bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escaping through the predator’s gill cleft: A defensive tactic of juvenile eels after capture by predatory fish
Authors: Hasegawa Yuha , Yokouchi Kazuki , Kawabata Yuuki 
Published: June 2021

SummarySome prey animals can actively escape from predators even after being captured, but knowledge of such behaviors is still limited, especially in vertebrates. Here, we report the unique active escape behavior of Japanese eel Anguilla japonica juveniles through the gill cleft of the predatory fish Odontobutis obscura. Of the 54 A. japonica juveniles captured by the predator, 28 escaped via the predator’s gill, and most escaped individuals survived afterwards. In all escaped individuals, their tails emerged first from the gill cleft of the predator, and then their whole bodies slipped out in a backward direction from the cleft. These findings indicate that A. japonica juveniles have the specialized antipredator tactic, which provides the basis for further investigation from behavioral, ecological, and evolutionary perspectives.
Identification of the CoA-ester intermediates and genes involved in the cleavage and degradation of the steroidal C-ring by Comamonas testosteroni TA441
Authors: Horinouchi Masae , Hayashi Toshiaki 
Published: June 2021

ABSTRACTComamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, β-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage process. Here, we elucidated the C-ring cleavage and the β-oxidation cycle that follows. ScdL1L2, a 3-ketoacid Coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα-H-4α [3′-propionic acid]-7aβ-methylhexahydro-1,5-indanedione; HIP)-CoA ester in the previous study; however, this study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves C ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21 and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then a water molecule is added by ScdN for further degradation by β-oxidation. ScdN is considered to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR.IMPORTANCEStudies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain materials for steroid drugs. Steroid-degrading bacteria are globally distributed, and the role of bacterial steroid degradation in the environment as well as in human is attracting attention. The overall degradation of steroidal four rings is proposed, however there are still much to be revealed to understand the complete degradation pathway. This study aims to uncover the whole steroid degradation process in C. testosteroni, which is one of the most studied representative steroid degrading bacteria and is suitable for exploring the degradation pathway because the involvement of degradation-related genes can be determined by gene disruption.
Single Cell Raman-Deuterium Isotope Probing for Drug Resistance of Elizabethkingia spp
Authors: Yuan Shuying , Chen Yanwen , Song Yizhi , Zou Lin , Lin Kaicheng , Lu Xinrong , Liu Ruijie , Zhang Shaoxing , Shen Danfeng , Song Zhenju , Tong Chaoyang , Chen Li , Sun Guiqin 
Published: June 2021

AbstractNosocomial infection associated with Elizabethkingia spp. is an emerging clinical concern characterized by multi-drug resistance and severe clinical consequences particularly in immunocompromised individuals and infants. Efficient control of this infection demands quick and reliable methods to determine the right drugs for the treatment. In this study, E. meningoseptica ATCC 13253 and four clinical isolates of Elizabethkingia spp. obtained from China, were subjected to single cell Raman spectroscopy analysis coupling with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could generate an antimicrobial susceptibility testing result for Elizabethkingia spp. colonies within 4 hours based on their metabolisms variations at single cell level, and the drug resistant spectra of Elizabethkingia spp. determined by single cell Raman-DIP were consistent with the classical MIC method. Meanwhile single cell Raman spectroscopy (single cell RS) was applied to analyze Raman spectra of Elizabethkingia spp., which were revealed that their ratios of nucleic acid/protein were lower than other gram-negative pathogens and isolates from different origins could be distinguished by their Raman fingerprint. The in vitro results confirmed that minocycline and levofloxacin are first-line antimicrobials for Elizabethkingia spp. infection.
Single-cell RNA sequencing uncovers the excitatory/inhibitory synaptic unbalance in the retrosplenial cortex after peripheral nerve injury
Authors: Wang Jing-Hua , Wu Cheng , Lian Yan-Na , Wang Zi-Yue , Dong Jia-jun , Wu Qin , Liu Li , Sun Li , Chen Wei , Chen Wenjuan , Zhang Zhi , Zhuo Min , LI Xiang-Yao 
Published: June 2021

AbstractNerve injury in the somatosensory pathway may induce maladaptive changes at the transcriptional or protein level, contributing to the development and maintenance of neuropathic pain. In contrast to the retrosplenial cortex (RSC), which processes nociceptive information and exhibits structural and molecular changes after nerve injury, detailed transcriptional changes in the RSC are not yet known. Here we confirm the involvement of the RSC in regulating pain sensation and observe that the same peripheral stimulation activates more retrosplenial neurons after nerve injury; reducing the activities of CaMKIIα+ splenial cells relieves peripheral pain hypersensitivity after nerve injury. Using a single-cell RNA sequencing (scRNA-seq) approach, we identified cell-type-specific gene expression changes after nerve injury, and the gene set enrichment analysis results revealed suppressed ion homeostasis in CaMKIIα+ neurons. Furthermore, examination of the expression of genes encoding ligand-gated ion channels showed a decrease in Gabar1a but an increase in Gria1 in CaMKIIα+ neurons; consistently, we confirmed the unbalanced excitatory/inhibitory synaptic transmission by using the electrophysiological recording approach. Moreover, micro-infusion of 1-Naphthyl acetyl spermine in the RSC to reduce excitatory synaptic transmission alleviated peripheral pain hypersensitivity. Our data confirm the involvement of the RSC in pain regulation and provide information on cell type-dependent transcriptomic changes after nerve injury, which will contribute to the understanding of the mechanisms mediating neuropathic pain.
Comprehensive profiling of liver x receptor splicing in triple negative breast cancer reveals existence of novel splice variants that are prognostic for survival
Authors: Lianto Priscilia , Moore J. Bernadette , Hughes Thomas A. , Thorne James L. 
Published: June 2021

AbstractThe liver x receptors (LXR) alpha and beta are ligand-responsive transcription factors that link homeostatic control of lipid metabolism with cancer pathophysiology and prognosis. LXR activity is elevated in triple negative breast cancer relative to other breast cancer subtypes, driving gene signatures associated with drug resistance and metastasis. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Seven splice variants of LXRα or LXRβ were detected. Three have not been recorded previously and five were prognostic. High expression of full length LXRα was associated with shorter disease-free survival but splice variants harbouring truncations of the ligand binding domain were prognostic for improved survival. All LXRβ variants were associated with longer disease-free survival. Mechanistically, while full length LXRα positively correlated with target gene expression in primary samples, LXRβ was inversely correlated. We conclude that canonical LXRα function is an oncogenic driver of triple negative tumour pathophysiology that can be countered by high expression of truncated splice variants and/or full length LXRβ.HighlightsExpression of full length LXRα is associated with shorter disease-free survival of triple negative breast cancer patientsA systematic evaluation of cell lines and primary tumour samples indicates LXR splicing is extensive in breast cancerConfirmation of three new LXR splice variants at transcript and protein levelExpression of full length LXRβ or LXRα splice variants that harbour truncated ligand binding domains are associated with better prognosisExpression of LXR target genes is positively correlated with LXRα in relapsed patients and inversely correlated with LXRβ in survivors.
Placental polyamines regulate acetyl-coA and histone acetylation in a sex-specific manner
Authors: Aye Irving LMH , Gong Sungsam , Avellino Giulia , Barbagallo Roberta , Gaccioli Francesca , Jenkins Benjamin J , Koulman Albert , Murray Andrew J , Charnock-Jones D Stephen , Smith Gordon CS 
Published: June 2021

AbstractFetal sex differences play an important role in the pathophysiology of several placenta-related pregnancy complications. We previously reported that the maternal circulating level of a polyamine metabolite was altered in a fetal sex-specific manner, and was associated with pre-eclampsia and fetal growth restriction. Here we show that placental polyamine metabolism is altered in these disorders and that polyamines influence widespread changes in gene expression by regulating the availability of acetyl-CoA which is necessary for histone acetylation. Sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding the enzyme spermine synthase in female placentas, as evidenced by biallelic expression of the gene in female trophoblasts. Polyamine depletion in primary human trophoblasts impairs glycolysis and mitochondrial metabolism resulting in decreased availability of acetyl-CoA and global histone hypoacetylation, in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA–sequencing identifies downregulation of progesterone biosynthetic pathways as a key target and polyamine depletion reduced progesterone release in male trophoblasts. Collectively, these findings suggest that polyamines regulate placental endocrine function through metabolic regulation of gene expression, and that sex differences in polyamine metabolism due to XCI escape may buffer the effects of placental dysfunction in pregnancy disorders.
NanoSpring: reference-free lossless compression of nanopore sequencing reads using an approximate assembly approach
Authors: Meng Qingxi , Chandak Shubham , Zhu Yifan , Weissman Tsachy 
Published: June 2021

ABSTRACTThe amount of data produced by genome sequencing experiments has been growing rapidly over the past several years, making compression important for efficient storage, transfer and analysis of the data. In recent years, nanopore sequencing technologies have seen increasing adoption since they are portable, real-time and provide long reads. However, there has been limited progress on compression of nanopore sequencing reads obtained in FASTQ files since most existing tools are either general-purpose or specialized for short read data.We present NanoSpring, a reference-free compressor for nanopore sequencing reads, relying on an approximate assembly approach. We evaluate NanoSpring on a variety of datasets including bacterial, metagenomic, plant, animal, and human whole genome data. For recently basecalled high quality nanopore datasets, NanoSpring, which focuses only on the base sequences in the FASTQ file, uses just 0.35-0.65 bits per base which is 3-6x lower than general purpose compressors like gzip. NanoSpring is competitive in compression ratio and compression resource usage with the state-of-the-art tool CoLoRd while being significantly faster at decompression. NanoSpring is available on GitHub athttps://github.com/qm2/NanoSpring.
Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor
Authors: Wang Yue , Guo Shimeng , Zhuang Youwen , Yun Ying , Xu Peiyu , He Xinheng , Guo Jia , Yin Wanchao , Xu H. Eric , Xie Xin , Jiang Yi 
Published: June 2021

AbstractGhrelin, also called “the hunger hormone”, is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.
Beyond tracking climate: niche shifts during native range expansion and their implications for novel invasions
Authors: Lustenhouwer Nicky , Parker Ingrid M. 
Published: June 2021

AbstractAimAlthough ecological niche models have been instrumental in understanding the widespread species distribution shifts under global change, rapid niche shifts limit model transferability to novel locations or time periods. Niche shifts during range expansion have been studied extensively in invasive species, but may also occur in native populations tracking climate change. We compared niche shifts during both types of range expansion in a Mediterranean annual plant to ask (i) whether the species’ native range expansion tracked climate change, (ii) whether further range expansion was promoted by niche expansion, and (iii) how these results changed forecasts of two ongoing invasions in Australia and California.LocationEurasian Holarctic, California and AustraliaTaxonDittrichia graveolens (L.) Greuter (Asteraceae)MethodsNiche shifts were quantified in both environmental and geographic space, using the framework of niche centroid shift, overlap, unfilling, and expansion (COUE) as well as Maximum Entropy modelling. We used the historic native distribution and climate data (1901-1930) to project the expected distribution in the present climate (1990-2019), and compared it to the observed current distribution of D. graveolens. Finally, we compared invasion forecasts based on the historic and present native niches.ResultsWe found that D. graveolens expanded its native range well beyond what would be sufficient to track climate change, associated with a 5.5% niche expansion towards more temperate climates. In contrast, both invasions showed niche conservatism, and were (still) constrained to climatic areas matching the historic native niche.Main conclusionsour results show that contrary to hypotheses in the literature, niche shifts are not necessarily more rapid in invasions than in native range expansions. We conclude that niche expansion during the process of climate tracking may cause further range expansion than expected based on climate change alone.
Neonicotinoid and pyrethroid combination: A tool to manage insecticide resistance in malaria vectors? Insights from experimental evolution
Authors: Zoh Marius Gonse , Bonneville Jean-Marc , Tutagana Jordan , Laporte Frederic , Fodjo Behi K. , Mouhamadou Chouaibou S. , Sadia Christabel , McBeath Justin , Schmitt Frederic , Horstmann Sebastian , Reynaud Stephane , David Jean-Philippe 
Published: June 2021

AbstractBackgroundThe introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora® Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance ofAn. gambiaeto the separated or combined components of this combination. A field-derivedAn. gambiaeline carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines.ResultsThis study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation while clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with the ones conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was observed on a cytochrome P450 gene cluster previously associated with resistance. Within this cluster, the geneCYP6M1showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure suggested that the selection of variants affecting its active site can enhance clothianidin metabolism.ConclusionsIn the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.
Thermodynamic genome-scale metabolic modeling of metallodrug resistance in colorectal cancer
Authors: Herrmann Helena A. , Rusz Mate , Baier Dina , Jakupec Michael A. , Keppler Bernhard K. , Berger Walter , Koellensperger Gunda , Zanghellini Jürgen 
Published: June 2021

AbstractBackgroundMass spectrometry-based metabolomics approaches provide an immense opportunity to enhance our understanding of the mechanisms that underpin the cellular reprogramming of cancers. Accurate comparative metabolic profiling of heterogeneous conditions, however, is still a challenge.MethodsMeasuring both intracellular and extracellular metabolite concentrations, we constrain four instances of a thermodynamic genome-scale metabolic model of the HCT116 colorectal carcinoma cell line to compare the metabolic flux profiles of cells that are either sensitive or resistant to ruthenium- or platinum-based treatments with BOLD-100/KP1339 and oxaliplatin, respectively.ResultsNormalizing according to growth rate and normalizing resistant cells according to their respective sensitive controls, we are able to dissect metabolic responses specific to the drug and to the resistance states. We find the normalization steps to be crucial in the interpretation of the metabolomics data and show that the metabolic reprogramming in resistant cells is limited to a select number of pathways.ConclusionsHere we elucidate the key importance of normalization steps in the interpretation of metabolomics data, allowing us to uncover drug-specific metabolic reprogramming during acquired metal-drug resistance.
Integrative Epigenomic and High-Throughput Functional Enhancer Profiling Reveals Determinants of Enhancer Heterogeneity in Gastric Cancer
Authors: Sheng Taotao , Ho Shamaine Wei Ting , Ooi Wen Fong , Xu Chang , Xing Manjie , Padmanabhan Nisha , Huang Kie Kyon , Ma Lijia , Ray Mohana , Guo Yu Amanda , Leng Sim Ngak , Anene-Nzelu Chukwuemeka George , Chang Mei Mei , Razavi-Mohseni Milad , Beer Michael A. , Foo Roger Sik Yin , Tan Angie Lay Keng , Ong Xuewen , Skanderup Anders Jacobsen , White Kevin P. , Jha Sudhakar , Tan Patrick 
Published: June 2021

AbstractBackgroundEnhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity – however, most predicted enhancer regions remain to be functionally tested.ResultsAnalyzing 128 epigenomic histone modification profiles of primary GC samples, normal gastric tissues, and GC cell lines, we report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are tumor-associated in vivo (>50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans-acting TFs involved in GC expression. Specifically, we identified cancer-relevant genes (e.g. ING1, ARL4C) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans-acting factor associated with GC enhancer heterogeneity.ConclusionsOur study indicates that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, and provides insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity.