bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA variation of Leber’s Hereditary Optic Neuropathy (LHON) in Western Siberia
Authors: Starikovskaya E.B. , Shalaurova S.A. , Dryomov S.V. , Nazhmidenova A.M. , Volodko N.V. , Bychkov I.Y. , Mazunin I.O. , Sukernik R.I. 
Published: August 2019

AbstractLeber’s hereditary optic neuropathy (LHON) is a form of disorder caused by pathogenic mutations in a mitochondrial DNA. LHON is maternally inherited disease, which manifests mainly in young adults, affecting predominantly males. Clinically LHON has a manifestation as painless central vision loss, resulting in early onset of disability. Epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients in the Western Siberia population. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53,10% (17/32), m.3460G>A – 21,90% (7/32), m.14484T>C – 18,75% (6/32), and rare m.10663T>C and m.3635G>A represent 6,25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.9444C>T, m.6261G>A, m.9921G>A, m.8551T>C, m.8412T>C, m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.
Comprehensive longitudinal study of epigenetic mutations in aging
Authors: Wang Yunzhang , Karlsson Robert , Jylhävä Juulia , Hedman Åsa K. , Almqvist Catarina , Karlsson Ida K. , Pedersen Nancy L. , Almgren Malin , Hägg Sara 
Published: August 2019

AbstractBackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.ResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.ConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.
Expression atlas of Selaginella moellendorffii provides insights into the evolution of vasculature, secondary metabolism and roots
Authors: Ferrari Camilla , Shivhare Devendra , Hansen Bjoern Oest , Winter Nikola , Pasha Asher , Esteban Eddi , Provart Nicholas J. , Kragler Friedrich , Fernie Alisdair , Tohge Takayuki , Mutwil Marek 
Published: August 2019

SummaryThe lycophyte Selaginella moellendorffii represents early vascular plants and is studied to understand the evolution of higher plant traits such as the vasculature, leaves, stems, roots, and secondary metabolism. However, little is known about the gene expression and transcriptional coordination of Selaginella genes, which precludes us from understanding the evolution of transcriptional programs behind these traits.We here present a gene expression atlas comprising all major organs, tissue types, and the diurnal gene expression profiles for S. moellendorffii. The atlas is part of the CoNekT-Plants database (conekt.plant.tools), which enables comparative transcriptomic analyses across two algae and seven land plants.We show that the transcriptional gene module responsible for the biosynthesis of lignocellulose evolved in the ancestor of vascular plants, and pinpoint the duplication and subfunctionalization events that generated multiple gene modules involved in the biosynthesis of various cell wall types. We further demonstrate how secondary metabolism is transcriptionally coordinated and integrated with other cellular pathways. Finally, we identify root-specific genes in vascular plants and show that the evolution of roots did not coincide with an increased appearance of gene families, suggesting that the existing genetic material was sufficient to generate new organs.Our updated database at conekt.plant.tools provides a unique resource to study the evolution of genes, gene families, transcriptomes, and functional gene modules in the Archaeplastida kingdom.
Performance evaluation of a new custom, multi-component DNA isolation method optimized for use in shotgun metagenomic sequencing-based aerosol microbiome research
Authors: Bøifot Kari Oline , Gohli Jostein , Moen Line Victoria , Dybwad Marius 
Published: August 2019

ABSTRACTBackgroundAerosol microbiome research advances our understanding of bioaerosols, including how airborne microorganisms affect our health and surrounding environment. Traditional microbiological/molecular methods are commonly used to study bioaerosols, but do not allow for generic, unbiased microbiome profiling. Recent studies have adopted shotgun metagenomic sequencing (SMS) to address this issue. However, SMS requires relatively large DNA inputs, which are challenging when studying low biomass air environments, and puts high requirements on air sampling, sample processing and DNA isolation protocols. Previous SMS studies have consequently adopted various mitigation strategies, including long-duration sampling, sample pooling, and whole genome amplification, each associated with some inherent drawbacks/limitations.ResultsHere, we demonstrate a new custom, multi-component DNA isolation method optimized for SMS-based aerosol microbiome research. The method achieves improved DNA yields from filter-collected air samples by isolating DNA from the entire filter extract, and ensures unbiased microbiome representation by combining chemical, enzymatic and mechanical lysis. Benchmarking against two state-of-the-art DNA isolation methods was performed with a mock microbial community and real-world subway air samples. All methods demonstrated similar performance regarding DNA yield and community representation with the mock community. However, with subway air samples, the new method obtained drastically improved DNA yields, while SMS revealed that the new method reported higher diversity and gave better taxonomic coverage. The new method involves intermediate filter extract separation into a pellet and supernatant fraction. Using subway air samples, we demonstrate that supernatant inclusion results in improved DNA yields. Furthermore, SMS of pellet and supernatant fractions revealed overall similar taxonomic composition but also identified differences that could bias the microbiome profile, emphasizing the importance of processing the entire filter extract.ConclusionsBy demonstrating and benchmarking a new DNA isolation method optimized for SMS-based aerosol microbiome research with both a mock microbial community and real-world air samples, this study contributes to improved selection, harmonization, and standardization of DNA isolation methods. Our findings highlight the importance of ensuring end-to-end sample integrity and using methods with well-defined performance characteristics. Taken together, the demonstrated performance characteristics suggest the new method could be used to improve the quality of SMS-based aerosol microbiome research in low biomass air environments.
Single-cell molecular and cellular architecture of the mouse neurohypophysis
Authors: Chen Qiyu , Leshkowitz Dena , Blechman Janna , Levkowitz Gil 
Published: August 2019

AbstractThe neurohypophysis (NH), located at the posterior lobe of the pituitary, is a major neuroendocrine tissue, which mediates osmotic balance, blood pressure, reproduction, and lactation by means of releasing the neurohormones oxytocin and arginine-vasopressin from the brain into the peripheral blood circulation. The major cellular components of the NH are hypothalamic axonal termini, fenestrated endothelia and pituicytes, the resident astroglia. However, despite the physiological importance of the NH, the exact molecular signature defining neurohypophyseal cell types and in particular the pituicytes, remains unclear. Using single cell RNA sequencing, we captured seven distinct cell types in the NH and intermediate lobe (IL) of adult male mouse. We revealed novel pituicyte markers showing higher specificity than previously reported. Single moleculein situhybridization revealed spatial organization of the major cell types implying intercellular communications. We present a comprehensive molecular and cellular characterization of neurohypophyseal cell-types serving as a valuable resource for further functional research.Significance StatementThe neurohypophysis (NH) is a major neuroendocrine interface, which allows the brain to regulate the function of peripheral organs in response to specific physiological demands. Despite its importance, a comprehensive molecular description of cell identities in the NH is still lacking. Utilizing single cell RNA sequencing technology, we identified the transcriptomes of five major neurohypophyseal cell types in the adult male mice and mapped the spatial distribution of selected cell typesin situ. We revealed an unexpected cellular heterogeneity of the neurohypophysis and provide novel molecular markers for neurohypophyseal cell types with higher specificity than previously reported.
The use of ATR-FTIR spectroscopy to characterise crude heparin samples by composition and structural features
Authors: Devlin Anthony , Mauri Lucio , Guerrini Marco , Yates Edwin A. , Skidmore Mark A. 
Published: August 2019

AbstractProduction of the major anticoagulant drug, heparin, is a complex process that begins with the collection of crude material from a dispersed network of suppliers with poor traceability, an issue that was made apparent in 2007-2008, when batches of heparin were contaminated deliberately in the supply chain, resulting in over 100 deaths in the US alone. Several analytical techniques are used currently for the characterisation of pharmaceutical grade heparin, but few have been applied to its crude counterpart. One exception is NMR spectroscopy which was used to study crude heparin (2017), however, owing to the high set-up and running costs, as well as the need for skilled technical operators, the use of NMR at crude heparin production plants is unviable. An alternative, practical, spectroscopic method is attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) that is user-friendly, economical and, importantly, requires little specialised training or sample preparation. Using a top-down chemometric approach employing principal component analysis, ATR-FTIR spectroscopy was able to distinguish crude heparins based on their similarity to pharmaceutical heparin, as well as on their compositional and structural features, which included levels of sulphation, the extent of related conformational changes, as well as the quantities of chondroitin and dermatan sulphate present. This approach lends itself to automation and will enable users and regulators to undertake quality control of crude heparin during manufacture. The method requires only economical, portable equipment and little specialised training, bringing the high-quality analysis of crude heparin within reach of both manufacturers and regulators for the first time.
Modeling the relationship between estimated foliar fungicide use and soybean yield losses due to foliar fungal diseases in the United States
Authors: Bandara Ananda Y. , Weerasooriya Dilooshi K. , Conley Shawn P. , Bradley Carl A. , Allen Tom W. , Esker Paul D. 
Published: August 2019

ABSTRACTFungicide use in the United States to manage soybean diseases has increased in recent years. The ability of fungicides to reduce disease-associated yield losses varies greatly depending on multiple factors. Nonetheless, historical data are useful to understand the broad sense and long-term trends related to fungicide use practices. In the current study, the relationship between estimated soybean yield losses due to selected foliar diseases and foliar fungicide use was investigated using annual data from 28 soybean growing states over the period of 2005 to 2015. At a national scale, a significant quadratic relationship was observed between total estimated yield losses and total fungicide use (R2 = 0.123, P < 0.0001) where yield losses initially increased, reached a plateau, and subsequently decreased with increasing fungicide use. The positive phase of the quadratic curve could be associated with insufficient amount of fungicides being used to manage targeted diseases, application of more-than-recommended prophylactic fungicides under no/low disease pressure, application of curative fungicides after economic injury level, and reduced fungicide efficacy due to a variety of factors such as unfavorable environmental conditions and resistance of targeted pathogen populations to the specific active ingredient applied. Interestingly, a significant quadratic relationship was also observed between total soybean production and total foliar fungicide use (R2= 0.36, P < 0.0001). The positive phase of the quadratic curve may suggest that factors like plant physiological changes, including increased chlorophyll content, photosynthetic rates, water use efficiency, and delayed senescence that have been widely reported to occur after application of certain foliar fungicides could have potentially contributed to enhanced yield. Therefore, the current study provides evidence of the potential usefulness of foliar fungicide applications to mitigate soybean yield losses associated with foliar diseases and their potential to positively impact soybean production/yield at national and regional scales although discrepancies to the general trends observed at national and regional scales do prevail at the local (state) level.
The impact of biological invasion and genomic local adaptation on the geographical distribution of Aedes aegypti in Panama
Authors: Bennett Kelly L. , McMillan W. Owen , Loaiza. Jose R. 
Published: August 2019

AbstractLocal adaptation is an important consideration when predicting arthropod-borne disease risk because it can impact on vector population fitness and persistence. However, the extent that vector populations are adapted to local environmental conditions and whether this can impact on species distributions generally remains unknown. Here we find that the geographic distribution of Ae. aegypti across Panama is rapidly changing as a consequence of the recent invasion by its ecological competitor, Aedes albopictus. Although Ae. albopictus has displaced Ae. aegypti in some areas, species coexist across many areas, raising the question: What biological and environmental factors permit population persistence?. Despite low population structure and high gene flow in Ae. aegypti across Panama, excepting the province of Bocas del Toro, we identify 128 candidate SNPs, clustered within 17 genes, which show a strong genetic signal of local adaptation. This putatively adaptive variation occurs across relatively fine geographic scales with the composition and frequency of candidate adaptive loci differing between populations in wet tropical environments along the Caribbean coast and the dry tropical conditions typical of the Pacific coast of Panama. Temperature and vegetation were important predictors of adaptive genomic variation in Ae. aegypti with potential areas of local adaptation occurring within the Caribbean region of Bocas del Toro, the Pacific coastal areas of Herrera and Panama City and the eastern Azuero Peninsula. Interestingly, several of these locations coincide with areas where Ae. aegypti and Ae. albopictus co-exist, suggesting that Ae. aegypti could have an adaptive edge under local environmental conditions that impacts on inter-specific competition with Ae. albopictus. Our results guide future experimental work by suggesting that locally adapted Ae. aegypti are able to persist on invasion by Ae. albopictus and, as a consequence, may fundamentally alter future arborviral disease risk and efforts to control mosquito populations.Author SummaryLocal environmental adaptation of mosquito vectors can alter the landscape of arthropod-borne disease by impacting on life history traits that increase their relative fitness thus promoting population persistence. We have identified a number of genomic loci in Ae. aegypti from Panama that exhibit a signal of natural selection associated with variation in the environment. Loci with a signal of local adaptation are predominately partitioned between wet and dry tropical environments with variation largely impacted by temperature and vegetation indices. Local adaptation in tandem with changes in the geographic distribution of Ae. aegypti due to the recent invasion of its ecological competitor, Ae. albopictus, has the potential to alter the landscape of arborviral disease.
Comparison of solitary and collective foraging strategies ofCaenorhabditis elegansin patchy food distributions
Authors: Ding Siyu Serena , Muhle Leah S. , Brown André E. X. , Schumacher Linus J. , Endres Robert G. 
Published: August 2019

AbstractCollective foraging has been shown to benefit organisms in environments where food is patchily distributed, but whether this is true in the case where organisms do not rely on long-range communications to coordinate their collective behaviour has been understudied. To address this question, we use the tractable laboratory model organismCaenorhabditis elegans, where a social strain (npr-1mutant) and a solitary strain (N2) are available for direct comparison of foraging strategies. We first developed an on-lattice minimal model for comparing collective and solitary foraging strategies, finding that social agents benefit from feeding faster and more efficiently simply due to group formation. Our laboratory foraging experiments withnpr-1and N2 worm populations, however, show an advantage for solitary N2 in all food distribution environments that we tested. We incorporated additional strain-specific behavioural parameters ofnpr-1and N2 worms into our model and computationally identified N2’s higher feeding rate to be the key factor underlying its advantage, without which it is possible to recapitulate the advantage of collective foraging in patchy environments. Our work highlights the theoretical advantage of collective foraging due to group formation alone without long-range interactions, and the valuable role of modelling to guide experiments.
Pharmacological inhibition of the heart of glass (HEG1)-Krev interaction trapped protein 1 (KRIT1) protein complex increases Krüppel-like Factors 4 and 2 (KLF4/2) expression in endothelial cells
Authors: Lopez-Ramirez Miguel Alejandro , Haynes Mark K. , Hale Preston , Oukoloff Killian , Bautista Matthew , Gongol Brendan , Shyy John Y. , Ballatore Carlo , Sklar Larry A. , Gingras Alexandre R. 
Published: August 2019

ABSTRACTThe Krüppel-like Factors 4 and 2 (KLF4/2) are transcription factors and master regulators of endothelial cells (ECs) phenotype and homeostasis. KLF4/2 are important blood-flow-responsive genes within ECs that differentially regulate the expression of factors that confer anti-inflammatory, antithrombotic, and antiproliferative effects in ECs. Genetic inactivation of endothelial KRIT1 (Krev interaction trapped protein 1) or HEG1 (Heart of glass) lead to upregulation of KLF4/2 expression levels. Furthermore, increased expression of thrombomodulin (THBD) and suppression of thrombospondin (THBS1) was ascribed to elevation of KLF4/2 as a result of loss of endothelial KRIT1. Here, we developed a high-throughput screening assay to identify inhibitors of the HEG1-KRIT1 interaction and identified, HEG1-KRIT1 inhibitor 1 (HKi1), as a promising hit inhibitor. The crystal structure of HKi1 bound to the KRIT1 FERM domain confirmed the primary screening results and ultimately led to the identification of a fragment-like inhibitor (HKi3), which occupies the HEG1 pocket producing comparable activity. These findings suggest that these inhibitors block the interaction by competing with the HEG1 for binding to KRIT1 FERM domain. Moreover, our results demonstrate that HKi3 upregulates KLF4/2 gene expression in two types of human ECs. These results reveal that acute pharmacological inhibition of the HEG1-KRIT1 interaction rapidly induces expression of KLF4/2 and their important transcriptional targets thrombomodulin and thrombospondin.
Open source computational simulation for a moth-inspired navigation algorithm
Authors: Benelli Noam , Gurka Roi , Golov Yiftach , Harari Ally , Zilman Gregory , Liberzon Alex 
Published: August 2019

AbstractOlfactory navigation in insects, for instance when males search for mates, is a navigational problem of a self-propelled agent with limited sensor capabilities in a scalar field (odor) convected and diffused by turbulent wind. There are numerous navigation strategies proposed to explain the navigation paths of insects to food (flowers) or mating partners (females). In a search for a mate, the males use airborne pheromone puffs in turbulent environments around trees and vegetation. It is difficult to compare the various strategies because of a lack of a single simulation framework that can change a single parameter in time and test all the strategies against a controlled environment. This work aims at closing this gap, suggesting an open source, freely accessible simulation framework, abbreviated MothPy. We implement the simulation framework using another open source package (“pompy”) that recreates a state-of-the-art puff-based odor plume model of Farrell et al. [1]. We add four different navigation strategies to the simulation framework based on and extending the previously published models [2, 3], and compare their performance with different wind and odor spread parameters. We test a sensitivity analysis of the navigation strategies to the plume meandering and to increased turbulence levels that are effectively expressed as the elevated puff spread rates. The simulations are compared statistically and provide an interesting view on the robustness and effectiveness of various strategies. This benchmarking-ready simulation framework could be useful for the biology-oriented, as well as engineering-oriented studies, assisting to deduce the evolutionary efficient strategies and improving self-propelled autonomous systems in complex environments.