bluuebunny/crossref_metadata_2025_split huggingface dataset:
A MademoiseLLE domain binding platform links the key RNA transporter to endosomes
Authors: Devan Senthil-Kumar , Schott-Verdugo Stephan , Müntjes Kira , Bismar Lilli , Reiners Jens , Hachani Eymen , Schmitt Lutz , Höppner Astrid , Smits Sander HJ , Gohlke Holger , Feldbrügge Michael 
Published: October 2021

AbstractSpatiotemporal expression can be achieved by transport and translation of mRNAs at defined subcellular sites. An emerging mechanism mediating mRNA trafficking is microtubule- dependent co-transport on shuttling endosomes. Although progress has been made in identifying various components of the endosomal mRNA transport machinery, a mechanistic understanding of how these RNA-binding proteins are connected to endosomes is still lacking. Here, we demonstrate that a flexible MademoiseLLE (MLLE) domain platform within RNA- binding protein Rrm4 ofUstilago maydisis crucial for endosomal attachment. Our structure/function analysis uncovered three MLLE domains at the C-terminus of Rrm4 with a functionally defined hierarchy. MLLE3 recognises two PAM2-like sequences of the adaptor protein Upa1 and is essential for endosomal shuttling of Rrm4. MLLE1 and MLLE2 are most likely accessory domains exhibiting a variable binding mode for interaction with currently unknown partners. Thus, endosomal attachment of the mRNA transporter is orchestrated by a sophisticated MLLE domain binding platform.
CircSry regulates spermatogenesis by enhancing γH2AX expression via sponging miR-138-5p
Authors: Song Yanze , Chen Min , Zhang Yingfan , Li Na , Chen Min , Qiao Miaomiao , Cao Yuanwei , Chen Jian , Gao Fei , Wang Haoyi 
Published: October 2021

AbstractSry on the Y chromosome is the master switch in sex determination in mammals. It has been well established that Sry encodes a transcription factor that is transiently expressed in somatic cells of male gonad, inducing a series of events that lead to the formation of testes. In the testis of adult mice, Sry is expressed as a circular RNA (circRNA) transcript, a type of noncoding RNA that forms a covalently linked continuous loop. However, the physiological function of this Sry circRNA (circSry) remains unknown since its discovery in 1993. Here we show that circSry is mainly expressed in the spermatocytes, but not in mature sperms and Sertoli cells. Loss of circSry led to the reduction of sperm number and the defect of germ cell development. The expression of γH2AX was decreased and failure of XY body formation was noted in circSry KO germ cells. Further study demonstrates that circSry regulates H2AX mRNA indirectly in pachytene spermatocytes through sponging miR-138-5p. Our study demonstrates that, in addition to its well-known sex-determination function, Sry also plays important role in spermatogenesis as a circRNA.
Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy
Authors: Zou Yan , Zhang Miaomiao , Wu Qiongfeng , Zhao Ning , Chen Minwei , yang Cui , Du Yimei , Han Bing 
Published: October 2021

AbstractPrevious studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is expressed in hearts and implicated in cardiac remodeling and cardiac dysfunction. However, the effects of TRPV4 on pressure overload-induced cardiac hypertrophy remain unclear. In this study, we found that TRPV4 expression was significantly increased in mouse hypertrophic hearts, human failing hearts, and neurohormone-induced hypertrophic cardiomyocytes. Deletion of TRPV4 attenuated transverse aortic constriction (TAC)-induced cardiac hypertrophy, cardiac dysfunction, fibrosis, inflammation, and the activation of NFκB - NOD-like receptor pyrin domain-containing protein 3 (NLRP3) in mice. In vitro, TRPV4 inhibition decreased the neurohormone-induced cardiomyocyte hypertrophy and the increase of intracellular Ca2+ concentration. TRPV4 agonist triggered Ca2+ influx and evoked the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) but these effects were abolished by removing extracellular Ca2+ or TRPV4 inhibition. More importantly, TAC or neurohormone stimulation-induced CaMKII phosphorylation was significantly blocked by TRPV4 inhibition. Finally, we showed that CaMKII inhibition significantly inhibited the phosphorylation of NFκB induced by TRPV4 activation. Our results suggest that TRPV4 activation contributed to pressure overload-induced cardiac hypertrophy. This effect was associated with upregulated Ca2+/ CaMKII mediated the activation of NFκB-NLRP3. Thus, TRPV4 may represent a potential therapeutic drug target for cardiac hypertrophy.
A generalizable deep learning framework for inferring fine-scale germline mutation rate maps
Authors: Fang Yiyuan , Deng Shuyi , Li Cai 
Published: October 2021

AbstractGermline mutation rates are essential for genetic and evolutionary analyses. Yet, estimating accurate fine-scale mutation rates across the genome is a great challenge, due to relatively few observed mutations and intricate relationships between predictors and mutation rates. Here we present MuRaL (Mutation Rate Learner), a deep learning framework to predict mutation rates at the nucleotide level using only genomic sequences as input. Harnessing human germline variants for comprehensive assessment, we show that MuRaL achieves better predictive performance than current state-of-the-art methods. Moreover, MuRaL can build models with relatively few training mutations and a moderate number of sequenced individuals, and can leverage transfer learning to further reduce data and time demands. We apply MuRaL to produce genome-wide mutation rate maps for four representative species - Homo sapiens, Macaca mulatta, Arabidopsis thaliana and Drosophila melanogaster, demonstrating its high applicability. As an example, we use improved mutation rate estimates to stratify human genes into distinct groups which are enriched for different functions, and highlight that many developmental genes are subject to high mutational burden. The open-source software and generated mutation rate maps can greatly facilitate related research.
MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses
Authors: Martos-Folgado Inmaculada , Lorenzo Cristina , Busse Christian E. , Delgado Pilar , Mur Sonia , Cobos Laura , Martín-Ventura Jose Luis , Escolà-Gil Joan Carles , Wardemann Hedda , Ramiro Almudena R 
Published: October 2021

ABSTRACTAtherosclerosis is a chronic inflammatory disease of the arteries that can lead to thrombosis, infarction and stroke and is the leading cause of mortality worldwide. Immunization of pro-atherogenic mice with malondialdehyde-modified low-density lipoprotein (MDA-LDL) neo-antigen is athero-protective. However, the immune response to MDA-LDL and the mechanisms responsible for this athero-protection are not completely understood. Here, we find that immunization of mice with MDA-LDL elicits memory B cells, plasma cells, and switched anti-MDA-LDL antibodies as well as clonal expansion and affinity maturation, indicating that MDA-LDL triggers a bona fide germinal center antibody response. Further, Prdm1fl/flAicda-Cre+/kiLdlr-/- pro-atherogenic chimeras, which lack germinal center-derived plasma cells, show accelerated atherosclerosis. Finally, we show that MDA-LDL immunization is not athero-protective in mice lacking germinal-center derived plasma cells. Our findings give further support to the development of MDA-LDL-based vaccines for the prevention or treatment of atherosclerosis.
Development of amyloid beta gold nanorod aggregates as optoacoustic probes
Authors: Soliman Mahmoud G , Davies Hannah A , Sharkey Jack , Lévy Raphaël , Madine Jillian 
Published: October 2021

AbstractPropagation of small amyloid beta (Aβ) aggregates (or seeds) has been suggested as a potential mechanism of Alzheimer’s disease progression. Monitoring the propagation of Aβ seeds in an organism would enable testing of this hypothesis and, if confirmed, provide mechanistic insights. This requires a contrast agent for long-term tracking of the seeds. Gold nanorods combine several attractive features for this challenging task, in particular, their strong absorbance in the infrared (enabling optoacoustic imaging) and the availability of several established protocols for surface functionalization. In this work, polymer-coated gold nanorods were conjugated with anti-Aβ antibodies and specifically attached to pre-formed Aβ seeds. The resulting complexes were characterized for their optical properties by UV/Vis spectroscopy and multispectral optoacoustic tomography. The complexes retained their biophysical properties, i.e. their ability to seed Aβ fibril formation. They remained stable in biological media for at least 2 days and showed no toxicity to SH-SY5Y neuroblastoma cells up to 1.5 nM and 6 μM of gold nanorods and Aβ seeds, respectively. Taken together, this study describes the first steps in the development of probes for monitoring the spread of Aβ seeds in animal models.
Impact of Grain for Green Project on Water Resources and Ecological Water Stress in Yanhe River Basin
Authors: Han Yuping , Xia Fan , Huang Huiping , Mu Wenbin 
Published: October 2021

AbstractGrain for Green project (GGP) initialed by China government since 1999 has achieved substantial achievements accompanied with surface runoff decrease in the Loess Plateau but impacts of large-scale afforestation on regional water resources are uncertain. Hence, the objective of this study is to explore the impact of land use change on generalized water resources and ecological water stress using blue and green water concept taking Yanhe River Basin as a case study. Soil and Water Assessment Tool (SWAT) is applied to quantify summary of green and blue water which is defined as generalized water resources, ecological water requirement of vegetation (forest and grass), agricultural water footprint and virtual water flow are considered as regional water requirements. Land use types of 1980 (scenario I), 2017 (scenario II) are input in SWAT model while keeps other parameters constant in order to isolate the influence of land use changes. Results show that average annual difference of blue, green and generalized water resources is −72.08 million m3, 24.34 million m3, −47.74 million m3respectively when simulation results of scenario II subtracts scenario I and it presents that land use change caused by GGP leads to decrease in blue and generalized water resources whereas increase in green water resources. SURQ in scenario I is more than that in scenario IIin all the study period from 1980-2017, green water storage in scenario I is more than that in scenario II in all the study period except in 1998; whereas LATQ in scenario I is less than that in scenario II except in 2000 and 2015, GWQ in 1992, 2000 and 2015, green water flow in 1998. Blue water, green water storage and green water flow in scenario II is less than that in scenario I in the whole basin, 12.89 percent of the basin and 99.21 percent of the basin respectively. Total WF increases from 1995 to 2010 because forest WF increases significantly in this period though agricultural WF and grass WF decreases. Ecological water stress index has no obvious temporal change trend in both land use scenarios but ecological water stress index in scenario II is more than that in scenario I which illustrates that GGP leads to increase of ecological water stress from perspective of generalized water resources
Effects of electroacupuncture on the expression of hypothalamic neuropeptide Y and ghrelin in pubertal rats with polycystic ovary syndrome
Authors: Li Yang , Zhi Wang , Haoxu Dong , Qing Wang , Ling Cheng , Ping Yi , Dongmei Huang 
Published: October 2021

AbstractBackgroundPolycystic ovary syndrome often starts in puberty, and its pathogenesis is not clear. This study aimed to explore the pathogenesis of pubertal polycystic ovary syndrome (PCOS) and assess the therapeutic effect of electroacupuncture on pubertal PCOS.MethodsDihydrotestosterone (DHT) was used to induce rat models of pubertal PCOS. pubertal rats with PCOS were randomly divided into a model group (M), an electroacupuncture group (EA), and a sham acupuncture group (SA). Age-matched normal rats were regarded as normal controls (N). Rats were treated with EA or SA five times a week for 25 minutes during their 6th–7th week. At the end of the experiment, we observed any changes in ovarian morphology; detected levels of metabolic indices in serum, the hypothalamus and pancreas.ResultsEA significantly improved estrous cycle disorders and the ovarian polycystic morphology in pubertal rats with PCOS, but SA only improved disorders of the estrous cycle. The serum levels of insulin, neuropeptide Y(NPY) and fasting blood glucose(FBG) increased significantly, while the serum levels of ghrelin(GHRL) decreased in the model group. After treatment with EA, the levels of NPY and FBG went into decrease, whereas the levels of GHRL and insulin increased. There was few differences in the hypothalamic expression of galanin (GAL), galanin-like peptide (GALP) and ghrelin receptor(GHSR) between the four groups. The upregulation of NPY mRNA and neuropeptide Y2 receptor(NPY2R) mRNA and the downregulation of GHRL protein and mRNA in the hypothalamus, and the increased expression of NPY and NPY2R as well as the decreased expression of GHRL in the arcuate nucleus (ARC) can be rescued by EA. But, surprisingly, SA seem to make no difference to the levels of FBG and insulin, and the protein expression of ghrelin in the hypothalamus and ARC. Co-expression of kisspeptin and GHSR, and co-expression of gonadotrophin releasing hormone(GnRH) and NPY2R were observed in ARC. No differences were found between groups in protein of GAL, GALP and GHRL expression in the pancreas. Neither EA nor SA can attenuate the upregulated kisspeptin protein expression in the pancreas of PCOS model rats.ConclusionsEA and SA improved the symptoms of pubertal PCOS rats, and the mechanism might be associated with regulating hypothalamic NPY and ghrelin levels.
Estimated quantity of swine virus genomes based on quantitative PCR analysis in spray-dried porcine plasma samples collected from multiple manufacturing plants
Authors: Blázquez Elena , Pujols Joan , Segalés Joaquim , Rodríguez Carmen , Campbell Joy , Russell Louis , Polo Javier 
Published: October 2021

AbstractThis survey was conducted to estimate the incidence and level of potential viral contamination in commercially collected porcine plasma. Samples of spray dried porcine plasma (SDPP) were collected over a 12-month period from eight spray drying facilities in Spain, England, Northern Ireland, Brazil, Canada, and the United States. In this survey, viral load for several porcine pathogens including SVA, TGEV, PRRSV (EU and US strains), PEDV, PCV2, SIV, SDCoV and PPV were determined by qPCR. Regression of Ct on TCID50 of serial diluted stock solution of each virus allowed the estimate of potential viral level in SDPP and unprocessed liquid plasma (using typical solids content of commercially collected porcine plasma). In this survey SVA, TGEV or SDCoV were not detected in any of the SDPP samples. Brazil SDPP samples were free of PRRSV and PEDV. Samples of SDPP from North America primarily contained the PRRSV-US strain while the European samples contained the PRRSV-EU strain (except for one sample from each region containing a low estimated level of the alternative PRRSV strain). Estimated viral level tended to be low ranging from <1.0 log10TCID50to <2.5 log10TCID50. Estimated level of SIV was the exception with a very low incidence rate but higher estimated viral load <3.9 log10TCID50. In summary, the incidence of potential viral contamination in commercially collected porcine plasma was variable and estimated virus level in samples containing viral DNA/RNA was low.
MiR-30a-5p alters epidermal terminal differentiation during aging by regulating BNIP3L/NIX-dependent mitophagy
Authors: Chevalier Fabien P , Rorteau Julie , Ferraro Sandra , Martin Lisa S , Gonzalez-Torres Alejandro , Berthier Aurore , El Kholti Naima , Lamartine Jérôme 
Published: October 2021

AbstractChronological aging is characterized by an alteration of the genes regulatory network. In human skin, epidermal keratinocytes fail to differentiate properly with aging, leading to the weakening of the epidermal function. MiR-30a is particularly overexpressed with epidermal aging, but the downstream molecular mechanisms are still uncovered. The aim of this study was to decipher the effects of miR-30a overexpression in the human epidermis, with a focus on keratinocyte differentiation. We formally identified the mitophagy receptor BNIP3L as a direct target of miR-30a. Using a 3D organotypic model of reconstructed human epidermis overexpressing miR-30a, we observed a strong reduction of BNIP3L expression in the granular layer. In human epidermal sections of skin biopsies from donors of different ages, we observed a similar pattern of BNIP3L decrease with aging. Moreover, human primary keratinocytes undergoing differentiationin vitroalso showed a decreased expression ofBNIP3Lwith age, together with a retention of mitochondria. Moreover, aging is associated with altered mitochondrial metabolism in primary keratinocytes, including decreased ATP-linked respiration. Thus, miR-30a is a negative regulator of programmed mitophagy during keratinocytes terminal differentiation, impairing epidermal homeostasis with aging.
P300 Parameters Over the Lifespan: Validating Target Ranges from an In-Clinic Platform
Authors: Oakley D. S. , Fosse K. , Gerwick E. , Joffe D. , Oakley D. A. , Prather A. , Lucini F Arese , Palermo F. X. 
Published: October 2021

AbstractBackgroundEvoked potential (ERP) markers extracted from an EEG exam can provide novel sources of information regarding brain function allowing changes in cognition, from conditions such as concussion or unhealthy aging, to be measured and tracked over time. Age-related targets can provide useful guides for practitioners, trainers, and patients seeking to optimize and track brain function over time.Objective 1: To compare age-related changes in auditory P300 metrics of latencies and amplitudes collected in the course of routine clinical evaluations with published trends from research.Objective 2: To establish within-person test-retest variances for these P300 metrics.Objective 3: To validate a method for presenting age-stratified target ranges of P300 metrics.ParticipantsOne thousand seven-hundred and seventy-eight reference subjects aged 13-90.MethodsAudio P300 was measured as part of a health screening exam for studies through Colorado University, Children’s Hospital Colorado, Boone Heart Institute, WAVi Co., and various clinics alongside other clinical evaluations.ResultsThe age-related trends in both the P300 latency and amplitude measured in clinic match the age-related trends from previous research. In particular, the 2 control group endpoints at 20 and 90 years match the linear slopes predicted for age-related decline from early studies, and the inclusion of all ages produces a maturation prediction of a recent meta analysis where metrics peak near 20 years of age. Large between-person variances are observed across all studies but within-person variances remain consistent with previous studies.ConclusionIn-clinic measures of P300 latency and amplitude corroborate the age-related trends of published research taken over the last several decades. Large between-person variance remains, leaving P300 best suited for within-person comparison.
The regenerative response of cardiac interstitial cells
Authors: Rolland Laura , Harrington Alenca , Faucherre Adèle , Gangatharan Girisaran , Gamba Laurent , Severac Dany , Pratlong Marine , Moore-Morris Thomas , Jopling Chris 
Published: October 2021

AbstractUnderstanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction. Currently, it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration. To understand how interstitial cells behave during cardiac regeneration, we performed single-cell RNA sequencing (scRNA-seq) of regenerating zebrafish hearts. Using a combination of immunohistochemistry, chemical inhibition and novel transgenic animals, we were able to investigate the role of cell type specific responses during cardiac regeneration. This approach allowed us to identify a number of important regenerative mechanisms within the interstitial cell populations. Here, we provide here a detailed insight into how interstitial cells behave during cardiac regeneration and identify a number of novel features of these cells which will serve to increase our understanding of how this process could eventually be induced in humans.
Quantifying the effect of caloric and non-caloric sweeteners in the brain response using EEG and convolutional neural network
Authors: von Atzingen Gustavo Voltani , Miñano Hubert Luzdemio Arteaga , da Silva Amanda Rodrigues , Ortega Nathalia Fontanari , Costa Ernane José Xavier , de Sousa Silva Ana Carolina 
Published: October 2021

AbstractSweetener type can influence sensory properties and consumer’s acceptance and preference for low-calorie products. An ideal sweetener does not exist, and each sweetener must be used in situations to which it is best suited. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. Despite the interest in artificial sweeteners, little is known about how artificial sweeteners are processed in the human brain. Here, we evaluated brain signals of 11 healthy subjects when they tasted passion fruit juice equivalently sweetened with sucrose (9.4 g/100 g), sucralose (0.01593 g/100 g), or aspartame (0.05477 g/100 g). Electroencephalograms were recorded for two sites in the gustatory cortex (i.e., C3 and C4). Data with artifacts were disregarded, and the artifact-free data were used to feed a CNN. Our results indicated that the brain responses distinguish juice sweetened with different sweeteners with an average accuracy of 0.823.Practical ApplicationsFinding sweeteners that best fit consumer preferences evolves understanding how the gustatory cortex processes sweeteners. Ideal equivalence will occur when the brain is no longer able to distinguish stimuli that are consciously perceived. This study presents a method of signal acquisition using a single channel and an open-source processing environment. This would allow, for example, to disregard the use of a commercial electroencephalograph and expand the studies in this area and offering to food industry additional tools in the development of products sweetened with non-caloric sweeteners.