bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictive power of mRNA mapping for Cannabinoid 1 receptor protein in the human brain
Authors: Pak Kyoungjune , Kantonen Tatu , Pekkarinen Laura , Nuutila Pirjo , Nummenmaa Lauri 
Published: March 2022

ABSTRACTType 1 cannabinoid (CB1) receptor is expressed in cortex, hippocampus, amygdala, basal ganglia, and cerebellum. With the help of the Allen Human Brain Atlas, genomic maps visualize not only the gene expression across whole brain regions, but also the functional profile of brain structures. Therefore, it is more timely than ever to integrate genomic mapping from brain mRNA atlas with the protein expression from positron emission tomography (PET) scans for better understanding of CB1 receptor of the human brain. F18-FMPEP-d2 PET scans were retrieved from the AIVO neuroinformatics project. Autoradiography data were based on the study with H3-CP55940. mRNA expressions of CNR1 gene (Cannabinoid receptor 1) were downloaded from the Allen Human Brain Atlas. Volume of distribution (VT) from F18-FMPEP-d2 PET scans, CNR1 gene expression, and H3-CP55940 binding were calculated and Spearman correlation analysis was performed. Also, a meta-analysis was done to investigate the association between protein expression from PET and mRNA expression from the Allen Human Brain Atlas. Between VT of F18-FMPEP-d2 PET scans and CNR1 mRNA expression, moderate strength of correlation was observed (rho = 0.5026, p = 0.0354). Strong positive correlation was also found between CNR1 mRNA expression and H3-CP55940 binding (rho = 0.6727, p = 0.0281), validating the finding between F18-FMPEP-d2 PET scans and CNR1 mRNA. From the meta-analysis, the correlation coefficient ranged from −0.46 to 0.99, with a pooled effect of 0.58. In conclusion, the moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression. From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains.HIGHLIGHTSWe investigated the association between CNR1 gene expression from the Allen Human Brain Atlas and type 1 cannabinoid (CB1) receptor expression from F18-FMPEP-d2 PET scans.The moderate to strong associations between gene and protein expression for CB1 receptor in the human brain were observed that CNR1 mRNA mapping might have the predictive power for in vivo CB1 receptor protein expression.From the meta-analysis, the moderate to strong correlation was observed between mRNA expression and protein expressions across multiple genes, showing the predictive power of genes to estimate protein levels of human brains.
Exploring the Neoantigen burden in Breast Carcinoma Patients
Authors: Animesh Sambhavi , Ren Xi , An Omer , Chen Kaijing , Lee Soo Chin , Yang Henry , Fullwood Melissa J 
Published: March 2022

AbstractIn this study we performed a multi-omics analysis comprising whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) on seven breast cancer patients, consisting of three Estrogen receptor (ER) positive and four Triple negative breast cancer (TNBC) subtypes to understand the neoantigen burden in breast cancer tumor samples. We predicted both class-I and class-II human leukocyte antigen (HLA) bound neoantigens by analyzing matched tumor-normal pair of exomes. Across all the patients, we predicted 434 unique neoantigens (NeoFil) in total, affecting 237 different genes and 87% of them (n = 378) are expressed at RNA level (Neoexp). The missense mutations (87%) are the major contributor in neoantigen (Neoexp) generation, followed by frameshift (11%) and indels (2%). The neoantigens (NeoFil) were found to be positively correlated with the somatic mutations (R2 = 0.89). We also noted that the vast majority (99.98%) of the predicted neoantigens are patient specific. Overall, the current study offers significant insight into the neoantigen profile in tumor types with intermediate/low mutation burdens like breast cancer.
Compositionally Constrained Sites Drive Long Branch Attraction
Authors: Szánthó Lénárd L. , Lartillot Nicolas , Szöllősi Gergely J. , Schrempf Dominik 
Published: March 2022

AbstractAccurate phylogenies are fundamental to our understanding of the pattern and process of evolution. Yet, phylogenies at deep evolutionary timescales, with correspondingly long branches, have been fraught with controversy resulting from conflicting estimates from models with varying complexity and goodness of fit. Analyses of historical as well as current empirical datasets, such as alignments including Microsporidia, Nematoda or Platyhelminthes, have demonstrated that inadequate modeling of across-site compositional heterogeneity, which is the result of biochemical constraints that lead to varying patterns of accepted amino acids along sequences, can lead to erroneous topologies that are strongly supported. Unfortunately, models that adequately account for across-site compositional heterogeneity remain computationally challenging or intractable for an increasing fraction of contemporary datasets. Here, we introduce “compositional constraint analysis”, a method to investigate the effect of site-specific constraints on amino acid composition on phylogenetic inference. We show that more constrained sites with lower diversity and less constrained sites with higher diversity exhibit ostensibly conflicting signal under models ignoring across-site compositional heterogeneity that lead to long branch attraction artifacts and demonstrate that more complex models accounting for across-site compositional heterogeneity can ameliorate this bias. We present CAT-PMSF, a pipeline for diagnosing and resolving phylogenetic bias resulting from inadequate modeling of across-site compositional heterogeneity based on the CAT model. CAT-PMSF is robust against long branch attraction in all alignments we have examined. We suggest using CAT-PMSF when convergence of the CAT model cannot be assured. We find evidence that compositionally constrained sites are driving long branch attraction in two metazoan datasets and recover evidence for Porifera as the sister group to all other animals.
Assessment of binocular fixational eye movements including cyclotorsion with split-field binocular scanning laser ophthalmoscopy
Authors: Hofmann Julia , Domdei Lennart , Jainta Stephanie , Harmening Wolf 
Published: March 2022

AbstractFixational eye movements are a hallmark of human gaze behavior, yet little is known about how they interact between fellow eyes. Here, we designed, built and validated a split-field binocular scanning laser ophthalmoscope (bSLO) to record high-resolution eye motion traces from both eyes of six observers during fixation at different binocular vergence conditions. In addition to microsaccades and drift, torsional eye motion could be extracted, with a spatial measurement error of less than 1 arcmin. Microsaccades were strongly coupled between fellow eyes under all conditions. No monocular microsaccade occurred and no significant delay between microsaccade onsets across fellow eyes could be detected. Cyclotorsion was also firmly coupled between both eyes, occurring typically in conjugacy, with gradual changes during drift and abrupt changes during saccades.
Synchronic resisto-genesis effects identify most prevalent mechanism in Acinetobacter baumannii
Authors: Alaei Najmeh , Bahador Abbas , Alaei Azadeh 
Published: March 2022

AbstractAcinetobacter baumannii as deadliest infection agent to ICU patients challenge experimental treatment in lack of new antibiotic and non-optimal recommendations. Despite confirm importance of infectious ICU sources, IC2 strains, ISAba/blaOXA genes and colistin in adequate concentrations or combination therapy due to potential heteroresistance; this study reveals unusual hypersensitive colistin- and sensitive aminoglycosides-resistant strains using designed methods, antibio-dendrogram classification and a computational table. Accordingly, lipopolysaccharide loss-mediated penetration and upregulated AdeAB pump-mediated compounds exclusion, are found to be causes of these abnormalities. Consequently, these simultaneous resistances termed synchronic resisto-genesis effects, drive population and create abnormal multidrug-resistant strains; while, delay extensively drug-resistant phenotype. This phenomenon predicts the predominant determinant mechanisms and makes abnormal behavior comprehensible among antibiotic-phenotypic levels or in vitro and vivo observations. Therefore, this method provides preclinical information to address therapeutic resistance in future microbial or cancer cell studies, and improves drug choosing in combination therapies, like use of inhibitory drugs.
GABAergic modulation of conflict adaptation and response inhibition
Authors: Aponte Eduardo A. , Faßbender Kaja , Heinzle Jakob , Ettinger Ulrich 
Published: March 2022

AbstractAdaptive behavior is only possible by stopping stereotypical actions to generate new plans according to internal goals. It is response inhibition —the ability to stop actions automatically triggered by exogenous cues— that allows for the flexible interplay between bottom-up, stimulus driven behaviors, and top-down strategies. In addition to response inhibition, cognitive control draws on conflict adaptation, the facilitation of top-down actions following high conflict situations. It is currently unclear whether and how response inhibition and conflict adaptation depend on GABAergic signaling, the main inhibitory neurotransmitter in the human brain. Here, we applied a recently developed computational model (SERIA) to data from two studies (N=150 & 50) of healthy volunteers performing Simon and antisaccade tasks. One of these datasets was acquired under placebo-controlled pharmacological enhancement of GABAergic transmission (lorazepam, an allosteric modulator of the GABA-A receptor). Our model-based results suggest that enhanced GABA-A signaling boosts conflict adaptation but impairs response inhibition. More generally, our computational approach establishes a unified account of response inhibition and conflict adaptation in the Simon and antisaccade tasks and provides a novel tool for quantifying specific aspects of cognitive control and their modulation by pharmacology or disease.Author SummaryOur capacity to prepare for situations that afford conflicting responses (conflict adaptation) and to stop our immediate impulses in these scenarios (response inhibition) are the hallmark of cognitive control. As these abilities require both the stopping or slowing of response tendencies, a natural question is whether they are mediated by inhibitory neurotransmission in the brain. Here, we combined computational modeling with two experiments to investigate how conflict adaptation and response inhibition interact with each other (experiment 1) and how these are modulated by lorazepam (experiment 2), a positive modulator of the GABA-A receptor, one of the main inhibitory receptors in the human brain. Using our computational model to disentangle conflict adaptation and response inhibition, our results indicate that while lorazepam impaired response inhibition, it improved conflict adaptation. Thus, our results suggests that conflict adaptation is mediated by GABA-A neurotransmission.
An Arrayed Genome-Wide Perturbation Screen Identifies the Ribonucleoprotein hnRNP K As Rate-Limiting for Prion Propagation
Authors: Avar Merve , Heinzer Daniel , Thackray Alana M. , Liu Yingjun , Hruska-Plochan Marian , Sellitto Stefano , Schaper Elke , Pease Daniel P. , Yin Jiang-An , Lakkaraju Asvin K.K. , Emmenegger Marc , Losa Marco , Chincisan Andra , Hornemann Simone , Polymenidou Magdalini , Bujdoso Raymond , Aguzzi Adriano 
Published: March 2022

AbstractA defining characteristic of mammalian prions is their capacity for self-sustained propagation. Theoretical considerations and experimental evidence suggest that prion propagation is modulated by cell-autonomous and non-autonomous modifiers. Using a novel quantitative phospholipase protection assay (QUIPPER) for high-throughput prion measurements, we performed an arrayed genome-wide RNA interference (RNAi) screen aimed at detecting modifiers of prion propagation. We exposed prion-infected cells in high-density microplates to 35’364 ternary pools of 52’746 siRNAs targeting 17’582 genes representing the mouse protein-coding transcriptome. We identified 1191 modulators of prion propagation. While 1151 of these modified the expression of both the pathological prion protein, PrPSc, and its cellular counterpart PrPC, 40 genes affected selectively PrPSc. Of the latter, 20 genes augmented prion production when suppressed. A prominent limiter of prion propagation was the heterogeneous nuclear ribonucleoprotein Hnrnpk. Psammaplysene A (PSA), which binds Hnrnpk, reduced prion levels in cultured cells and protected them from cytotoxicity. PSA also reduced prion levels in infected cerebellar organotypic slices and alleviated locomotor deficits in prion-infected Drosophila melanogaster expressing ovine PrPC. Hence, genome-wide QUIPPER-based perturbations can discover actionable cellular pathways involved in prion propagation. Finally, the unexpected identification of a prioncontrolling ribonucleoprotein suggests a role for RNA in the generation of infectious prions.
Koisio Technology-Modulated Cell Culture Media can Significantly Increase the Antioxidant Capacity of Mouse Fibroblasts
Authors: Zhang Mingchao , Men Yinghui , Zhu Qi , Ying Weihai 
Published: March 2022

AbstractOxidative stress is not only a critical common pathological factor of numerous diseases, but also an important factor in the aging process. It is highly valuable to discover novel and economic substances for enhancing the antioxidant capacity of human body. In this study we used a cell culture model to determine the antioxidant capacity of Koisio technology-modulated solutions without additions of any external substances. Our study has obtained the following findings: First, the cells cultured in Koisio technology-modulated cell culture media (KM) showed significantly greater capacity to decrease H2O2-induced oxidative stress, compared with the cells cultured in regular cell culture media; second, the cells cultured in KM showed significantly greater capacity to resist H2O2-induced decreases in cell number, compared with the cells cultured in regular cell culture media; and third, the H2O2 prepared in Koisio technology-modulated MEM produced significantly lower levels of decreases in cell number, compared with the H2O2 prepared in MEM. Collectively, our study has indicated that Koisio technology can increase the antioxidant capacity of both solutions and cells without additions of any external substances. Based on our previous findings, we proposed that Koisio technology-modulated solutions increase cellular antioxidant capacity at least partially by increasing intracellular ATP levels.
Soluble signal inhibitory receptor on leukocytes-1 is released from activated neutrophils by proteinase 3 cleavage
Authors: von Richthofen Helen J. , Westerlaken Geertje H.A. , Gollnast Doron , Besteman Sjanna , Delemarre Eveline M. , Rodenburg Karlijn , Moerer Petra , Stapels Daphne A.C. , Andiappan Anand K. , Rötzschke Olaf , Nierkens Stefan , Leavis Helen L. , Bont Louis J. , Rooijakkers Suzan H.M. , Meyaard Linde 
Published: March 2022

ABSTRACTSignal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human granulocytes and monocytes which dampens antimicrobial functions. We previously showed that sputum neutrophils from infants with severe respiratory syncytial virus (RSV) bronchiolitis have decreased SIRL-1 surface expression compared to blood neutrophils, and that SIRL-1 surface expression is rapidly lost fromin vitroactivated neutrophils. This led us to hypothesize that activated neutrophils lose SIRL-1 by ectodomain shedding. Here, we developed an ELISA and measured the concentration of soluble SIRL-1 (sSIRL-1) in RSV bronchiolitis and hospitalized COVID-19 patients, which are both characterized by neutrophilic inflammation. In line with our hypothesis, sSIRL-1 concentration was increased in sputum compared to plasma of RSV bronchiolitis patients, and in serum of hospitalized COVID-19 patients compared to control serum. In addition, we show thatin vitroactivated neutrophils release sSIRL-1 by proteolytic cleavage, which can be prevented by proteinase 3 inhibition. Finally, we found that SIRL-1 shedding is prevented by extracellular adherence protein (Eap) fromS. aureus. Notably, we recently showed that SIRL-1 is activated by PSMα3 fromS. aureus, suggesting thatS. aureusmay counteract SIRL-1 shedding to benefit from preserved inhibitory function of SIRL-1. In conclusion, we are the first to report that SIRL-1 is released from activated neutrophils by proteinase 3 cleavage and that endogenous sSIRL-1 protein is presentin vivo.
Microbial invasion of a toxic medium is facilitated by a resident community but inhibited as the community co-evolves
Authors: Piccardi Philippe , Alberti Géraldine , Alexander Jake M. , Mitri Sara 
Published: March 2022

AbstractPredicting whether microbial invaders will colonize an environment is critical for managing natural and engineered ecosystems, and controlling infectious disease. Invaders often face competition by resident microbes. But how invasions play out in communities dominated by facilitative interactions is less clear. We previously showed that growth medium toxicity can promote facilitation between four bacterial species, as species that cannot grow alone rely on others to survive. Following the same logic, here we allowed other bacterial species to invade the four-species community, and found that invaders could more easily colonize a toxic medium when the community was present. In a more benign environment instead, invasive species that could survive alone colonized more successfully when the residents were absent. Next, we asked whether early colonists could exclude future ones through a priority effect, by inoculating the invaders into the resident community only after its members had co-evolved for 44 weeks. Compared to the ancestral community, the co-evolved resident community was more competitive toward invaders, and less affected by them. Our experiments show how communities may assemble by facilitating one another in harsh, sterile environments, but that arriving after community members have co-evolved can limit invasion success.
Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through Kv7.4 channel upsurge in auditory neurons and hair cells
Authors: Zhang Haiwei , Li Hongchen , Lu Mingshun , Wang Shengnan , Ma Xueya , Wang Fei , Liu Jiaxi , Li Xinyu , Yang Haichao , Zhang Fan , Shen Haitao , Buckley Noel J. , Gamper Nikita , Yamoah Ebenezer N. , Lv Ping 
Published: March 2022

AbstractRepressor element 1-silencing transcription factor (REST) is a transcriptional repressor that recognizes neuron-restrictive silencer elements in the mammalian genomes in a tissue- and cell-specific manner. The identity of REST target genes and molecular details of how REST regulates them are emerging. We performed conditional null deletion of Rest (cKO) in murine hair cells (HCs) and auditory neurons, spiral ganglion neurons (SGNs). Null-deletion of full-length REST resulted in normal HCs and SGNs development but manifested with progressive hearing loss in adulthood. We found that deletion of REST results in an increased abundance of Kv7.4 channels at the transcript, protein, and function levels. Specifically, we found that SGNs and HCs from Rest cKO mice displayed increased Kv7.4 expression and augmented Kv7 currents; SGN’s excitability was also significantly reduced. Administration of Kv7.4 channel activator, fasudil, recapitulated progressive hearing loss in mice.In contrast, inhibition of the Kv7.4 channel by XE991 rescued the auditory phenotype of Rest cKO mice. Previous studies identified some loss-of-function mutations within the Kv7.4-coding gene, Kcnq4, as a causative factor for progressive hearing loss in mice and humans. Thus, the present findings revealed that a critical homeostatic Kv7.4 channel level is required for proper auditory functions.
Exhaustive Cross-linking Search with Protein Feedback
Authors: Zhou Chen , Dai Shuaijian , Lin Yuanqiao , Li Ning , Yu Weichuan 
Published: March 2022

AbstractImproving the sensitivity of protein-protein interaction detection and protein structure probing is a principal challenge in cross-linking mass spectrometry (XL-MS) data analysis. In this paper, we propose an exhaustive cross-linking search method with protein feedback (ECL-PF) for cleavable XL-MS data analysis. ECL-PF adopts an optimizedα/βmass detection scheme and establishes protein-peptide association during the identification of cross-linked peptides. Existing major scoring functions can all benefit from the ECL-PF workflow to a great extent. In comparisons using synthetic datasets and hybrid simulated datasets, ECL-PF achieved three-fold higher sensitivity over standard techniques. In experiments using real datasets, it also identified 91.6% more cross-link spectrum matches and 52.6% more unique cross-links.
A domesticated fungal cultivar recycles its cytoplasmic contents as nutritional rewards for its leafcutter ant farmers
Authors: Leal-Dutra Caio Ambrosio , Yuen Lok Man , Marques Pedro Elias , Guedes Bruno Augusto Maciel , Contreras-Serrano Marta , Shik Jonathan Zvi 
Published: March 2022

ABSTRACTLeafcutter ants farm a fungal cultivar (Leucoagaricus gongylophorus) that converts inedible vegetation into food that sustains colonies with up to millions of workers. Analogous to edible fruits of crops domesticated by humans,L. gongylophorushas evolved specialized nutritional rewards—swollen hyphal cells called gongylidia that package metabolites ingested by ant farmers. Yet, little is known about how gongylidia form, and thus how fungal physiology and ant provisioning interact to farming performance. We explored the mechanisms governing gongylidium formation using microscopy imaging of ant-cultivated fungus and controlledin vitroexperiments with the cultivar grown in isolation from ant farmers. First,L. gongylophorusis polykaryotic (up to 17 haploid nuclei/cell) and our results suggest intracellular nucleus distributions govern gongylidium morphology with their absence in expanding edges arresting apical growth and their presence mediating complex branching patterns. Second, nanoscale imaging (SEM, TEM) shows that the cultivar recycles its own cellular material (e.g. cytosol, mitochondria) through a process called ‘autophagy’ and stores the resulting metabolites in gongylidia. This autophagic pathway is further supported by gongylidium suppression when isolated fungal cultures are grown on media with autophagy inhibitors, and differential transcript expression (RNA-seq) analyses showing upregulation of multiple autophagy genes in gongylidia. We hypothesize that autophagic nutritional reward production istheultimate cultivar service and reflects a higher-level organismality adaptation enabled by strict symmetric lifetime commitment between ant farmers and their fungal crop.