo U. , Gomes M. Gabriela M. 
Published: September 2019

AbstractThe overall malaria burden in the Americas has decreased dramatically over the past two decades, but residual transmission pockets persist across the Amazon Basin, where Plasmodium vivax is the predominant infecting species. Current elimination efforts require a better quantitative understanding of malaria transmission dynamics for planning, monitoring, and evaluating interventions at the community level. This can be achieved with mathematical models that properly account for risk heterogeneity in communities approaching elimination, where few individuals disproportionately contribute to overall malaria prevalence, morbidity, and onwards transmission. Here we analyse demographic information combined with routinely collected malaria morbidity data from the town of Mâncio Lima, the main urban transmission hotspot of Brazil. We estimate the proportion of high-risk subjects in the host population by fitting compartmental susceptible-infected-susceptible (SIS) transmission models simultaneously to age-stratified vivax malaria incidence densities and the frequency distribution of P. vivax malaria attacks experienced by each individual over 12 months. Simulations with the best-fitting SIS model indicate that 20% of the hosts contribute 86% of the overall vivax malaria burden. Despite the low overall force of infection typically found in the Amazon, about one order of magnitude lower than that in rural Africa, high-risk individuals gradually develop clinical immunity following repeated infections and eventually constitute a substantial infectious reservoir comprised of asymptomatic parasite carriers that is overlooked by routine surveillance but likely fuels onwards malaria transmission. High-risk individuals therefore represent a priority target for more intensive and effective interventions that may not be readily delivered to the entire community.
A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6
Authors: Vondrova L. , Adamus M. , Nociar M. , Kolesar P. , Oliver A.W. , Palecek J.J. 
Published: September 2019

ABSTRACTThe SMC (Structural Maintenance of Chromosomes) complexes are composed of SMC dimers, kleisin and kleisin-interacting subunits. Mutual interactions of these subunits constitute the basal architecture of the SMC complexes. Particularly, terminal domains of the kleisin subunit bridge the SMC head domains of the SMC molecules. Binding of ATP molecules to the heads and their hydrolysis alter the shape of long SMC molecules (from rod-like to open-ring shapes) and power them with motor activity. The kleisin-interacting (HAWK or KITE) subunits bind kleisin linker regions and regulate such dynamic activities.We developed new systems to follow the interactions between SMC5/6 subunits and stability of the SMC5/6 complexes. First, we show that the N-terminal domain of the Nse4 kleisin molecule binds to the SMC6 neck and bridges it to the SMC5 head. Second, binding of the Nse1 and Nse3 KITE proteins to the Nse4 linker part increases stability of the ATP-free SMC5/6 complex. In contrast, binding of ATP to the SMC5/6 complex containing KITE subunits significantly decreases its stability. Elongation of the Nse4 linker partially suppresses instability of the ATP-bound complex, suggesting that the binding of the KITE proteins to the Nse4 linker constrains its limited size. Our data suggest that the KITE proteins may shape the Nse4 linker to fit the ATP-free complex optimally and to facilitate opening of the complex upon ATP binding. This mechanism suggests an important role of the KITE subunits in the dynamics of the SMC5/6 complexes.AUTHOR SUMMARYThe SMC5/6 complex is member of the Structural maintenance of chromosomes (SMC) family, key organizers of both prokaryotic and eukaryotic genomes. Their architecture and dynamics (driven by ATP binding and hydrolysis) are essential for cellular processes, like chromatin segregation, condensation, replication and repair. In this paper, we described conserved mode of the Nse4 kleisin subunit binding to the SMC6 (similar to cohesin and condensin) and its bridging role. Furthermore, we showed different impact of the binding of the Nse1-Nse3 KITE subunits to the Nse4 kleisin bridge. Our study suggested that the KITE proteins modulate the stability of the SMC5/6 complex, depending on its binding and hydrolysis of ATP. Our findings uncover molecular mechanisms underlying dynamics of the SMC5/6 complexes.
Thickening of the cell wall increases the resistance ofS. cerevisiaeto commercial formulations of glyphosate
Authors: Ravishankar Apoorva , Pupo Amaury , Gallagher Jennifer E.G. 
Published: September 2019

AbstractThe use of glyphosate-based herbicides is widespread and despite its extensive use, its effects are yet to be deciphered completely. The additives in commercial formulations of glyphosate, though labeled as inert when used individually, have adverse effects when used in combination with other additives and the active ingredient. As a species,Saccharomyces cerevisiaehas a wide range of resistance to glyphosate-based herbicides. To investigate the underlying genetic differences between sensitive and resistant strains, global changes in gene expression were measured when yeast were exposed to a commercial formulation of glyphosate (CFG). Changes in gene expression involved in numerous pathways such as DNA replication, MAPK signaling, meiosis, and cell wall synthesis. Because so many diverse pathways were affected, these strains were then subjected to in-lab-evolutions (ILE) to select mutations that confer increased resistance. Common fragile sites were found to play a role in adaptation mechanisms used by cells to attain resistance with long-term exposure to CFG. The cell wall structure acts as a protective barrier in alleviating the stress caused by exposure to CFG. The thicker the cell wall, the more resistant the cell is against CFG. Hence, a detailed study of the changes occurring at the genome and transcriptome level is essential to better understand the possible effects of CFG on the cell as a whole.Author SummaryWe are exposed to various chemicals in the environment on a daily basis. Some of these chemicals are herbicides that come in direct contact with the food we consume. This makes the thorough investigation of these chemicals crucial. Some of the most commonly used herbicides around the world are glyphosate-based. Their mode of action effects a biosynthetic pathway that is absent in mammals and insects and so it is deemed safe for consumption. However, there are many additives to these herbicides that increase its effects. Thorough testing of these commercially available herbicides is essential to decipher all the potentially adverse effects that it could have on a cell.Saccharomyces cerevisiaehas a wide range of genetic diversity, making it is suitable to test different chemicals and identify any harmful effects. In this study, we exposed yeast cells to some glyphosate-based herbicides available in the market, to understand what effects it could have on a cell. We found that the additives in the herbicides have an effect on the cell wall and the mode of entry of glyphosate into the cell.
Developing a dengue forecast model using Long Short Term Memory neural networks method
Authors: Xu Jiucheng , Xu Keqiang , Li Zhichao , Tu Taotian , Xu Lei , Liu Qiyong 
Published: September 2019

AbstractBackgroundDengue Fever (DF) is a tropical mosquito-borne disease that threatens public health and causes enormous economic burdens worldwide. In China, DF expanded from coastal region to inner land, and the incidence sharply increased in the last few years. In this study, we conduct the analysis of dengue using the Long Short Term Memory (LSTM) recurrent neural networks. This is an artificial intelligence technology, to develop a precise dengue forecast model.Methodology/Principal FindingsThe model is developed from monthly dengue cases and local meteorological data of 2005–2018 among top 20 Chinese cities with a record of the highest dengue incidence. The first 13 year data were used to construct the LSTM and to predict the dengue outbreaks in 2018. The results are compared with the estimated dengue cases of other previously published models. Model performance and prediction accuracy were assessed using Root Mean Square Error (RMSE). With the LSTM method, the prediction measurements of average RMSE drop by 54.79% and 34.76% as compared with the Susceptible Infected Recovered (SIR) model and Zero Inflated Generalized Additive Model (ZIGAM). Our results showed that if only local data were used to develop forecast models, the LSTM neural networks would fail to capture the transmission characteristics of dengue virus in areas with fewer dengue cases. Contrarily, transfer learning (TL) can improve the accuracy of prediction of the LSTM neural network model in areas with fewer dengue incidences.Conclusion and significanceThe LSTM model is beneficial in predicting dengue incidence as compared with other previously published forecasting models. The findings provide a more precise forecast dengue model, which can help the local government and health-related departments respond early to dengue epidemics.Author summaryIn China, DF is a public health concern that poses a great economic burden on local governments. However, the incidence has sharply increased in recent years with growth in the sub-regions. With this issue, it will be challenging to develop an accurate and timely dengue forecast model. LSTM recurrent neural networks, deep learning methods and virus propagation rules by learning from observational data offer more advantages in predicting the prevalence of infectious disease dynamics than the traditional statistical model. The 2005–2017 data of the top 20 Chinese cities with the highest dengue incidence were used to construct the LSTM model, advantageous in predicting dengue in most cities. Moreover, the model helped to predict the dengue outbreaks in 2018 and used to compare the estimated dengue cases with the RMSE results of other previously published models. A thorough search of the literature shows that this is the first established dengue forecast model using the LSTM method, which is effective in predicting the trend of dengue dynamics.
A limited role for autophagy during arbovirus infection of mosquito cells
Authors: Brackney Doug E. , Correa Maria A. 
Published: September 2019

AbstractMacroautophagy is an evolutionarily conserved cellular process critical for maintaining cellular homeostasis. It can additionally function as an innate immune response to viral infection as has been demonstrated for a number of arthropod-borne (arbo-) viruses. Arboviruses are maintained in a transmission cycle between vertebrate hosts and invertebrate vectors yet the majority of studies assessing autophagy-arbovirus interactions have been limited to the mammalian host. Therefore we evaluated the role of autophagy during arbovirus infection of the invertebrate vector using the tractable Aag2Aedes aegyptimosquito cell culture system. Our data demonstrates that autophagy is significantly induced in mosquito cells upon infection with two flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), as well as an unrelated mosquito-borne virus, chikungunya virus (CHIKV;Togaviridae). While assessing the role of autophagy during arbovirus infection, we observed a somewhat paradoxical outcome. Both induction and suppression of autophagy via torin 1 and spautin-1, respectively, resulted in increased viral titers for all three viruses, yet suppression of autophagy-related genes had no effect. Interestingly, chemical modulators of autophagy had either no effect or opposite effects in another widely used mosquito cell line, C6/36Aedes albopictuscells. Together, our data reveals a limited role for autophagy during arbovirus infection of mosquito cells. Further, our findings suggest that commonly used chemical modulators of autophagy alter mosquito cells in such a way as to promote viral replication; however, it is unclear if this occurs directly through autophagic manipulation or other means.Author SummaryArthropod-borne (arbo) viruses, specifically those transmitted by Aedes aegypti mosquitoes, cause significant morbidity and mortality and pose a continued public health threat worldwide. Many of these viruses lack vaccines or therapeutics and current mosquito control strategies are underperforming. For these reasons, identifying vulnerabilities within the transmission cycle that can be targeted will be critical to the development of novel control interventions. Autophagy is a highly conserved cellular pathway and previous studies manipulating this pathway have shown promise in minimizing viral infections in mammalian hosts. In this study we examined arbovirus-autophagy interactions within vector mosquitoes. The goal was to elucidate the role of autophagy during infection of mosquitoes in hopes of identifying critical interactions that can be targeted by novel approaches to block infection of and transmission by vector mosquitoes.
The PAR2 signal peptide prevents premature receptor cleavage and activation
Authors: Liu Belinda , Lee Grace , Wu Jiejun , Deming Janise , Kuei Chester , Harrington Anthony , Wang Lien , Towne Jennifer , Lovenberg Timothy , Liu Changlu , Sun Siquan 
Published: September 2019

AbstractUnlike closely related GPCRs, protease-activated receptors (PAR1, PAR2, PAR3, and PAR4) have a predicted signal peptide at their N-terminus, which is encoded by a separate exon, suggesting that the signal peptides of PARs may serve an important and unique function, specific for PARs. In this report, we show that the PAR2 signal peptide, when fused to the N-terminus of IgG-Fc, effectively induced IgG-Fc secretion into culture medium, thus behaving like a classical signal peptide. The presence of PAR2 signal peptide has a strong effect on PAR2 cell surface expression, as deletion of the signal peptide (PAR2ΔSP) led to dramatic reduction of the cell surface expression and decreased responses to trypsin or the synthetic peptide ligand (SLIGKV). However, further deletion of the tethered ligand region (SLIGKV) at the N-terminus rescued the cell surface receptor expression and the response to the synthetic peptide ligand, suggesting that the signal peptide of PAR2 may be involved in preventing PAR2 from intracellular protease activation before reaching the cell surface. Supporting this hypothesis, an Arg36Ala mutation on PAR2ΔSP, which disabled the trypsin activation site, increased the receptor cell surface expression and the response to ligand stimulation. Similar effects were observed when PAR2ΔSP expressing cells were treated with protease inhibitors. Our findings indicated that these is a role of the PAR2 signal peptide in preventing the premature activation of PAR2 from intracellular protease cleavage before reaching the cells surface. The same mechanism may also apply to PAR1, PAR3, and PAR4.
A method of back-calculating the log odds ratio and standard error of the log odds ratio from the reported group-level risk of disease
Authors: Hu Dapeng , Wang Chong , O’Connor Annette M 
Published: September 2019

AbstractIn clinical trials and observational studies, the effect of an intervention or exposure can be reported as an absolute or relative comparative measure such as risk difference, odds ratio or risk ratio, or at the group level with the estimated risk of disease in each group. For meta-analysis of results with covariate adjustment, the log of the odds ratio (log odds ratio), with its standard error, is a commonly used measure of effect. However, extracting the adjusted log odds ratio from the reported estimates of disease risk in each group is not straightforward. Here, we propose a method to transform the adjusted probability of the event in each group to the log of the odds ratio and obtain the appropriate (approximate) standard error, which can then use used in a meta-analysis. We also use example data to compare our method with two other methods and show that our method is superior in calculating the standard error of the log odds ratio.