bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging a surrogate outcome to improve inference on a partially missing target outcome
Authors: McCaw Zachary R. , Gaynor Sheila M. , Sun Ryan , Lin Xihong 
Published: December 2020

AbstractSample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray) for leveraging information from a correlated surrogate outcome (e.g. expression in blood) to improve inference on a partially missing target outcome (e.g. expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Sprayjointly models the target and surrogate outcomes within a bivariate regression framework. Unobserved values of either outcome are treated as missing data. We describe and implement an expectation conditional maximization algorithm for performing estimation in the presence of bilateral outcome missingness. Sprayestimates the same association parameter estimated by standard eQTL mapping and controls the type I error even when the target and surrogate outcomes are truly uncorrelated. We demonstrate analytically and empirically, using simulations and GTEx data, that in comparison with marginally modeling the target outcome, jointly modeling the target and surrogate outcomes increases estimation precision and improves power.
Association versus Prediction: the impact of cortical surface smoothing and parcellation on brain age
Authors: Zeighami Yashar , Evans Alan C. 
Published: December 2020

AbstractAssociation and prediction studies of the brain target the biological consequences of aging and their impact on brain function. Such studies are conducted using different smoothing levels and parcellations at the preprocessing stage, on which their results are dependent. However, the impact of these parameters on the relationship between association values and prediction accuracy is not established. In this study, we used cortical thickness and its relationship with age to investigate how different smoothing and parcellation levels affect the detection of age-related brain correlates as well as brain age prediction accuracy. Our main measures were resel numbers - resolution elements - and age-related variance explained. Using these common measures enabled us to directly compare parcellation and smoothing effects in both association and prediction studies. In our sample of N=608 participants with age range 18-88, we evaluated age-related cortical thickness changes as well as brain age prediction. We found a negative relationship between prediction performance and correlation values for both parameters. Our results also quantify the relationship between delta age estimates obtained based on different processing parameters. Furthermore, with the direct comparison of the two approaches, we highlight the importance of correct choice of smoothing and parcellation parameters in each task, and how they can affect the results of the analysis in opposite directions.
Change point detection with multiple alternatives reveals parallel evaluation of the same stream of evidence along distinct timescales
Authors: Booras Alexa , Stevenson Tanner , McCormack Connor N. , Rhoads Marie E. , Hanks Timothy D. 
Published: December 2020

AbstractIn order to behave appropriately in a rapidly changing world, individuals must be able to detect when changes occur in that environment. However, at any given moment, there are a multitude of potential changes of behavioral significance that could occur. Here we investigate how knowledge about the space of possible changes affects human change point detection. We used a stochastic auditory change point detection task that allowed model-free and model-based characterization of the decision process people employ. We found that subjects can simultaneously apply distinct timescales of evidence evaluation to the same stream of evidence when there are multiple types of changes possible. Informative cues that specified the nature of the change led to improved accuracy for change point detection through mechanisms involving both the timescales of evidence evaluation and adjustments of decision bounds. These results establish three important capacities of information processing for decision making that any proposed neural mechanism of evidence evaluation must be able to support: the ability to simultaneously employ multiple timescales of evidence evaluation, the ability to rapidly adjust those timescales, and the ability to modify the amount of information required to make a decision in the context of flexible timescales.
Intein-assisted bisection mapping systematically splits proteins for Boolean logic and inducibility engineering
Authors: Ho Trevor Y. H. , Shao Alexander , Lu Zeyu , Savilahti Harri , Menolascina Filippo , Wang Lei , Dalchau Neil , Wang Baojun 
Published: December 2020

AbstractSplit inteins are powerful tools for seamless ligation of synthetic split proteins. Yet, their use remains limited because the already intricate split site identification problem is often complicated by the requirement of extein junction sequences. To address this, we augmented a mini-Mu transposon-based screening approach and devised the intein-assisted bisection mapping (IBM) method. IBM robustly revealed clusters of split sites on five proteins, converting them into AND or NAND logic gates. We further showed that the use of inteins expands functional sequence space for splitting a protein. We also demonstrated the utility of our approach over rational inference of split sites from secondary structure alignment of homologous proteins. Furthermore, the intein inserted at an identified site could be engineered by the transposon again to become partially chemically inducible, and to some extent enabled post-translational tuning on host protein function. Our work offers a generalizable and systematic route towards creating split protein-intein fusions and conditional inteins for protein activity control.
Loss of a subunit of vacuolar ATPase identifies unexpected biological signatures of reduced organelle acidificationin vivo
Authors: Lore Pottie , Wouter Van Gool , Michiel Vanhooydonck , Franz-Georg Hanisch , Geert Goeminne , Andreja Rajkovic , Paul Coucke , Patrick Sips , Bert Callewaert 
Published: December 2020

AbstractThe inability to maintain a strictly regulated endo(lyso)somal acidic pH through the proton-pumping action of the vacuolar-ATPases has been associated with various human diseases including heritable connective tissue disorders, neurodegenerative diseases and cancer. Multiple studies have investigated the pleiotropic effects of reduced acidificationin vitro, but the mechanisms elicited by impaired endo(lyso)somal acidificationin vivoremain poorly understood. Here, we show that loss ofatp6v1e1bin zebrafish leads to early mortality, associated with craniofacial dysmorphisms, vascular anomalies, cardiac dysfunction, hypotonia and epidermal structural defects, reminiscent of the phenotypic manifestations in cutis laxa patients carrying a defect in theATP6V1E1gene. Mechanistically, we found thatin vivogenetic depletion ofatp6v1e1bleads to N-glycosylation defects and reduced maturation of endosomal and lysosomal vesicles, but retains the hypoxia-mediated response. In order to gain further insights into the processes affected by aberrant organelle acidification, we performed an untargeted analysis of the transcriptome and metabolome in earlyatp6v1e1b-deficient larvae. We report multiple affected pathways including but not limited to oxidative phosphorylation, sphingolipid and fatty acid metabolism with profound defects in mitochondrial respiration. Taken together, our results identify new complex biological effects of reduced organelle acidificationin vivo, which likely contribute to the multisystemic manifestations observed in disorders caused by v-ATPase deficiency.
Can citizen science analysis of camera trap data be used to study reproduction? Lessons from Snapshot Serengeti program
Authors: Lucie Thel , Simon Chamaillé-Jammes , Léa Keurinck , Maxime Catala , Craig Packer , Huebner Sarah E. , Christophe Bonenfant 
Published: December 2020

AbstractEcologists increasingly rely on camera-trap data to estimate biological parameters such as population abundance. Because of the huge amount of data, the assistance of non-scientists is often sought after, but an assessment of the data quality is necessary. We tested whether volunteers data from one of the largest citizen science projects - Snapshot Serengeti - could be used to study breeding phenology. We tested whether the presence of juveniles (less than one or 12 months old) of species in the Serengeti: topi, kongoni, Grant’s gazelle, could be reliably detected by the “naive” volunteers vs. trained observers. We expected a positive correlation between the proportion of volunteers identifying juveniles and their effective presence within photographs, assessed by the trained observers.The agreement between the trained observers was good (Fleiss’ κ > 0.61 for juveniles of less than one and 12 month(s) old), suggesting that morphological criteria can be used to determine age. The relationship between the proportion of volunteers detecting juveniles less than a month old and their actual presence plateaued at 0.45 for Grant’s gazelle, reached 0.70 for topi and 0.56 for kongoni. The same relationships were much stronger for juveniles younger than 12 months, reaching 1 for topi and kongoni. The absence of individuals < one month and the presence of juveniles < 12 months could be reliably assumed, respectively, when no volunteer and when all volunteers reported a presence of a young. In contrast, the presence of very young individuals and the absence of juveniles appeared more difficult to ascertain from volunteers’ classification, given how the classification task was presented to them.Volunteers’ classification allows a moderately accurate but quick sorting of photograph with/without juveniles. We discuss the limitations of using citizen science camera-traps data to study breeding phenology, and the options to improve the detection of juveniles.
Lyophilized yeast powder for adjuvant free thermostable vaccine delivery
Authors: Kumar Ravinder , Kharbikar Bhushan N. 
Published: December 2020

AbstractThermolabile nature of commercially available vaccines necessitates their storage, transportation and dissemination under refrigerated condition. Maintenance of continuous cold chain at every step increases the final cost of vaccines. Any breach in the cold chain, even for a short duration results in the need to discard the vaccine. As a result, there is a pressing need for the development of thermostable vaccines. In this proof of concept study, we showed thatE. colicurli-GFP fusion protein remains stable in freeze-dried yeast powder for more than a 13 and 6 months when stored at 30 °C and 37 °C respectively. Stability of the heterologous protein remains unaffected during the process of heat-inactivation and lyophilization. The mass of lyophilized yeast powder remains almost unchanged during the entire period of storage. Expressed protein remains intact even after two cycles of freeze and thaws. The protease deficient strain appears ideal for the development of whole recombinant yeast-based vaccines. The cellular abundance of expressed antigen in dry powder after a year was comparable to freshly lyophilized cells. SEM microscopy showed the intact nature of cells in powdered form even after a year of storage at 30 °C. Observation made in this study showed that freeze-dry yeast powder can play a vital role in the development of thermostable vaccines.
Hypothalamic glucocorticoid receptor in CRF neurons is essential for HPA axis habituation to repeated stressor
Authors: Dournes Carine , Dine Julien , Lopez Juan-Pablo , Brivio Elena , Anderzhanova Elmira , Roeh Simone , Kuehne Claudia , Holzapfel Maria , Huettl Rosa-Eva , Stoffel Rainer , Tietze Lisa , Eggert Carola , Schieven Marcel , Jakovcevski Mira , Deussing Jan M. , Chen Alon 
Published: December 2020

Short abstractHabituation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated homotypic stressors is crucial for the organism’s well-being. Many physiological and psychological disorders are associated with HPA axis dysfunction. Here, we show that glucocorticoid receptors in CRF neurons of the hypothalamic paraventricular nucleus are essential for HPA habituation. By increasing inhibitory tone onto CRF neurons, glucocorticoid receptors led to essential cellular modulation and hypothalamic-pituitary-adrenal axis activation dampening, when re-exposed to the same stressor.
Clade GR and Clade GH Isolates in Asia Show Highest Amount of SNPs
Authors: Sengupta Antara , Hassan Sk. Sarif , Choudhury Pabitra Pal 
Published: December 2020

AbstractClades are monophyletic groups composed of a common ancestor and all its lineal descendants. As the propensity of virulence of a disease depends upon the type of clade the virus belongs to and it causes different fatality rates of disease in different countries, so the clade-wise analysis of SARS-CoV-2 isolates collected from different countries can illuminate the actual evolutionary relationships between them. In this study, 1566 SARS-CoV-2 genome sequences across ten Asian countries are collected, clustered, and characterized based on the clade they belong to. The isolates are compared to the Wuhan reference sequence (Accession no:MN996528.1) to identify the mutations that occurred at different protein regions. Structural changes in amino acids due to mutations lead to functional instability of the proteins. Detailed clade-wise functional assessments are carried out to quantify the stability and vulnerability of the mutations occurring in SARS-CoV-2 genomes which can shade light on personalized prevention and treatment of the disease and encourage towards the invention of clade-specific vaccines.
Reduced listener-speaker neural coupling underlies speech understanding difficulty in older adults
Authors: Liu Lanfang , Li Hehui , Ding Xiaowei , Zhou Qi , Gao Dingguo , Lu Chunming , Ding Guosheng 
Published: December 2020

AbstractAn increasing body of studies have highlighted the importance of listener-speaker neural coupling in successful speech communication. How this mechanism may change with normal aging and the association of this change with age-related decline in speech understanding remain unexplored. In this study, we scanned with fMRI a young and an older speaker telling real-life stories, and then played the audio recordings to groups of young (N = 28, aged 19-27y) and older adults (N = 27, aged 58-75y) during scanning, respectively. The older listeners understood the story worse than the young, and the advancing age of the older listeners was associated with poorer speech understanding. Compared to the young listener-speaker dyads, the older dyads exhibited weaker neural couplings in both linguistic and extra-linguistic areas. Moreover, within the older group, the listener’s age was negatively correlated with the overall strength of interbrain coupling, which in turn was associated with poorer speech understanding. These results reveal the deficits of older adults in achieving neural alignment with other brains, which may underlie the age-related decline in speech understanding.
The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions
Authors: Pichon Xavier , Moissoglu Konstadinos , Coleno Emeline , Wang Tianhong , Imbert Arthur , Peter Marion , Chouaib Racha , Walter Thomas , Mueller Florian , Zibara Kazem , Bertrand Edouard , Mili Stavroula 
Published: December 2020

AbstractRNA localization and local translation are important for numerous cellular functions. In mammals, a class of mRNAs localize to cytoplasmic protrusions in an APC-dependent manner, with roles during cell migration. Here, we investigated this localization mechanism. We found that the KIF1C motor interacts with APC-dependent mRNAs and is required for their localization. Live cell imaging revealed rapid, active transport of single mRNAs over long distances that requires both microtubules and KIF1C. Two color imaging directly showed single mRNAs transported by single KIF1C motors, with the 3’UTR being sufficient to trigger KIF1C-dependent RNA transport and localization. Moreover, KIF1C remained associated with peripheral, multimeric RNA clusters and was required for their formation. These results reveal an RNA transport pathway in mammalian cells, in which the KIF1C motor has a dual role both in transporting RNAs and in promoting their clustering within cytoplasmic protrusions. Interestingly, KIF1C also transports its own mRNA suggesting a possible feedback loop acting at the level of mRNA transport.
Topical heterogeneity in affective touch: Does it impact body image?
Authors: Cazzato Valentina , Sacchetti Sofia , Shin Shelby , Makdani Adarsh , Trotter Paula Diane , McGlone Francis 
Published: December 2020

AbstractRecent evidence suggests that altered responses to affective touch - a pleasant interoceptive stimulus associated with activation of the C-Tactile (CT) system, may contribute to the aetiology and maintenance of mental conditions characterised by body image disturbances (e.g., Anorexia Nervosa). Here, we investigated whether tactile pleasantness and intensity differ across body sites, and if individual differences in dysmorphic appearance concerns and body awareness might be associated to touch perceptions across body sites. To this end, we measured perceived pleasantness and intensity of gentle, dynamic stroking touches applied to the palm, forearm, face, abdomen and back of 30 female participants (mean age: 25.87±1.17yrs) using CT-optimal (3 cm/s) and non-CT optimal (0.3 and 30 cm/s) stroking touch. As expected, participants rated CT-targeted touch as more pleasant compared to the two non-CT optimal stroking touch at all body sites. Nevertheless, CT-targeted touch applied to the abdomen elicited the lowest pleasantness ratings compared to all other body sites and to the two non-CT optimal stroking touch. Individual differences in body awareness and dysmorphic concerns significantly predicted preference for CT-optimal over non-CT optimal stroking touch applied to the forearm and the back. These findings begin to elucidate the link between CT sensitivity, dysmorphic appearance concerns and body awareness, which may have implications for future research looking to inform early interventions. Addressing impaired processing of affective interoceptive stimuli, such as CT-targeted touch, may be the key to current treatment approaches available for those populations at risk of disorders characterised by body image disturbance.
Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms
Authors: Rosenthal Sun Hee , Gerasimova Anna , Ma Charles , Li Hai-Rong , Grupe Andrew , Chong Hansook , Acab Allan , Smolgovsky Alla , Owen Renius , Elzinga Christopher , Chen Rebecca , Sugganth Daniel , Freitas Tracey , Graham Jennifer , Champion Kristen , Bhattacharya Anindya , Racke Frederick , Lacbawan Felicitas 
Published: December 2020

AbstractIdentification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. However, due to lack of standard NGS protocols, the application of NGS for hematologic malignancies into clinical settings remains limited. We report development and validation of a 48-gene NGS panel for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), andFLT3internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n=2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9-99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n=2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms.
Effects of ploidy and salmonid alphavirus infection on the skin and gill microbiome of Atlantic salmon (Salmo salar)
Authors: Brown Ryan , Moore Lindsey , Mani Amir , Patel Sonal , Salinas Irene 
Published: December 2020

AbstractThe microbial communities that live in symbiosis with the mucosal surfaces of animals provide the host with defense strategies against pathogens. These microbial communities are largely shaped by the environment and the host genetics. Triploid Atlantic salmon (Salmo salar) are being considered for aquaculture as they are reproductively sterile and thus cannot contaminate the natural gene pool. It has not been previously investigated how the microbiome of triploid salmon compares to that of their diploid counterparts. In this study, we compare the steady-state skin and gill microbiome of both diploid and triploid salmon, and determine the effects of salmonid alphavirus 3 experimental infection on their microbial composition. Our results show limited differences in the skin-associated microbiome between triploid and diploid salmon, irrespective of infection. In the gills, we observed a high incidence of the bacterial pathogenCandidatus Branchiomonas, with higher abundance in diploid compared to triploid control fish. Diploid salmon infected with SAV3 showed greater histopathological signs of epitheliocystis compared to controls, a phenomenon not observed in triploid fish. Our results indicate that ploidy can affect the alpha diversity of the gills but not the skin-associated microbial community. Importantly, during a natural outbreak ofBranchiomonas sp. the gill microbiome of diploid Atlantic salmon became significantly more dominated by this pathogen than in triploid animals. Thus, our results suggest that ploidy may play a role on Atlantic salmon gill health and provide insights into co-infection with SAV3 andC. Branchiomonasin Atlantic salmon.