bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of the sex-determination gene in tunas (Thunnus fishes)
Authors: Nakamura Yoji , Higuchi Kentaro , Kumon Kazunori , Yasuike Motoshige , Takashi Toshinori , Gen Koichiro , Fujiwara Atushi 
Published: June 2021

AbstractFish species have a variety of sex determination systems. Tunas (genus Thunnus) have an XY genetic sex-determination system. However, the Y chromosome or responsible locus has not yet been identified in males. In a previous study, a female genome of Pacific bluefin tuna (T. orientalis) was sequenced, and candidates for sex-associated DNA polymorphisms were identified by a genome-wide association study using resequencing data. In the present study, we sequenced a male genome of Pacific bluefin tuna by long-read and linked-read sequencing technologies, and explored male-specific loci through a comparison with the female genome. As a result, we found a unique region carrying the male-specific haplotype, where a homolog of estrogen sulfotransferase gene was predicted to be encoded. The genome-wide mapping of previously resequenced data indicated that, among the functionally annotated genes, only this gene, named sult1st6y, was paternally inherited in the males of Pacific bluefin tuna. We reviewed the RNA-seq data of southern bluefin tuna (T. maccoyii) in the public database and found that sult1st6y of southern bluefin tuna was expressed in all male testes, but absent or suppressed in the female ovary. Since estrogen sulfotransferase is responsible for the inactivation of estrogens, it is reasonable to assume that the expression of sult1st6y in gonad cells may inhibit female development, thereby inducing the individuals to become males. Thus, our results raise a promising hypothesis that sult1st6y is the sex-determination gene in Thunnus fishes, or at least functions at a crucial point in the sex-differentiation cascade.
A self-immolative linker for heparanase activatable probes
Authors: Schleyer Kelton A. , Liu Jun , Wang Zhishen , Cui Lina 
Published: June 2021

AbstractSubstrate-based probes utilize known substrate specificity parameters to create a probe that can be activated by a target enzyme. In developing probes for heparanase, an endo-ß-glucuronidase, we previously reported that small, inactive substrate-based probes could be electronically tuned by incorporating electron-withdrawing atoms on the aromatic aglycone fluorophore, ortho- to the cleaved glycosidic bond. However, the installation of electron-withdrawing groups directly onto established fluorophores or other reporters complicates the synthesis of new heparanase probes. In this work we report a new design strategy to expand the toolkit of heparanase imaging probes, in which the installation of an electronically tuned benzyl alcohol linker restored the activity of a previously inactive heparanase probe using 4-methylumbelliferone as the fluorescent reporter, suggesting such a linker can provide a scaffold for facile development of activatable heparanase probes bearing a variety of imaging moieties.
Norwegian Kveik brewing yeasts are adapted to higher temperatures and produce fewer off-flavours under heat stress than commercial Saccharomyces cerevisiae American Ale yeast
Authors: Kits Dimitri , Garshol Lars Marius 
Published: June 2021

AbstractNorwegian kveik are a recently described family of domesticated Saccharomyces cerevisiae brewing yeasts used by farmhouse brewers in western Norway for generations to produce traditional Norwegian farmhouse ale. Kveik ale yeasts have been domesticated by farmhouse brewers through serial repitching of the yeast in warm wort (>30°C) punctuated by long periods of dry storage. Kveik yeasts are alcohol tolerant, flocculant, capable of utilizing maltose/maltotriose, phenolic off flavour negative, and exhibit elevated thermotolerance when compared to other modern brewer’s yeasts belonging to the ‘Beer 1’ clade. However, the optimal fermentation and growth temperatures (Topt) for kveik ale yeasts and the influence of fermentation temperature of the production of flavour-active metabolites like fusel alcohols and sulfur compounds (H2S, SO2) are not known. Here we show that kveik ale yeasts have an elevated optimal fermentation temperature (Topt) when compared to commercial American Ale yeast (SafAle™ US-05) and that they produce fewer off-flavours at high temperatures (>30°C) when compared to commercial American Ale yeasts. The tested kveik yeasts show significantly higher maximum fermentation rates than American Ale yeast not only at elevated temperatures (>30°C), but also at ‘typical’ ale fermentation temperatures (20°C-25°C). Finally, we demonstrate that kveik ale yeasts are heterogeneous in their Topt and that they attenuate standard wort robustly above their Topt unlike our control American Ale yeast which showed very poor apparent attenuation in our standard wort at temperatures ≫ Topt. Our results provide further support that kveik yeasts may possess favourable fermentation kinetics and sensory properties compared to American Ale yeasts. The observations here provide a roadmap for brewers to fine tune their commercial fermentations using kveik ale yeasts for optimal performance and/or flavour impact.
Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis
Authors: Dingerdissen Hayley M , Vora Jeet , Cauley Edmund , Bell Amanda , King Charles Hadley , Mazumder Raja 
Published: June 2021

AbstractDespite accumulating evidence supporting a role for glycosylation in cancer progression and prognosis, the complexity of the human glycome and glycoproteome poses many challenges to understanding glycosylation-related events in cancer. In this study, a multifaceted genomics approach was applied to analyze the impact of differential expression of glycosyltransferases (GTs) in 16 cancers. An enzyme list was compiled and curated from numerous resources to create a consensus set of GTs. Resulting enzymes were analyzed for differential expression in cancer, and findings were integrated with experimental evidence from other analyses, including: similarity of healthy expression patterns across orthologous genes, miRNA expression, automatically-mined literature, curation of known cancer biomarkers, N-glycosylation impact, and survival analysis. The resulting list of GTs comprises 222 human enzymes based on annotations from five databases, 84 of which were differentially expressed in more than five cancers, and 14 of which were observed with the same direction of expression change across all implicated cancers. 25 high-value GT candidates were identified by cross-referencing multimodal analysis results, includingPYGM,FUT6and additional fucosyltransferases, several UDP-glucuronosyltransferases, and others, and are suggested for prioritization in future cancer biomarker studies. Relevant findings are available through OncoMX athttps://data.oncomx.org, and the overarching pipeline can be used as a framework for similarly analysis across diverse evidence types in cancer. This work is expected to improve the understanding of glycosylation in cancer by transparently defining the space of glycosyltransferase enzymes and harmonizing variable experimental data to enable improved generation of data-driven cancer biomarker hypotheses.
HKG: An open genetic variant database of 205 Hong Kong Cantonese exomes
Authors: Ou Min , Leung Henry Chi-Ming , Leung Amy Wing-Sze , Luk Ho-Ming , Yan Bin , Liu Chi-Man , Tong Tony Ming-For , Mok Myth Tsz-Shun , Ko Wallace Ming-Yuen , Law Wai-Chun , Lam Tak-Wah , Lo Ivan Fai-Man , Luo Ruibang 
Published: June 2021

AbstractHKG is the first fully accessible variant database for Hong Kong Cantonese, constructed from 205 novel whole-exome sequencing data. There has long been a research gap in the understanding of the genetic architecture of southern Chinese subgroups, including Hong Kong Cantonese. HKG detected 196,325 high-quality variants with 5.93% being novel, and 25,472 variants were found to be unique in HKG compared to other Chinese populations (CHN). PCA illustrates the uniqueness of HKG in CHN, and IBD analysis revealed that it is related mostly to southern Chinese with a similar effective population size. An admixture study estimated the ancestral composition of HKG and CHN, with a gradient change from north to south, consistent with their geological distribution. ClinVar, CIViC and PharmGKB annotated 599 clinically significant variants and 360 putative loss-of-function variants, substantiating our understanding of population characteristics for future medical development. Among the novel variants, 96.57% were singleton and 6.85% were of high impact. With a good representation of Hong Kong Cantonese, we demonstrated better variant imputation using reference with the addition of HKG data, thus successfully filling the data gap in southern Chinese to facilitate the regional and global development of population genetics.
Sticking around: plant persistence strategies on edaphic islands
Authors: Ottaviani Gianluigi , Méndez-Castro Francisco E. , Conti Luisa , Zelený David , Chytrý Milan , Doležal Jiři , Jandová Veronika , Altman Jan , Klimešová Jitka 
Published: June 2021

ABSTRACTSpecies extinction risk at local scales can be partially offset by strategies promoting in-situ persistence. We explored how persistence-related traits of clonal and non-clonal plants in temperate dry grasslands respond intra- and interspecifically to variation in environmental conditions (soil, climate) and insularity.We focused on edaphic island specialist species, hypothesizing that plants experiencing harsh soil environments and strong insularity are distinguished by traits supporting enhanced persistence, such as small stature, long lifespan and resource-conservative strategies. We used linear mixed-effect models and bivariate ordinary least squares linear models to explore the response of species triats to environmental and biogeographic predictors.We found general support for this hypothesis. Soil properties and insularity emerged as the most important drivers of trait patterns. However, clonal species showed more consistent responses to variation in environmental conditions and insularity than non-clonal plants, which were characterized by distinct species-specific responses.Soil properties and insularity confirmed their major role in shaping the persistence strategies of edaphic island plant species. These drivers may exert their effect on specific functions (e.g. belowground resource conservation captured by BDMC). Additionally, we unambiguously identified that clonal species had different persistence strategies than non-clonal ones.
The use of autologous skeletal muscle derived cells as a sling in the treatment of induced stress urinary incontinence, an experimental study
Authors: Wadie Bassem S. , Aamer Haytham G. , Khater Sherry M. , Gabr Mahmoud M. 
Published: June 2021

AbstractIntroduction & hypothesisThis is an experimental pre-clinical study testing for the applicability of autologous skeletal muscle derived cells as a seeded sling for the treatment of SUI in the canine modelMethods10 Mongrel dogs: In 4, skeletal muscle biopsy was harvested from Biceps Femoris. 1 month later, incontinence was induced in 8 dogs through surgical disruption of the pubourethral ligaments. Muscle biopsy was incubated in DMEM medium and after expansion for 8 weeks, MDCs were collected. PGA scaffold was immersed in culture medium, coated with matrigel and cells were seeded. The sling was placed suburethrally in 8 dogs; 2 of which were cell-seeded and 4 had the scaffold only.Urethral pressure (UP) measurement was done at baseline and 2 weeks alter insertion of the sling.The urethra with its surrounding was harvested 4 weeks after sling insertion for histopathology. 2 dogs were considered as control, in which no urethrolysis or insertion of slings were carried outResultsUP show increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 cmH20 (Median 23 cmH20)Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold, as demonstrated by Desmin. This was maximum in dogs # 1& 2. This was not the case in the 4 dogs that had PGA sling only.ConclusionThe use of skeletal muscle –seeded PGA scaffold is a practical technique with preserved integrity of histological differentiation in canine model at short term.Brief SummaryAutologous Skeletal muscle-derived cells could be propagated in vitro and seeded to PGS scaffolds and used as slings
Multivariate associations between dopamine receptor availability and risky investment decision making across adulthood
Authors: Green Mikella A. , Seaman Kendra L. , Crawford Jennifer L. , Kuhnen Camelia M. , Samanez-Larkin Gregory R. 
Published: June 2021

AbstractPharmacological manipulations have revealed that enhancing dopamine increases financial risk taking across adulthood. However, it is unclear whether baseline individual differences in dopamine function, assessed using PET imaging, are related to performance on risky financial decision making tasks. Here, thirty-five healthy adults completed an incentive-compatible learning-based risky investment decision task and a PET scan at rest using [11C]FLB457 to assess dopamine D2-like receptor availability. In the task, participants made choices between a safe asset (bond) and a risky asset (stock) with either an expected value less than the bond (“bad stock”) or expected value greater than the bond (“good stock”). Five measures of behavioral performance (choice inflexibility, risk seeking, suboptimal investment) and beliefs (absolute error, optimism) were extracted from the task data and average non-displaceable dopamine D2-like binding potential was extracted from four brain regions of interest (midbrain, amygdala, anterior cingulate, insula) from the PET imaging data. Given the presence of multiple independent and dependent variables, we used canonical correlation analysis (CCA) to evaluate multivariate associations between learning-based decision making and dopamine function controlling for age. Decomposition of the first dimension (r = .76) revealed that the strongest associations were between measures of choice inflexibility, incorrect choice, optimism, amygdala binding potential, and age. Follow-up univariate analyses revealed that amygdala binding potential and age were both independently associated with choice inflexibility. The findings reveal latent associations between baseline neural and behavioral measures suggesting that individual differences in dopamine function may be associated with learning-based financial risk taking in healthy adults.
Cryo-EM Structure of a Ferrichrome Importer FhuCDB
Authors: Hu Wenxin , Zheng Hongjin 
Published: June 2021

AbstractAs one of the most elegant biological processes developed in bacteria, the siderophore-mediated iron uptake demands the action of specific ATP-binding cassette (ABC) importers. Although extensive studies have been done on various ABC importers, the molecular basis of these iron-chelated-siderophore importers are still not fully understood. Here, we report the structure of a ferrichrome importer FhuCDB from Escherichia coli at 3.4Å resolution determined by cryo electron microscopy. The structure revealed a monomeric membrane subunit of FhuB with a substrate translocation pathway in the middle. In the pathway, there were unique arrangements of residues, especially layers of methionines. Important residues found in the structure were interrogated by mutagenesis and functional studies. Surprisingly, the importer’s ATPase activity was decreased upon FhuD binding, which deviated from the current understanding about bacterial ABC importers. In summary, our studies not only reveal a new structural twist in the type II ABC importer subfamily, but also provide biological insights in the transport of iron-chelated siderophores.
Validating marker-less pose estimation with 3D x-ray radiography
Authors: Moore Dalton D. , Walker Jeffrey D. , MacLean Jason N. , Hatsopoulos Nicholas G. 
Published: June 2021

ABSTRACTTo reveal the neurophysiological underpinnings of natural movement, neural recordings must be paired with accurate tracking of limbs and postures. Here we validate the accuracy of DeepLabCut (DLC) by comparing it to a 3D x-ray video radiography system that tracks markers placed under the skin (XROMM). We record behavioral data simultaneously with XROMM and high-speed video for DLC as marmosets engage in naturalistic foraging and reconstruct three-dimensional kinematics in a shared coordinate system. We find that DLC tracks position and velocity of 12 markers on the forelimb and torso with low median error (0.272 cm and 1.76 cm/s, respectively) corresponding to 2.9% of the full range of marker positions and 5.9% of the range of speeds. For studies that can accept this relatively small degree of error, DLC and similar marker-less pose estimation tools enable the study of more naturalistic, unconstrained behaviors in many fields including non-human primate motor control.Summary StatementWe validate the accuracy of DeepLabCut, a widely used marker-less pose estimation tool, using a marker-based 3D x-ray radiography system (XROMM).
Bioengineering a Miniaturized In Vitro 3D Myotube Contraction Monitoring Chip For Modelization of Muscular Dystrophies
Authors: Rose Nicolas , Sonam Surabhi , Nguyen Thao , Grenci Gianluca , Bigot Anne , Muchir Antoine , Ladoux Benoît , Le Grand Fabien , Trichet Léa 
Published: June 2021

ABSTRACTQuantification of skeletal muscle functional contraction is essential to assess the outcomes of therapeutic procedures for muscular disorders. Muscle three-dimensional “Organ-on-chip” models usually require a substantial amount of biological material, which is problematic in the context of limited patient sample. Here we developed a miniaturized 3D myotube culture chip with contraction monitoring capacity. Optimized micropatterned substrate design enabled to obtain high culture yields in tightly controlled microenvironments. Spontaneous contractions in myotubes derived from primary human myoblasts were observed. Analysis of nuclear morphology confirmed a similar organization between obtained myotubes and in vivo myofibers. LMNA-related Congenital Muscular Dystrophy (L-CMD) was modelled with successful development of mutant 3D myotubes displaying contractile dysfunction. This technology can thus be used to study contraction characteristics and evaluate how diseases affect muscle organization and force generation. Importantly, it requires significantly fewer starting materials than current systems, which should allow to substantially improve drug screening capability.
Rapid high-resolution structure analysis of small, biotechnologically relevant enzymes by cryo-electron microscopy
Authors: Dimos Nicole , Helmer Carl P.O. , Chánique Andrea M. , Wahl Markus C. , Kourist Robert , Hilal Tarek , Loll Bernhard 
Published: June 2021

ABSTRACTEnzyme catalysis has emerged as a key technology for developing efficient, sustainable processes in the chemical, biotechnological and pharmaceutical industries. Plants provide large and diverse pools of biosynthetic enzymes that facilitate complex reactions, such as the formation of intricate terpene carbon skeletons, with exquisite specificity. High-resolution structural analysis of these enzymes is crucial to understand their mechanisms and modulate their properties by targeted engineering. Although cryo-electron microscopy (cryo-EM) has revolutionized structural biology, its applicability to high-resolution structure analysis of comparatively small enzymes is so far largely unexplored. Here, we show that cryo-EM can reveal the structures of ~120 kDa plant borneol dehydrogenases at or below 2 Å resolution, paving the way for the fast development of new biocatalysts that provide access to bioactive terpenes and terpenoids.
Validating the Representational Space of Deep Reinforcement Learning Models of Behavior with Neural Data
Authors: Bruch Sebastian , McClure Patrick , Zhou Jingfeng , Schoenbaum Geoffrey , Pereira Francisco 
Published: June 2021

AbstractDeep Reinforcement Learning (Deep RL) agents have in recent years emerged as successful models of animal behavior in a variety of complex learning tasks, as exemplified by Song et al. [2017]. As agents are typically trained to mimic an animal subject, the emphasis in past studies on behavior as a means of evaluating the fitness of models to experimental data is only natural. But the true power of Deep RL agents lies in their ability to learn neural computations and codes that generate a particular behavior—factors that are also of great relevance and interest to computational neuroscience. On that basis, we believe that model evaluation should include an examination of neural representations and validation against neural recordings from animal subjects. In this paper, we introduce a procedure to test hypotheses about the relationship between internal representations of Deep RL agents and those in animal neural recordings. Taking a sequential learning task as a running example, we apply our method and show that the geometry of representations learnt by artificial agents is similar to that of the biological subjects’, and that such similarities are driven by shared information in some latent space. Our method is applicable to any Deep RL agent that learns a Markov Decision Process, and as such enables researchers to assess the suitability of more advanced Deep Learning modules, or map hierarchies of representations to different parts of a circuit in the brain, and help shed light on their function. To demonstrate that point, we conduct an ablation study to deduce that, in the sequential task under consideration, temporal information plays a key role in molding a correct representation of the task.
NNAL, a major metabolite of tobacco-specific carcinogen NNK, promotes lung cancer progression through deactivating LKB1 in an isomer-dependent manner
Authors: Bian Tengfei , Wang Yuzhi , Botello Jordy F. , Hu Qi , Jiang Yunhan , Zingone Adriana , Corral Pedro A. , Zahra Aly F. , Wu Yougen , Ryan Bríd M. , Jin Lingtao , Xing Chengguo 
Published: June 2021

AbstractSmoking is associated with worse clinical outcomes for lung cancer patients. Cell-based studies suggest that NNK (a tobacco specific carcinogen) promotes lung cancer progression. Given its short half-life, the physiological relevance of these in vitro results remains elusive. NNAL, a major metabolite of NNK with a similar structure, a chiral center, and a longer half-life, has never been evaluated in cancer cells. In this study, we characterized the effect of NNAL and its enantiomers on cancer progression among a panel of NSCLC cell lines and explored the associated mechanisms. We found that (R)-NNAL promotes cell proliferation, enhances migration, and induces drug resistance while (S)-NNAL has much weaker effects. Mechanistically, (R)-NNAL phosphorylates and deactivates LKB1 via the β-AR signaling in the LKB1 wild type NSCLC cell lines, contributing to the enhanced proliferation, migration, and drug resistance. Of note, NNK exposure also increases the phosphorylation of LKB1 in A/J mice. More importantly, human lung cancer tissues appear to have elevated LKB1 phosphorylation. Our results reveal, for the first time, that NNAL may promote lung cancer progression through LKB1 deactivation in an isomer-dependent manner.