bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of non-modelDrosophilaspecies to study natural variation in TOR pathway signaling
Authors: Steenwinkel Tessa E. , Hamre Kailee K. , Werner Thomas 
Published: June 2022

AbstractNutrition and growth are strongly linked, but not much is known about how nutrition leads to growth. To understand the connection between nutrition through the diet, growth, and proliferation, we need to study the phenotypes resulting from the activation and inhibition of central metabolic pathways. One of the most highly conserved metabolic pathways across eukaryotes is the Target of Rapamycin (TOR) pathway, whose primary role is to detect the availability of nutrients and to either induce or halt cellular growth. Here we used the model organismDrosophila melanogaster(D. mel.) and three non-modelDrosophilaspecies with different dietary needs,Drosophila guttifera(D. gut.),Drosophila deflecta(D. def.), andDrosophila tripunctata(D. tri.), to study the effects of dietary amino acid availability on fecundity and longevity. In addition, we inhibited the Target of Rapamycin (TOR) pathway, using rapamycin, to test how the inhibition interplays with the nutritional stimuli in these four fruit fly species. We hypothesized that the inhibition of the TOR pathway would reverse the phenotypes observed under conditions of overfeeding. Our results show that female fecundity increased with higher yeast availability in all four species but decreased in response to TOR inhibition. The longevity data were more varied: most species experienced an increase in median lifespan in both genders with an increase in yeast availability, while the lifespan ofD. mel.females decreased. When exposed to the TOR inhibitor rapamycin, the life spans of most species decreased, except forD. tri,while we observed a major reduction in fecundity across all species. The obtained data can benefit future studies on the evolution of metabolism by showing the potential of using non-model species to track changes in metabolism. Particularly, our data show the possibility to use relatively closely relatedDrosophilaspecies to gain insight on the evolution of TOR signaling.
Comparative genomics support reduced-genome Paraburkholderia symbionts of Dictyostelium discoideum amoebas are ancestrally adapted professional symbionts
Authors: Noh Suegene , Capodanno Benjamin J. , Xu Songtao , Hamilton Marisa C. , Strassmann Joan E. , Queller David C. 
Published: June 2022

AbstractThe social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. In addition, there is a large difference in genome size between P. agricolaris (8.7 million base pairs) vs. P. hayleyella and P. bonniea (4.1 Mbp) and in GC content (62% vs. 59%). We took a comparative genomics approach and compared the three genomes of D. discoideum-symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the two reduced genomes of P. bonniea and P. hayleyella display characteristics that support evolution in a host environment. In addition, all three D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Ultimately, our combined evidence supports that the reduced-genome D. discoideum-symbionts have evolved to be professional symbionts ancestrally adapted to their protist hosts.
Castration alters the circadian clock and Ucp1 expression in subcutaneous white adipose tissue of mice
Authors: Otsuka Tsuyoshi , Onishi Hiroki , Suzuki Mao , Marusawa Mami 
Published: June 2022

AbstractCastration increases the risk of metabolic syndromes in mammals. In addition, recent studies have demonstrated that castration increases the expression of Ucp1 in subcutaneous white adipose tissue (scWAT). However, how castration leads to thermogenic aberration remains poorly understood. Here, we found that castrated mice showed elevated Ucp1 expression in scWAT in response to cold exposure with an increase in body temperature in the light phase and a reduction in body weight gain with fat reduction despite showing no alterations in food intake, locomotor activity in a novel environment, and gastrocnemius muscle weight. We also analyzed the circadian behavioral rhythm and the expression rhythm of clock genes in the suprachiasmatic nucleus (SCN) and scWAT. We found that castrated mice showed fluctuations in circadian locomotor activity and a decrease in the expression rhythm of clock genes in the SCN (clock) and scWAT (Bmal1 and Per2). Moreover, the expression of Ucp1 in scWAT was rhythmic, and it was increased in castrated mice, while the expression of clock genes was decreased. These results indicate that castration may impact browning in scWAT through variations in the circadian clock and Ucp1 expression.
Compositional shifts associated with major evolutionary transitions in plants
Authors: Smith Stephen A. , Walker-Hale Nathanael , Parins Fukuchi C. Tomomi 
Published: June 2022

SummaryHeterogeneity in gene trees, morphological characters, and composition has been associated with several major clades across the plant tree of life. Here, we examine heterogeneity in composition across a large transcriptomic dataset of plants in order to better understand whether locations of shifts in composition are shared across gene regions and whether directions of shifts within clades are shared across gene regions.We estimate mixed models of composition for both DNA and amino acids across a recent large scale transcriptomic dataset for plants.We find shifts in composition across both DNA and amino acid datasets, with more shifts detected in DNA. We find that Chlorophytes and lineages within experience the most shifts. However, many shifts occur at the origins of land, vascular, and seed plants. While genes in these clades do not typically share the same composition, they tend to shift in the same direction. We discuss potential causes of these patterns.Compositional heterogeneity has been highlighted as a potential problem for phylogenetic analysis, but the variation presented here highlights the need to further investigate these patterns for the signal of biological processes.Plain language summaryWe demonstrate that many nucleotide and amino acid compositional shifts in plants occur at the origins of major clades and while individual genes do not share the same composition they often shift in the same direction. We suggest that these patterns warrant further exploration as the signal of important biological processes during the evolution of plants.
A computationally-enhanced hiCLIP atlas reveals Staufen1 RNA binding features and links 3’ UTR structure to RNA metabolism
Authors: Chakrabarti Anob M. , Iosub Ira A. , Lee Flora C. Y. , Ule Jernej , Luscombe Nicholas M. 
Published: June 2022

ABSTRACTThe structure of mRNA molecules plays an important role in its interactions with trans-acting factors, notably RNA binding proteins (RBPs), thus contributing to the functional consequences of this interplay. However, current transcriptome-wide experimental methods to chart these interactions are limited by their poor sensitivity. Here we extend the hiCLIP atlas of duplexes bound by Staufen1 (STAU1) ∼10-fold, through careful consideration of experimental assumptions, and the development of bespoke computational methods which we apply to existing data. We present Tosca, a Nextflow computational pipeline for the processing, analysis and visualisation of proximity ligation sequencing data generally. We use our extended duplex atlas to discover insights into the RNA selectivity of STAU1, revealing the importance of structural symmetry and duplex-span-dependent nucleotide composition. Furthermore, we identify heterogeneity in the relationship between STAU1-bound 3’ UTRs and metabolism of the associated RNAs that we relate to RNA structure: transcripts with short-range proximal 3’ UTR duplexes have high degradation rates, but those with long-range duplexes have low rates. Overall, our work enables the integrative analysis of proximity ligation data delivering insights into specific features and effects of RBP-RNA structure interactions.
AUF-1 knock down in mice overarches butyrate driven hypo-cholesteraemia by conjuring AUF-1-Dicer-1-miR122 hierarchy
Authors: Das Oishika , Kundu Jayanta , Ghosh Atanu , Gautam Anupam , Ghosh Souradeepa , Chakraborty Mainak , Masid Aaheli , Gauri Samiran Sona , Mitra Debmalya , Dutta Moumita , Mukherjee Budhaditya , Sinha Surajit , Bhaumik Moumita 
Published: June 2022

AbstractThis discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance. Hepatic miR122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of miR122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model. We showed that butyrate treatment caused upregulation of RNA-binding protein, AUF-1 resulting in RNase-III nuclease, Dicer-1 instability, and significant diminution of miR122. We proved its importance of AUF-1 and sequential downstream players in AUF-1-knock-down mice. We synthesized unique self-transfecting GMO (guanidinium-morpholino-oligonucleotides) linked PMO (Phosphorodiamidate-Morpholino Oligonucleotides)-based antisense reagent and injection of which in mouse caused near absence of AUF-1 coupled with increased Dicer-1 and miR122, and reduced serum cholesterol regardless of butyrate treatment indicating that butyrate acts though AUF-1. The roster of intracellular players was as follows: AUF-1-Dicer-1-miR122 for triggering butyrate driven hypocholesterlaemia. To our knowledge this is the first report linking AUF-1 with cholesterol biogenesis.
Early-Stage NSCLC Patients’ Prognostic Prediction with Multi-information Using Transformer and Graph Neural Network Model
Authors: Lian Jie , Deng Jiajun , Hui Sai Kam , Koohi-Moghadam Mohamad , She Yunlang , Chen Chang , Vardhanabhuti Varut 
Published: June 2022

AbstractBackgroundWe proposed a population graph with Transformer-generated and clinical features for the purpose of predicting overall survival and recurrence-free survival for patients with early-stage NSCLC and to compare this model with traditional models.MethodsThe study included 1705 patients with lung cancer (stage I and II), and a public dataset for external validation (n=127). We proposed a graph with edges representing non-imaging patient characteristics and nodes representing imaging tumour region characteristics generated by a pretrained Vision Transformer. The model was compared with a TNM model and a ResNet-Graph model. To evaluate the models’ performance, the area under the receiver operator characteristic curve (ROC-AUC) was calculated for both overall survival (OS) and recurrence-free survival (RFS) prediction. The Kaplan–Meier method was used to generate prognostic and survival estimates for low- and high-risk groups, along with net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). An additional subanalysis was conducted to examine the relationship between clinical data and imaging features associated with risk prediction.ResultsOur model achieved AUC values of 0·785 (95 % CI:0·716 - 0·855) and 0·695 (95 % CI:0·603 - 0·787) on the testing and external datasets for OS prediction, and 0·726 (95 % CI:0·653 - 0·800) and 0·700 (95 % CI:0·615 - 0·785) for RFS prediction. Additional survival analyses indicated that our model outperformed the present TNM and ResNet-Graph models in terms of net benefit for survival prediction.ConclusionOur Transformer-Graph model was effective at predicting survival in patients with early-stage lung cancer, which was constructed using both imaging and non-imaging clinical features. Some high-risk patients were distinguishable by using a similarity score function defined by non-imaging characteristics such as age, gender, histology type, and tumour location, while Transformer-generated features demonstrated additional benefits for patients whose non-imaging characteristics were non-discriminatory for survival outcomes.FundingThere was no funding source for this study.
Estimating the cumulative impact and zone of influence of anthropogenic features on biodiversity
Authors: Niebuhr Bernardo Brandão , Van Moorter Bram , Stien Audun , Tveraa Torkild , Strand Olav , Langeland Knut , Sandström Per , Alam Moudud , Skarin Anna , Panzacchi Manuela 
Published: June 2022

AbstractThe concept of cumulative impacts is widespread in policy documents, regulations, and ecological studies, but quantification methods are still evolving. Infrastructure development usually takes place in landscapes with preexisting anthropogenic features. Typically, their impact is determined by computing the distance to the nearest feature only, thus ignoring the potential cumulative impacts of multiple features. We propose thecumulative ZOI approachto assess whether and to what extent anthropogenic features lead to cumulative impacts.The approach estimates both effect size and zone of influence (ZOI) of anthropogenic features and allows for estimation of cumulative effects of multiple features distributed in the landscape. First, we use simulations and an empirical study to understand under which circumstances cumulative impacts arise. Second, we demonstrate the approach by estimating the cumulative impacts of tourist infrastructure in Norway on the habitat of wild reindeer (Rangifer t. tarandus), a nearly-threatened species highly sensitive to anthropogenic disturbance.Simulations show that analyses based on the nearest feature and our cumulative approach are indistinguishable in two extreme cases: when features are few and scattered and their ZOI is small, and when features are clustered and their ZOI is large. Empirical analyses revealed cumulative impacts of private cabins and tourist resorts on reindeer, extending up to 10 and 20 km, with different decaying functions. Although the impact of an isolated private cabin was negligible, the cumulative impact of ‘cabin villages’ could be much larger than that of a single large tourist resort. Focusing on the nearest feature only underestimates the impact of ‘cabin villages’ on reindeer.The suggested approach allows us to quantify the magnitude and spatial extent of cumulative impacts of point, linear, and polygon features in a computationally efficient and flexible way and is implemented in theoneimpactR package. The formal framework offers the possibility to avoid widespread underestimations of anthropogenic impacts in ecological and impact assessment studies and can be applied to a wide range of spatial response variables, including habitat selection, population abundance, species richness and diversity, community dynamics, and other ecological processes.
Life cycle exposure to cyhalofop-butyl induced reproductive toxicity toward zebrafish
Authors: Zhu Tao , Wang Siwen , Li Dong 
Published: June 2022

AbstractCyhalofop-butyl (CyB) is an herbicide widely used in paddy fields, which may transfer to aquatic ecosystems and cause harm to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to CyB (0.1, 1 and 10 ug/L) related to the environment throughout its adult life cycle from embryo to sexual maturity. The effects of CyB on zebrafish growth, reproduction and offspring development were studied. It was found that female spawning was inhibited and adult male fertility decreased. In addition, we detected the expression of sex steroid hormones and genes related to hypothalamus-pituitary-gonad-liver (HPGL) axis. After 150days of exposure, the hormone balance of parent zebrafish (F0) was disturbed and the concentrations of 17β-estradiol (E2) and vitellogenin (VTG) in zebrafish were decreased. F1 embryos showed abnormal developmental results, including decreased heart rate, decreased body length, spontaneous motor inhibition, while the developmental abnormalities of F1 embryos were relieved when exposed to CyB-free clear water. The change of sex hormone is regulated by gene expression related to HPGL axis. These results confirmed that long-term exposure to CyB in the environmental concentrations can damage the reproductive capacity of F0 generation zebrafish by disrupting the transcription of genes related to HPGL axis, which may lead to abnormal development of F1. Overall, these data may provide a new understanding of the reproductive toxicity of zebrafish parents and offspring after long-term exposure to CyB.HighlightsEnvironmental level of CyB exposure caused gonadal impairment.CyB exposure suppressed spawning ability of zebrafish.CyB exposure changed the plasma hormone level of zebrafish and altered HPGL axis in both genders.Parental CyB exposure led to abnormal development of F1.
An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite
Authors: Msosa Chimwemwe , Abdalrahman Tamer , Franz Thomas 
Published: June 2022

AbstractThe invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics.A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa).For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 ×10-18and 1.40 ×10-17J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 ×10-18and 0.70 ×10-17J for 4% and 51% areal strain.The current study demonstrated the developed model’s feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.
Understanding the Dynamics of Fluid-Structure Interaction with an Air Deflected Microfluidic Chip (ADMC)
Authors: ten Pas Chad , Du Ke , Pan Long , Wang Ruo-Qian , Xu Shiyou 
Published: June 2022

AbstractA deformable microfluidic system and a fluidic dynamic model have been successfully coupled to understand the dynamic fluid-structure interaction in transient flow, designed to understand the dentine hypersensitivity caused by hydrodynamic theory. The Polydimethylsiloxane thin sidewalls of the microfluidic chip are deformed with air pressure ranging from 50 to 500 mbar to move the liquid meniscus in the central liquid channel. The displacement is recorded and compared with our new theoretical model derived from the unsteady Bernoulli equation. We show that our theoretical model can well predict the ending point of the liquid displacement as well as the dynamics process, regardless of the wall thickness. Moreover, an overshooting and oscillation phenomenon is observed by reducing the friction factor by a few orders which could be the key to explain the dentine hypersensitivity caused by the liquid movement in the dentine tubules.
A small H2O-soluble ingredient of royal jelly lower cholesterol levels in liver cells by suppressing squalene epoxidase
Authors: Wang Chi , Jiang Zhen-yu , Wang Jing , Liu Jia-xin , Nian Yuan-yuan , Lixia-Liu  , Dang Tong , Meng Xian-mei 
Published: June 2022

AbstractExcessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the effectivity of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active ingredient of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction < 10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active ingredient of RJ in this action is < 10kDa in water-soluble form.
Analysis of the CYP1A2 caffeine metabolism gene in the student population at Lake Superior State University
Authors: Pittsley Rebekka A , Kolomyjec Stephen H 
Published: June 2022

Abstract85% of Americans drink caffeinated beverages on a daily basis. Each individual responds differently to caffeine depending on age, gender, diet, and ethnicity. Caffeinated beverages cause insomnia in some people, but not in others due to differences in the rate of caffeine metabolism. This study examines the variation in the caffeine metabolism of Lake Superior State University (LSSU) students. My hypothesis was that LSSU student allele frequencies would match those of the general population: 47.5% fast, 41.0% medium, and 11.5% slow caffeine metabolism. 200 LSSU students were sampled via buccal swabs. DNA was successfully isolated from 164 samples. Participants filled out a demographic questionnaire entailing caffeine intake, ethnicity, and sex. The CYP1A2 gene was amplified via standard PCR prior to genotyping by restriction digest and gel electrophoresis. The APAI restriction enzyme was used to determine the genotype of the rs762551 single nucleotide polymorphism (SNP), while the SACI enzyme was used as a positive digestion control. Overall, results showed a total of 42.7% fast, 44.5% medium, and 12.8% slow metabolizers. Of special note is that 24 of the 164 students sampled were of Native American heritage, an important yet underrepresented group in human genomics. This study provides the first reported look at the CYP1A2 variation within this North American subpopulation with metabolism rates being 50% fast, 33.3% medium, and 16.7% slow. The results confirm my initial hypothesis that the variation of caffeine metabolism gene frequencies for the LSSU student population would be representative of published allele frequencies for the general population.