bluuebunny/crossref_metadata_2025_split huggingface dataset:
scds: Computational Annotation of Doublets in Single Cell RNA Sequencing Data
Authors: Bais Abha S , Kostka Dennis 
Published: March 2019

AbstractMotivationSingle cell RNA sequencing (scRNA-seq) technologies enable the study of transcriptional heterogeneity at the resolution of individual cells and have an increasing impact on biomedical research. Specifically, high-throughput approaches that employ micro-fluidics in combination with unique molecular identifiers (UMIs) are capable of assaying many thousands of cells per experiment and are rapidly becoming commonplace. However, it is known that these methods sometimes wrongly consider two or more cells as single cells, and that a number of so-calleddoubletsis present in the output of such experiments. Treating doublets as single cells in downstream analyses can severely bias a study’s conclusions, and therefore computational strategies for the identification of doublets are needed. Here we present single cell doublet scoring (scds), a software tool for thein silicoidentification of doublets in scRNA-seq data.ResultsWithscds, we propose two new and complementary approaches for doublet identification: Co-expression based doublet scoring (cxds) and binary classification based doublet scoring (bcds). The co-expression based approach,cxds, utilizes binarized (absence/presence) gene expression data and employs a binomial model for the co-expression of pairs of genes and yields interpretable doublet annotations.bcds, on the other hand, uses a binary classification approach to discriminate artificial doublets from the original data. We apply our methods and existing doublet identification approaches to four data sets with experimental doublet annotations and find that our methods perform at least as well as the state of the art, but at comparably little computational cost. We also find appreciable differences between methods and across data sets, that no approach dominates all others, and we believe there is room for improvement in computational doublet identification as more data with experimental annotations becomes available. In the meanwhile,scdspresents a scalable, competitive approach that allows for doublet annotations in thousands of cells in a matter of seconds.Availability and Implementationscdsis implemented as an R package and freely available athttps://github.com/kostkalab/scds.Contactkostka@pitt.edu
The FluPRINT dataset: A multidimensional analysis of the influenza vaccine imprint on the immune system
Authors: Tomic Adriana , Tomic Ivan , Dekker Cornelia L. , Maecker Holden T. , Davis Mark M. 
Published: March 2019

AbstractRecent advances in machine learning have allowed identification of molecular and cellular factors that underly successful antibody responses to influenza vaccines. Results of these studies have revealed the high level of complexity necessary to establish influenza immunity, and many different cellular and molecular components involved. However, identified correlates of protection fail to account for the majority of vaccinated cases across ages, cohorts, and influenza seasons. Major challenges arise from small sample sizes and from analysis of only one aspect of the biology such by using transcriptome data. The objective of the current study is to create a unified database, entitled FluPRINT, to enable a large-scale study exploring novel cellular and molecular underpinnings of successful immunity to influenza vaccines. Over 3,000 parameters were considered, including serological responses to influenza strains, serum cytokines, cell subset phenotypes, and cytokine stimulations. FluPRINT, thus facilitates application of machine learning algorithms for data mining. The data are publicly available and represent a resource to uncover new markers and mechanisms that drive successful influenza vaccination.
Keratin-Based Epidermal Green Autofluorescence is a Common Biomarker of Organ Injury
Authors: Zhang Mingchao , Li Yujia , Wang Jiucun , Tang Huiru , Yang Zhong , Wu Danhong , Tao Yue , He Hao , Wang Sijia , Chen Xingdong , Yin Shankai , Shi Haibo , Wei Xunbin , Chu Tianqing , Tang Wanzhi , Maharjan Dhruba Tara , Yang Zhaoxia , Wang Yu , Jin Li , Ying Weihai 
Published: March 2019

AbstractIt is critical to discover biomarkers for non-invasive evaluation of the levels of inflammation and oxidative stress in human body - two key pathological factors in numerous diseases. Our study has indicated keratin 1-based epidermal autofluorescence (AF) as a biomarker of this type: Inducers of both inflammation and oxidative stress dose-dependently increased epidermal green AF with polyhedral structure in mice, with the AF intensity being highly associated with the dosages of the inducers. Lung cancer also induced increased epidermal green AF of mice, which was mediated by inflammation. Significant and asymmetrical increases in green AF intensity with polyhedral structure were found in the Dorsal Index Fingers’ skin of acute ischemic stroke (AIS) patients. While the AF intensity of the subjects with high risk for developing AIS, ischemic stroke patients in recovery phase and lung cancer patients was significantly higher than that of healthy controls, both AF intensity and AF asymmetry of these four groups were markedly lower than those of the AIS patients, which have shown promise for AIS diagnosis. Several lines of evidence have indicated K1 as an origin of the AF, e.g., K1 siRNA administration attenuated the oxidative stress-induced AF increase of mice. Collectively, our study has indicated K1-based epidermal AF as a biomarker for non-invasive evaluation of the levels of inflammation and oxidative stress in the body. These findings have established a basis for novel keratin’s AF-based biomedical imaging technology for non-invasive, efficient and economic diagnosis and screening of such inflammation- and oxidative stress-associated diseases as AIS.
Ticks Home in on Body Heat: A New Understanding of Ectoparasite Host-Seeking and Repellent Action
Authors: Carr Ann L. , Salgado Vincent L. 
Published: March 2019

AbstractTicks are second only to mosquitoes as vectors of disease to humans and animals. Commercial insect repellents reduce or prevent potentially infectious tick bites by disrupting tick host-seeking behavior. Tick host-seeking is mainly ascribed to the Haller’s organ, a complex sensory structure on the tick foreleg that detects odors, carbon dioxide and heat4–7, but these host-seeking mechanisms and the mechanism of their disruption by repellents are not well understood1,2. There is anecdotal evidence that ticks and other ectoparasites are attracted to heat, but it has never been demonstrated that they use radiant heat to detect hosts at a distance. In fact, previous attempts to do this have concluded that radiant heat is not used by ticks. Here we show thatAmblyomma americanumandDermacentor variabilisticks can sense and home in on a human from several meters away, guided by radiant heat sensed by the Haller’s organ, and specifically the capsule, a covered spherical pit organ. An aperture in the capsule cover confers directionality and highly reflective interior surfaces of the capsule provide high sensitivity. Low concentrations of the insect repellents DEET, picaridin, 2-undecanone, citronellal and nootkatone eliminate thermotaxis without affecting olfactory-stimulated host-seeking behavior. Our results demonstrate that the tick Haller’s organ capsule is a radiant heat sensor used in host-finding and that repellents disrupt this sense at concentrations that do not disrupt olfaction. We anticipate this discovery to significantly aid insect repellent research and development of innovative strategies for protection against ectoparasites and vector-borne disease.
Differential effects of diet and weight on taste responses in diet-induced obese mice
Authors: Ahart Zachary C. , Martin Laura E. , Kemp Bailey R. , Banik Debarghya Dutta , Roberts Stefan G.E. , Torregrossa Ann-Marie , Medler Kathryn F 
Published: March 2019

AbstractThe ever growing obesity epidemic has created a need to develop a better understanding of the underlying mechanisms responsible for this condition. Appetite and consumption are directly influenced by the taste system which determines if potential food items will be ingested or rejected. While previous studies have reported that obese individuals have reduced taste perception, the relationship between these processes is still poorly understood. Earlier work has demonstrated that diet-induced obesity (DIO) directly impairs taste responses, particularly for sweet stimuli. These deficits occurred in the cells located in the oral cavity as well as in the behavioral responses. However, it is not clear if these changes to the taste system are due to obesity or to the high fat diet exposure. The goal of the current study was to determine if diet or excess weight is responsible for the DIO induced taste deficits. Using a combination of live cell imaging, brief-access licking, immunohistochemistry and real-time PCR, we have found that diet and weight gain can each selectivity affect taste. Follow up experiments determined that two key signaling proteins, gustducin and phospholipase Cβ2, are significantly reduced in the high fat diet without weight gain and obese mice, identifying a potential mechanism for the reduced taste responsiveness to some stimuli. Our data indicate that the relationship between obesity and taste is complex and reveal that for some stimuli, diet alone can cause taste deficits, even without the onset of obesity.
Allele frequency distribution of SNPs associated with levels of Vitamin D-binding protein and 25-hydroxyvitamin D
Authors: Nizamutdinov Igor , Popov Yaroslav , Ilinsky Valery , Rakitko Alexander 
Published: March 2019

AbstractHaplotypes defined by rs7041/rs4588 in GC gene modulate 25-hydroxyvitamin D (25(OH)D) and vitamin D-binding protein (DBP) levels. To investigate the distributions of GC polymorphisms, the rs7041 and rs4588 allele and haplotypes frequencies were analyzed in samples from different Eurasian regions. The GC1S haplotype associated with high level of serum 25(OH)D had the maximum frequency in European populations (except Finish population). Such frequency distributions may be a result of adaptation to low solar insolation rate. Besides, there was a strong trend of increasing GC1F haplotype frequency from Europe (10-15%) to Siberia and Easter Asia (40-45%).
Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties
Authors: Dye Briana R. , Youngblood Richard L. , Oakes Robert S. , Kasputis Tadas , Clough Daniel W. , Nagy Melinda S. , Spence Jason R. , Shea Lonnie D. 
Published: March 2019

AbstractTissues derived from human pluripotent stem cell (hPSC) often represent early developmental time points. Yet, when transplanted into immunocompromised mice, these hPSC-derived tissues further mature, which has been enhanced with biomaterial scaffolds, gaining tissue structure and cell types similar to the native adult lung. Our goal was to define the physico-chemical biomaterial properties, including the polymer type, degradation, and pore interconnectivity of the scaffolds. Transplantation of human lung organoids (HLOs) on microporous poly(lactide-co-glycolide) (PLG) scaffolds or polycaprolactone (PCL) produced organoids that formed tube-like structures that resembled both the structure and cellular diversity of an adult lung airway. Microporous scaffolds formed from poly(ethylene glycol) (PEG) hydrogel scaffolds inhibit maturation and the HLOs remain as lung progenitors. The structures formed from cells that occupy multiple pores within the scaffold, and pore interconnectivity and polymer degradation contributed to the maturation. Finally, the overall size of the generated airway structure and the total size of the tissue was influenced by the material degradation rate. Collectively, these biomaterial platforms provide a set of tools to promote maturation of the tissues and to control the size and structure of the organoids.
The alternative reality of plant mitochondrial DNA
Authors: Kozik Alexander , Rowan Beth A. , Lavelle Dean , Berke Lidija , Eric Schranz M. , Michelmore Richard W. , Christensen Alan C. 
Published: March 2019

ABSTRACTPlant mitochondrial genomes are usually assembled and displayed as circular maps based on the widely-held assumption that circular genome molecules are the primary form of mitochondrial DNA, despite evidence to the contrary. Many plant mitochondrial genomes have one or more pairs of large repeats that can act as sites for inter- or intramolecular recombination, leading to multiple alternative genomic arrangements (isoforms). Most mitochondrial genomes have been assembled using methods that were unable to capture the complete spectrum of isoforms within a species, leading to an incomplete inference of their structure and recombinational activity. To document and investigate underlying reasons for structural diversity in plant mitochondrial DNA, we used long-read (PacBio) and short-read (Illumina) sequencing data to assemble and compare mitochondrial genomes of domesticated(Lactuca sativa)and wild(L. salignaandL. serriola)lettuce species. This allowed us to characterize a comprehensive, complex set of isoforms within each species and to compare genome structures between species. Physical analysis ofL. sativamtDNA molecules by fluorescence microscopy revealed a variety of linear, branched linear, and circular structures. The mitochondrial genomes forL. sativaandL. serriolawere identical in sequence and arrangement, and differed substantially fromL. saligna,indicating that the mitochondrial genome structure did not change during domestication. From the isoforms evident in our data, we inferred that recombination occurs at repeats of all sizes at variable frequencies. The differences in genome structure betweenL. salignaand the two other lettuce species can be largely explained by rare recombination events that rearrange the structure. Our data demonstrate that representations of plant mitochondrial DNA as simple, genome-sized circular molecules are not accurate descriptions of their true nature and that in reality plant mitochondrial DNA is a complex, dynamic mixture of forms.Data AvailabilityBioProject: Organellar genomes of cultivated and wild lettuce(Lactuca)varieties PRJNA508811https://www.ncbi.nlm.nih.gov/bioproject/508811and other accessions as indicated through the text and supplemental data.FundingNSF grant MCB-1413152 to ACC and support from UC Davis to RWM.
Comparing Time Series Transcriptome Data Between Plants Using A Network Module Finding Algorithm
Authors: Lee Jiyoung , Heath Lenwood S. , Grene Ruth , Li Song 
Published: March 2019

ABSTRACTComparative transcriptome analysis is the comparison of expression patterns between homologous genes in different species. Since most molecular mechanistic studies in plants have been performed in model species including Arabidopsis and rice, comparative transcriptome analysis is particularly important for functional annotation of genes in other plant species. Many biological processes, such as embryo development, are highly conserved between different plant species. The challenge is to establish one-to-one mapping of the developmental stages between two species. In this protocol, we solve this problem by converting the gene expression patterns into a co-expression network and then apply network module-finding algorithms to the cross-species co-expression network. We describe how to perform such analysis using bash scripts for preliminary data processing and R programming language, which implemented simulated annealing method for module finding. We also provide instructions on how to visualize the resulting co-expression networks across species.
Return of an apex predator to a suburban preserve triggers a rapid trophic cascade
Authors: Leempoel Kevin , Meyer Jordana , Hebert Trevor , Nova Nicole , Hadly Elizabeth A. 
Published: March 2019

ABSTRACTAbsence of apex predators simplifies food chains, leading to trophic degradation of ecosystems and diminution of the services they provide1. However, most predators do not coexist well with humans, which has resulted in a decline of carnivores and functional ecosystems worldwide2. In some instances, cryptic carnivores manage to survive amidst human settlements, finding refuge in small biological islands surrounded by urban landscapes. In such a system, we used two non-invasive data collection methods (camera trapping and fecal sampling) to investigate the multiannual relationship between predators and prey, and between competitors, through analysis of: (1) relative abundance and detection probability of species over time, (2) causal interactions via empirical dynamic modeling, (3) diet, and (4) diel activity patterns. All approaches show concordance in the results: the natural return of an apex predator, the puma (Puma concolor), triggered a trophic cascade, affecting the abundance and behavior of its main prey, subordinate predators and other prey in the studied system. Our study demonstrates that trophic recovery can occur rapidly following the return of a top predator, even in small protected areas in increasingly urbanized landscapes.
Principles and characteristics of biological assemblies in experimentally determined protein structures
Authors: Xu Qifang , Dunbrack Roland L. 
Published: March 2019

AbstractMore than half of all structures in the PDB are assemblies of two or more proteins, including both homooligomers and heterooligomers. Structural information on these assemblies comes from X-ray crystallography, NMR, and cryo-EM spectroscopy. The correct assembly in an X-ray structure is often ambiguous, and computational methods have been developed to identify the most likely biologically relevant assembly based on physical properties of assemblies and sequence conservation in interfaces. Taking advantage of the large number of structures now available, some of the most recent methods have relied on similarity of interfaces and assemblies across structures of homologous proteins.
Nanotubes effectively deliver siRNA to intact plant cells and protect siRNA against nuclease degradation
Authors: Demirer Gozde S. , Zhang Huan , Goh Natalie S. , Chang Roger , Landry Markita P. 
Published: March 2019

AbstractPost-transcriptional gene silencing (PTGS) is a powerful tool to understand and control plant metabolic pathways, which is central to plant biotechnology. PTGS is commonly accomplished through delivery of small interfering RNA (siRNA) into cells. While siRNA delivery has been optimized for mammalian systems, it remains a significant challenge for plants due to the plant cell wall. Standard plant siRNA delivery methods (Agrobacteriumand viruses) involve coding siRNA into DNA vectors, and are only tractable for certain plant species. Herein, we develop a nanotube-based platform for direct delivery of siRNA, and show high silencing efficiency in intact plant cells. We demonstrate that nanotubes successfully deliver siRNA and silence endogenous genes owing to effective intracellular delivery and nanotube-induced protection of siRNA from nuclease degradation. This study establishes that nanotubes, which are below the size exclusion limit of the plant cell wall, could enable a myriad of plant biotechnology applications that rely on RNA delivery.
Decreasing Serine Levels During Growth Transition Triggers Biofilm Formation inBacillus subtilis
Authors: Greenwich Jennifer , Reverdy Alicyn , Gozzi Kevin , Cecco Grace Di , Tashjian Tommy , Godoy-Carter Veronica , Chai Yunrong 
Published: March 2019

ABSTRACTBiofilm development inBacillus subtilisis regulated at multiple levels. While a number of known signals that trigger biofilm formation do so through the activation of one or more sensory histidine kinases, it was recently discovered that biofilm activation is also coordinated by sensing intracellular metabolic signals, including serine starvation. Serine starvation causes ribosomes to pause on specific serine codons, leading to a decrease in the translation rate ofsinR, which encodes a master repressor for biofilm matrix genes, and ultimately biofilm induction. How serine levels change in different growth stages, howB. subtilisregulates intracellular serine levels in response to metabolic status, and how serine starvation triggers ribosomes to pause on selective serine codons remain unknown. Here we show that serine levels decrease as cells enter stationary phase and that unlike most other amino acid biosynthesis genes, expression of serine biosynthesis genes decreases upon the transition into stationary phase. Deletion of the gene for a serine deaminase responsible for converting serine to pyruvate led to a delay in biofilm formation, further supporting the idea that serine levels are a critical intracellular signal for biofilm activation. Finally, we show that levels of all five serine tRNA isoacceptors are decreased in stationary phase compared to exponential phase. Interestingly, the three isoacceptors recognizing UCN serine codons are reduced to a much greater extent than the two that recognize AGC and AGU serine codons. Our findings provide evidence for a link between serine homeostasis and biofilm development inB. subtilis.IMPORTANCEInBacillus subtilis, biofilm formation is triggered in response to various environmental and cellular signals. It was previously proposed that serine limitation acts as a proxy for nutrient status and triggers biofilm formation at the onset of biofilm entry through a novel signaling mechanism caused by global ribosome pausing on selective serine codons. In this study, we revealed that serine levels decrease at the biofilm entry due to catabolite control and a shunt mechanism. We also show that levels of five serine tRNA isoacceptors are differentially decreased in stationary phase compared to exponential phase; three isoacceptors recognizing UCN serine codons are reduced much greater than the two recognizing AGC and AGU codons. This indicates a possible mechanism for selective ribosome pausing.
Emotion Modulation of the Body-Selective Areas in the Developing Brain
Authors: Ross Paddy , Gelder Beatrice de , Crabbe Frances , Grosbras Marie-Hélène 
Published: March 2019

AbstractEmotions are strongly conveyed by the human body and the ability to recognize emotions from body posture or movement is still developing through childhood and adolescence. To date, there are very few studies exploring how these behavioural observations are paralleled by functional brain development. Furthermore, there are currently no studies exploring the development of emotion modulation in these areas. In the current study, we used functional magnetic resonance imaging (fMRI) to compare the brain activity of 25 children (age 6-11), 18 adolescents (age 12-17) and 26 adults while they passively viewed short videos of angry, happy or neutral body movements. We observed that when viewing bodies generally, adults showed higher activity than children bilaterally in the body-selective areas; namely the extra-striate body area (EBA), fusiform body area (FBA), posterior superior temporal sulcus (pSTS) and amygdala (AMY). Adults also showed higher activity than adolescents, but only in right hemisphere body-selective areas. Crucially, however, we found that there were no age differences in the emotion modulation of activity in these areas. These results indicate, for the first time, that despite activity selective to body perception increasing across childhood and adolescence, emotion modulation of these areas in adult-like from 7 years of age.Conflict of InterestThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.