bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstitution of the host holobiont in germ-free rats acutely increases bone growth and affects marrow cellular content
Authors: Czernik PJ , Golonka RM , Chakraborty S , Yeoh BS , Abokor A , Saha P , Yeo JY , Mell B , Cheng X , Baroi S , Joe B , Vijay-Kumar M , Lecka-Czernik B 
Published: July 2020

AbstractIn recent years there has been growing evidence regarding the effect of microbiota on the skeletal growth and homeostasis. Here we present, for the first time, accelerated longitudinal and radial bone growth in young (7-week-old) germ-free male rats after short-term exposure to a newly established gut microbiota. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in tibia diaphysis. In addition, the number of small-in-size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats. The observed changes in bone status were paralleled with a positive shift in microbiota composition towards short chain fatty acids (SCFA)-producing microbes, which reflected a dramatic increase in cecal concentration of SCFA, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels, implicating an involvement of the somatotropic axis. Increased serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase and resembled reversal of dysbiosis in adolescence, which is marked by rapid skeletal expansion. These findings may help in developing microbiota-based therapeutics to combat bone related disorders resulting from hormonal defects and/or malnutrition in children and adolescence.
Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes
Authors: Gainullina Anastasiia , Huang Li-Hao , Todorov Helena , Kim Kiwook , Yng Lim Sheau , Kent Andrew , Jia Baosen , Seddu Kumba , Krchma Karen , Wu Jun , Crozat Karine , Tomasello Elena , Narang Vipin , Dress Regine , See Peter , Scott Charlotte , Gibbings Sophie , Bajpai Geetika , Desai Jigar V. , Maier Barbara , This Sébastien , Wang Peter , Aguilar Stephanie Vargas , Poupel Lucie , Dussaud Sébastien , Zhou Tyng-An , Angeli Veronique , Blander J. Magarian , Choi Kyunghee , Dalod Marc , Dzhagalov Ivan , Gautier Emmanuel L. , Jakubzick Claudia , Lavine Kory , Lionakis Michail S. , Paidassi Helena , Sieweke Michael H. , Ginhoux Florent , Guilliams Martin , Benoist Christophe , Merad Miriam , Randolph Gwendalyn J. , Sergushichev Alexey , Artyomov Maxim N. ,   ImmGen Consortium
Published: July 2020

AbstractWe dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cellsin vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes.
Production of moth sex pheromones for pest control by yeast fermentation
Authors: Holkenbrink Carina , Ding Bao-Jian , Wang Hong-Lei , Dam Marie Inger , Petkevicius Karolis , Kildegaard Kanchana Rueksomtawin , Wenning Leonie , Sinkwitz Christina , Lorántfy Bettina , Koutsoumpeli Eleni , França Lucas , Pires Marina , Bernardi Carmem , Urrutia William , Mafra-Neto Agenor , Ferreira Bruno Sommer , Raptopoulos Dimitris , Konstantopoulou Maria , Löfstedt Christer , Borodina Irina 
Published: July 2020

AbstractThe use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations.1,2Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits.3Here we demonstrate a biotechnological method for the production of pheromones of economically important moth pests using engineered yeast cell factories. Biosynthetic pathways towards several pheromones or their precursors were reconstructed in the oleaginous yeastYarrowia lipolytica, which was further metabolically engineered for improved pheromone biosynthesis by decreasing fatty alcohol degradation and downregulating storage lipid accumulation. The sex pheromone of the cotton bollwormHelicoverpa armigerawas produced by oxidation of fermented fatty alcohols into corresponding aldehydes. The resulting pheromone was just as efficient and specific for trapping ofH. armigeramale moths in cotton fields in Greece as a synthetic pheromone mixture. We further demonstrated the production of the main pheromone component of the fall armywormSpodoptera frugiperda. Our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control by yeast fermentation.Significance statementAgriculture largely relies on insecticides and genetically modified crops for pest control, however alternative solutions are required due to emerging resistance, toxicity and regulatory issues, and consumer preferences. Mating disruption with sex pheromones that act by preventing insect reproduction is considered the most promising and scalable alternative to insecticides. This method is highly efficient and safe for human health and environment. The likelihood of insect resistance development is very low and can be handled by adjusting the pheromone composition. The high cost of chemically synthesized pheromones is the major barrier for the wider adoption of pheromones. A novel method based on yeast fermentation enables the production of insect sex pheromones as a lower cost from renewable feedstocks.
Concurrent visual working memory bias in sequential integration of approximate number
Authors: Kang Zhiqi , Spitzer Bernhard 
Published: July 2020

AbstractPrevious work has shown bidirectional crosstalk between Working Memory (WM) and perception such that the contents of WM can alter concurrent percepts and vice versa. Here, we examine WM-perception interactions in a new task setting. Participants judged the proportion of colored dots in a stream of visual displays while concurrently holding location- and color information in memory. Spatiotemporally resolved psychometrics disclosed a modulation of perceptual sensitivity consistent with a bias of visual spatial attention towards the memorized location. However, this effect was short-lived, suggesting that the visuospatial WM information was rapidly deprioritized during processing of new perceptual information. Independently, we observed robust bidirectional biases of categorical color judgments, in that perceptual decisions and mnemonic reports were attracted to each other. These biases occurred without reductions in overall perceptual sensitivity compared to control conditions without a concurrent WM load. The results conceptually replicate and extend previous findings in visual search and suggest that crosstalk between WM and perception can arise at multiple levels, from sensory-perceptual to decisional processing.
Methylation-Based Age Estimation in a Wild Mouse
Authors: Little Tom J. , O’Toole Aine N. , Rambaut Andrew , Chandra Tamir , Marioni Riccardo , Pedersen Amy B. 
Published: July 2020

AbstractThe age structure of populations, or the ageing rate of individuals, impacts aspects of ecology, epidemiology and conservation. Yet for many wild organisms, age is an inaccessible trait. In many cases measuring age or ageing rates in the wild requires molecular biomarkers of age. Epigenetic clocks based on DNA methylation have been shown to accurately estimate the age of humans and laboratory mice, but they also show variable ticking rates that are associated with mortality risk above and beyond that predicted by chronological age. Thus, epigenetic clocks are proving to be useful markers of both chronological and biological age, and they are beginning to be applied to wild mammals and birds. We have acquired strong evidence that an accurate clock is possible for the wood mouseApodemus sylvaticusby adapting epigenetic information from the laboratory mouse (Mus musculus).Apodemus sylvaticus isa well-studied, common small mammal in the UK and Europe, which is amenable to large-scale experimental perturbations and longitudinal sampling of individuals across their lives. These features of the wood mouse system offer opportunities to disentangle causal relationships between ageing rates and environmental stress. Our wood mouse epigenetic clock is PCR-based, and so requires only tiny amounts of tissue accessible through non-destructive sampling. We quantified methylation using Oxford Nanopore sequencing technology and present a new bioinformatics pipeline for data analysis. We thus describe a new and generalizable system that should enable ecologists and other field biologists to go from small tissue samples to an epigenetic clock for their study animal, which will enable investigations of ageing in the wild which where previously inaccessible.
High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells
Authors: Ma Yayao , Lee Youngjae , Best-Popescu Catherine , Gao Liang 
Published: July 2020

AbstractWe present high-resolution, high-speed fluorescence lifetime imaging microscopy (FLIM) of live cells based on a compressed sensing scheme. By leveraging the compressibility of biological scenes in a specific domain, we simultaneously record the time-lapse fluorescence decay upon pulsed laser excitation within a large field of view. The resultant system, referred to as compressed FLIM, can acquire a widefield fluorescence lifetime image within a single camera exposure, eliminating the motion artifact and minimizing the photobleaching and phototoxicity. The imaging speed, limited only by the readout speed of the camera, is up to 100 Hz. We demonstrated the utility of compressed FLIM in imaging various transient dynamics at the microscopic scale.
An ancient deletion in the ABO gene affects the composition of the porcine microbiome by altering intestinal N-acetyl-galactosamine concentrations
Authors: Yang Hui , Wu Jinyuan , Huang Xiaochang , Zhou Yunyan , Zhang Yifeng , Liu Min , Liu Qin , Ke Shanlin , He Maozhang , Fu Hao , Fang Shaoming , Xiong Xinwei , Jiang Hui , Chen Zhe , Wu Zhongzi , Gong Huanfa , Tong Xinkai , Huang Yizhong , Ma Junwu , Gao Jun , Charlier Carole , Coppieters Wouter , Shagam Lev , Zhang Zhiyan , Ai Huashui , Yang Bin , Georges Michel , Chen Congying , Huang Lusheng 
Published: July 2020

SummaryWe have generated a large heterogenous stock population by intercrossing eight divergent pig breeds for multiple generations. We have analyzed the composition of the intestinal microbiota at different ages and anatomical locations in > 1,000 6th- and 7th- generation animals. We show that, under conditions of exacerbated genetic yet controlled environmental variability, microbiota composition and abundance of specific taxa (includingChristensenellaceae) are heritable in this monogastric omnivore. We fine-map a QTL with major effect on the abundance ofErysipelotrichaceaeto chromosome 1q and show that it is caused by a common 2.3-Kb deletion inactivating the ABO acetyl-galactosaminyl-transferase gene. We show that this deletion is a trans-species polymorphism that is ≥3.5 million years old and under balancing selection. We demonstrate that it acts by decreasing the concentrations of N-acetyl-galactosamine in the cecum thereby reducing the abundance ofErysipelotrichaceaestrains that have the capacity to import and catabolize N-acetyl-galactosamine.
Using SNAP-tag for facile construction of dye-based biosensors in living cells
Authors: Pinkin Nicholas K. , Liu Bei , Pimenta Frederico M. , Hahn Klaus M. 
Published: July 2020

AbstractFluorescent biosensors based on environment-sensitive dyes have important advantages over alternative methodologies such as FRET, including the potential for enhanced brightness, elimination of bleaching artifacts, and more possibilities for multiplexing. However, such biosensors have been difficult to use because they required proteins to be covalently labeled and reintroduced into cells. Recent development of self-labeling enzymes that covalently react with membrane-permeable dyes (e.g. SNAP-tag) provide an opportunity to easily generate dye-based biosensors within cells. Here, we generate a new biosensor for Cdc42 activation by positioning SNAP-tag between Cdc42 and a peptide that binds selectively to active Cdc42. We generate a membrane-permeable Nile Red derivative that exhibits 50-fold fluorescence enhancement upon covalent labeling of the biosensor, then optimize the biosensor so the dye undergoes a 20 nm emission shift upon Cdc42 activation, enabling ratiometric imaging with a single dye. The biosensor, named SNAPsense Cdc42, is validated by examining its response to known regulatory proteins and studying Cdc42 activation during protrusion in living cells. Variants using other dyes are also presented.
Early life nociception is influenced by peripheral growth hormone signaling
Authors: Dourson Adam J. , Ford Zachary K. , Green Kathryn J. , McCrossan Carolyn E. , Hofmann Megan C. , Hudgins Renita C. , Jankowski Michael P. 
Published: July 2020

AbstractA number of cellular systems work in concert to modulate nociceptive processing in the periphery, but the mechanisms that regulate neonatal nociception may be distinct compared to adults. Our previous work indicated a relationship between neonatal hypersensitivity and growth hormone (GH) signaling. Here, we explored the peripheral mechanisms by which GH modulated neonatal nociception under normal and injury conditions (incision). We found that GH receptor signaling in primary afferents maintains a tonic inhibition of peripheral hypersensitivity. After injury, a macrophage dependent displacement of injury-site GH was found to modulate neuronal transcription at least in part via serum response factor regulation. A single GH injection into the injured hindpaw muscle effectively restored available GH signaling to neurons and prevented acute pain-like behaviors, primary afferent sensitization, and neuronal gene expression changes. GH treatment also inhibited long-term somatosensory changes observed after repeated peripheral insult. Results may indicate a novel mechanism of neonatal nociception.Significance statementAlthough it is noted that mechanisms of pain development in early life are unique compared to adults, little research focuses on neonatal-specific peripheral mechanisms of nociception. This gap is evident in the lack of specialized care for infants following an injury including surgeries. This report evaluates how distinct cellular systems in the periphery including the endocrine, immune and nervous systems work together to modulate neonatal-specific nociception. We uncovered a novel mechanism by which muscle injury induces a macrophage-dependent sequestration of peripheral growth hormone that effectively removes its normal tonic inhibition of neonatal nociceptors to promote acute pain-like behaviors. Results indicate a possible new strategy for treatment of neonatal post-surgical pain.
Application of deep neural network reveals novel effects of maternal pre-conception exposure to nicotine on rat pup behavior
Authors: Torabi Reza , Jenkins Serena , Harker Allonna , Whishaw Ian Q. , Gibb Robbin , Luczak Artur 
Published: July 2020

AbstractWe present a deep neural network for data-driven analyses of infant rat behavior in an open field task. The network was applied to study the effect of maternal nicotine exposure prior to conception on offspring motor development. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams versus control dams. Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in “warm-up” behavior (the initiation of movement along specific dimensions) that were predictive of nicotine exposure. The results suggest that maternal preconception nicotine exposure delays and alters offspring motor development. In summary, we demonstrated that a deep neural network can automatically assess animal behavior with high accuracy, and that it offers a data-driven approach to investigating pharmacological effects on brain development.SignificanceRelating neuronal activity to behavior is crucial to understand brain function. Despite the staggering progress in monitoring brain activity, behavioral analyses still do not differ much from methods developed 30-50 years ago. The reason for that is the difficulty for automated video analyses to detect small differences in complex movements. Here we show that applying deep neuronal networks for automated video analyses can help to solve this problem. More importantly, knowledge extracted from the network allowed to identify subtle changes in multiple behavioral components, which were caused by maternal preconception nicotine exposure in rat pups. Thus, the examples presented here show how neuronal networks can guide the development of more accurate behavioral tests to assess symptoms of neurological disorders.
Strain-level analysis ofBifidobacterium spp. from gut microbiomes of adults of differing lactase persistence genotypes
Authors: Schmidt Victor , Enav Hagay , Spector Timothy , Youngblut Nicholas D. , Ley Ruth 
Published: July 2020

ABSTRACTOne of the strongest associations between human genetics and the gut microbiome is a greater relative abundance ofBifidobacteriumin adults with lactase gene(LCT)SNPs associated with lactase-non persistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with varying lactase persistence genotypes. We further employed a novel genome-capture based enrichment ofBifidobacteriumDNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times.B. adolescentisandB. longumwere the most abundantBifidobacteriumspecies regardless of hostLCT-genotype.LCT-genotypes could not be discriminated based on relative abundances ofBifidobacteriumspecies orBifidobacteriumcommunity structure. Metagenomic analysis ofBifidobacterium-enrichedDNA revealed intra-individual temporal stability ofB. longum, B. adolescentis,andB. bifidumstrains against the background of a changeable microbiome. We also observed greater strain sharing within MZ twin pairs compared to unrelated individuals, and within GG compared to AA/AG individuals, but no effect of hostLCTgenotype onBifidobacteriumstrain composition. Our results support a “rising tide lift all boats” model for the dominant Bifidobacteria in the adult gut: their higher abundance in lactase-non persistent compared to lactase-persistent individuals results from an expansion at the genus level.Bifidobacteriumspecies are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.IMPORTANCEWhen human populations domesticated animals to drink their milk they adapted genetically with the ability to digest milk into adulthood (lactase persistence). The gut microbiomes of lactase non-persistent people (LNP) differ from those of lactase-persistent people (LP) by containing more bacteria belonging to the Bifidobacteria. These beneficial gut bacteria, which fall into many species, are known to degrade milk in the baby gut. Here, we asked if adult LP and LNP microbiomes differ in the species of Bifidobacteria present. We studied the gut microbiomes of LP and LNP adults, including twins, sampled at several times. In particular, we used a technique to selectively pull out the DNA belonging to the Bifidobacteria: analysis of these DNA segments allowed us to compare Bifidobacteria at the strain level. Our results show that the LNP enhance the abundance of Bifidobacteria regardless of species. We also noted that a person’s specific strains are recoverable several years later, and twins tend to share the same ones. Given that Bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long term, multi-generational inheritance.