bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Optimal Regulation of Fluxes Dictates Microbial Growth In and Out of Steady-State
Authors: Chure Griffin , Cremer Jonas 
Published: January 2022

AbstractEffective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic control of this resource partitioning. At the core of this regulation is the optimal coordination of metabolic and translational fluxes, mechanistically achieved via the perception of charged- and uncharged-tRNA turnover. An extensive comparison with ≈ 60 data sets fromEscherichia coliestablishes this regulatory mechanism’s biological veracity and demonstrates that a remarkably wide range of growth phenomena in and out of steady state can be predicted with quantitative accuracy. This predictive power, achieved with only a few biological parameters, cements the preeminent importance of optimal flux regulation across conditions and establishes low-dimensional allocation models as an ideal physiological framework to interrogate the dynamics of growth, competition, and adaptation in complex and ever-changing environments.
Development of DNA methylation-based epigenetic age predictors in loblolly pine (Pinus taeda)
Authors: Gardner Steven T. , Bertucci Emily M. , Sutton Randall , Horcher Andy , Aubrey Doug , Parrott Benjamin B. 
Published: January 2022

AbstractBiological aging is connected to life history variation across ecological scales, as well as informing a basic understanding of age-related declines to organismal function. Altered DNA methylation dynamics are a conserved aspect of biological aging and have recently been modeled to predict chronological age among vertebrate species. In addition to their utility in estimating individual age, differences between chronological and predicted ages arise due to acceleration or deceleration of epigenetic aging, and these discrepancies are linked to disease risk and multiple life history traits. Although evidence suggests that patterns of DNA methylation can describe aging in plants, predictions with epigenetic clocks have yet to be performed. Here, we resolve the DNA methylome across CpG, CHG, and CHH-methylation contexts in the loblolly pine tree (Pinus taeda) and construct epigenetic clocks capable of predicting ages in this species within 8% of its lifespan. Although patterns of CHH methylation showed little association with age, both CpG and CHG methylation contexts were strongly associated with aging, largely becoming hypomethylated with age. Among age-associated loci were those in close proximity to malate dehydrogenase, NADH dehydrogenase, and 18S and 26S ribosomal RNA genes. This study reports one of the first epigenetic clocks in plants and demonstrates the universality of age-associated DNA methylation dynamics which can inform conservation and management practices, as well as our ecological and evolutionary understanding of biological aging in plants.
A novel bacteriocin produced byBifidobacterium longumsubsp.infantishas dual antimicrobial and immunomodulatory activity
Authors: Javvadi Sree Gowrinadh , Kujawska Magdalena , Papp Diana , Gontarczyk Aleksander M , Jordan Anne , Lawson Melissa A.E. , O’Neill Ian J. , Alcon-Giner Cristina , Kiu Raymond , Clarke Paul , Beraza Naiara , Hall Lindsay J 
Published: January 2022

AbstractBacteriocins are ribosomally-synthesized antimicrobial peptides produced by bacteria with either narrow or broad spectrum activity. Many genome mining studies have indicated that bacteriocin gene clusters are widespread within certain gut microbiota members. In early life,Bifidobacteriumcomprise the dominant microbiota genus in vaginally delivered and breast-fed infants, with high levels associated with improved health. However, in many cases the mechanisms underlying these beneficial effects are unknown, although a limited number of studies have suggested that bacteriocin production byBifidobacteriummay represent a key mechanism for preventing pathogen over-growth. Here, we used BAGEL4 and antiSMASH to identify putative bacteriocin sequences in the whole genome sequences of 33Bifidobacteriumstrains isolated from infants participating in two clinical studies. We identified a novel non-lantibiotic bacteriocin fromBifidobacterium longumsubsp.infantisLH_664, with 40% sequence homology to Lactococcin 972 fromLactococcus lactissubsp.lactis. The putative bacteriocin (Bifidococcin_664) was chemically synthesized and studied for antimicrobial and immune-modulatory activities. We determined it has discrete activity againstClostridium perfringensand it appears to have novel immune stimulatory activities, promoting macrophage phagocytosis and specific cytokine release. These data highlight strain-specific beneficial properties in the early life genusBifidobacterium, and suggest avenues for development of novel and highly specific dual action antimicrobials, and possible probiotic strains, that are active against clinically important bacterial pathogens.Data summarySamples LH_9 to LH_666 were previously sequenced and deposited to ENA under accession numbers ERS2658025-ERS2658043. Samples LH_986 to LH_1052 are newly sequenced and deposited to NCBI under accession numbers SAMN24838598-SAMN24838611. Additionally, previously assembled publicly available sequences (n=7) were retrieved online from NCBI Genomes database. See Supplementary Table S1 for further details.
Genetic characterization of ABC pesticide transporters establishes Drosophila as an in vivo model for toxicogenetics
Authors: Denecke Shane , Lương Hằng Ngọc Bao , Koidou Venetia , Kalogeridi Maria , Socratous Rafaella , Howe Steven , Vogelsang Kathrin , Nauen Ralf , Batterham Phil , Geibel Sven , Vontas John 
Published: January 2022

AbstractPesticides remain one of the most effective ways of controlling agricultural and public health insects, but much is still unknown regarding how these compounds reach their targets. Specifically, the role of ABC transporters in pesticide absorption and excretion is poorly understood, especially compared to the detailed knowledge in mammalian systems. Here, we present a comprehensive characterization of pesticide transporters in the model insect D. melanogaster. An RNAi screen was performed, which knocked down individual ABCs in targeted epithelial tissue, examining the subsequent changes in sensitivity to the pesticides spinosad and fipronil. This simultaneously implicated a novel ABC drug transporter CG4562 but also highlighted a predominant role for the P-glycoprotein orthologue Mdr65. Further characterization of the P-glycoprotein family was performed via transgenic overexpression and immunolocalization, finding that Mdr49 and Mdr50 play enigmatic roles in pesticide toxicology perhaps determined by their different subcellular localizations within the midgut. Lastly, heterologous expression of the Mdr65 orthologue from the major malaria vector Anopheles gambiae was used to establish an in vivo characterization system for the characterization of P-glycoproteins from non-model insects in D. melanogaster. This study provides the basis for establishing Drosophila as a model for toxicology research regarding drug transporters.
Acute Axon Damage and Demyelination are Mitigated by 4-Aminopyridine (4-AP) Therapy after Experimental Traumatic Brain Injury
Authors: Radomski Kryslaine L. , Zi Xiaomei , Lischka Fritz W. , Noble Mark D. , Galdzicki Zygmunt , Armstrong Regina C. 
Published: January 2022

ABSTRACTDamage to long axons in white matter tracts is a major pathology in closed head traumatic brain injury (TBI). Acute TBI treatments are needed that protect against axon damage and promote recovery of axon function to prevent long term symptoms and neurodegeneration. Our prior characterization of axon damage and demyelination after TBI led us to examine repurposing of 4-aminopyridine (4-AP), an FDA-approved inhibitor of voltage-gated potassium (Kv) channels. 4-AP is currently indicated to provide symptomatic relief for patients with chronic stage multiple sclerosis, which involves axon damage and demyelination. We tested clinically relevant dosage of 4-AP as an acute treatment for experimental TBI and found multiple benefits in corpus callosum axons. This randomized, controlled pre-clinical study focused on the first week after TBI, when axons are particularly vulnerable. 4-AP treatment initiated one day post-injury dramatically reduced axon damage detected by intra-axonal fluorescence accumulations in Thy1-YFP mice of both sexes. Detailed electron microscopy in C57BL/6 mice showed that 4-AP reduced pathological features of mitochondrial swelling, cytoskeletal disruption, and demyelination. Furthermore, 4-AP improved the molecular organization of axon nodal regions by restoring disrupted paranode domains and reducing Kv1.2 channel dispersion. 4-AP treatment did not resolve deficits in action potential conduction across the corpus callosum, based on ex vivo electrophysiological recordings at 7 days post-TBI. Thus, this first study of repurposing 4-AP as an acute treatment for TBI demonstrates pre-clinical efficacy in decreasing pathological hallmarks of axon damage. Studies beyond this acute phase are now warranted to assess functional utility and outcome trajectory.SIGNIFICANCE STATEMENTTraumatic brain injury (TBI) is an acute injury that, if unresolved, can progress to cause persistent, debilitating symptoms. Currently, no treatments effectively prevent damage to long myelinated axons in white matter tracts, which is a hallmark pathology of TBI. 4-aminopyridine (4-AP) is FDA-approved to treat chronic symptoms in patients with multiple sclerosis, which involves autoimmune damage to myelinated axons. As the first assessment of repurposing 4-AP as an acute treatment for TBI, our randomized, controlled studies tested the hypothesis that low-dose 4-AP initiated one day after experimental TBI will reduce acute axon damage and demyelination. We found that 4-AP treatment significantly reduced the progression of axon pathology and demyelination during the first week after TBI using clinically relevant experimental conditions.
Nascent peptide-induced translation discontinuation in eukaryotes impacts biased amino acid usage in proteomes
Authors: Ito Yosuke , Chadani Yuhei , Niwa Tatsuya , Yamakawa Ayako , Machida Kodai , Imataka Hiroaki , Taguchi Hideki 
Published: January 2022

AbstractRobust translation elongation of any given amino acid sequence is a prerequisite to shape proteomes. Nevertheless, nascent peptides could destabilize ribosomes, since consecutive negatively charged residues in bacterial nascent chains stochastically can induce discontinuation of translation, in a phenomenon termed intrinsic ribosome destabilization (IRD). Here, we show that IRD also occurs in eukaryotic translation. Nascent chains enriched in aspartic acid (D) or glutamic acid (E) in the N-terminal regions could prematurely terminate translation, producing premature products as peptidyl-tRNA species. Although eukaryotic ribosomes are more robust to ensure uninterrupted translation, we found many endogenous D/E-rich peptidyl-tRNAs in the N-terminal regions in cells lacking a peptidyl-tRNA hydrolase, indicating that the translation of the N-terminal D/E-rich sequences poses an inherent risk. Indeed, a bioinformatics analysis revealed that the N-terminal regions of ORFs avoid D/E enrichment, implying that the translation defect partly restricts the overall amino acid usage in proteomes.
Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers
Authors: Wu Shenjie , Hernandez Villegas Nancy C. , Sirkis Daniel W. , Thomas-Wright Iona , Wade-Martins Richard , Schekman Randy 
Published: January 2022

AbstractAlpha-synuclein (α-syn), a major component of Lewy bodies found in Parkinson’s disease (PD) patients, has been found exported outside of cells and may mediate its toxicity via cell-to-cell transmission. Here, we reconstituted soluble, monomeric α-syn secretion by the expression of DnaJ homolog subfamily C member 5 (DNAJC5) in HEK293T cells. DNAJC5 undergoes palmitoylation and anchors on the membrane. Palmitoylation is essential for DNAJC5-induced α-syn secretion, and the secretion is not limited by substrate size or unfolding. Cytosolic α-syn is actively translocated and sequestered in an endosomal membrane compartment in a DNAJC5-dependent manner. Reduction of α-syn secretion caused by a palmitoylation-deficient mutation in DNAJC5 can be reversed by a membrane-targeting peptide fusion-induced oligomerization of DNAJC5. The secretion of endogenous α-syn mediated by DNAJC5 is also found in a human neuroblastoma cell line, SH-SY5Y, differentiated into neurons in the presence of retinoic acid, and in human induced pluripotent stem cell-derived midbrain dopamine neurons. We propose that DNAJC5 forms a palmitoylated oligomer to accommodate and export α-syn.
Age and experience affect the biosynthesis and emission of a Drosophila pheromone
Authors: Cortot Jérôme , Farine Jean-Pierre , Cobb Matthew , Everaerts Claude , Ferveur Jean-François 
Published: January 2022

AbstractThe most studied pheromone in Drosophila melanogaster, cis-Vaccenyl Acetate (cVA), is synthesized in the male ejaculatory bulb and transferred to the female during copulation. Combined with other chemicals cVA can modulate fly aggregation, courtship, mating and fighting. It is not detected on the cuticle of isolated males and is only released by males involved in social or sexual interaction. We explored the mechanisms underlying both cVA biosynthesis and emission in males of two wild types and a pheromonal mutant line. The effects of ageing, adult social interaction, and maternally-transmitted cVa and microbes — both associated with the egg chorion— on cVA biosynthesis and emission were measured. While ageing and genotype changed both biosynthesis and emission in similar ways, early developmental exposure to maternally-transmitted cVA and microbes strongly decreased cVA emission but not the biosynthesis of this molecule. This indicates that the release — but not the biosynthesis — of this sex pheromone strongly depends on early developmental context. The mechanism by which the preimaginal effects occur is unknown, but reinforces the significance of development in determining adult physiology and behaviour.Summary statementWe show how the biosynthesis and release of a key Drosophila pheromone is affected by ageing, by early exposure to this pheromone and to microbes, and by social context.
Validation of SNP markers for marker-assisted selection of genotypes with increased carotenoid and dry matter contents in cassava
Authors: Ige Adenike D. , Olasanmi Bunmi , Bauchet Guillaume J. , Kayondo Ismail S. , Mbanjo Edwige Gaby Nkouaya , Uwugiaren Ruth , Motomura-Wages Sharon , Norton Joanna , Egesi Chiedozie , Parkes Elizabeth Y. , Kulakow Peter , Ceballos Hernan , Rabbi Ismail Y. 
Published: January 2022

AbstractProvitamin A biofortification and increased dry matter content are important breeding targets in cassava improvement programs worldwide. Biofortified varieties contribute to the alleviation of provitamin A deficiency, a leading cause of preventable blindness in developing countries. Dry matter content is a major component of dry yield and thus underlies overall variety performance and acceptability by growers, processors, and consumers. SNP markers linked to these traits have recently been discovered through several genome-wide association studies but have not been deployed for marker-assisted selection (MAS). Assessment of marker performance in diverse genetic backgrounds is an important step towards their deployment for routine MAS. In the present study, seven previously identified markers for these traits were converted to a robust set of uniplex allele-specific PCR assays and validated in two independent pre-breeding and breeding populations. These assays were efficient in discriminating marker genotypic classes and had an average call rate greater than 98%. A high correlation was observed between the predicted and observed carotenoid content as inferred by root yellowness intensity in the breeding (r = 0.92) and pre-breeding (r = 0.95) populations. On the other hand, dry matter content-markers had moderately low predictive accuracy in both populations (r < 0.40) due to the more quantitative nature of the trait. This work confirmed marker effectiveness in multiple backgrounds, therefore, further strengthening its value in cassava biofortification to ensure nutritional security as well as dry matter content productivity. Our study provides a framework to guide future marker development, thus leading to more routine use of markers in MAS in cassava improvement programs.
Sporadic Diurnal Fluctuations of Cyanobacterial Populations in Oligotrophic Temperate Systems Can Prevent Accurate Characterization of Change and Risk in Aquatic Systems
Authors: Cameron Ellen S. , Krishna Anjali , Emelko Monica B. , Müller Kirsten M. 
Published: January 2022

AbstractContinental-scale increases in aquatic system eutrophication are linked with increased cyanobacteria threats to recreational water use and drinking water resources globally. Increasing evidence suggests that diurnal vertical migration of cyanobacteria are key factors that must be considered in cyanobacterial bloom risk management. While this has been discussed in marine and eutrophic freshwater contexts, reports of diurnal vertical migration of cyanobacteria in oligotrophic freshwater lakes are scant. Typical monitoring protocols do not reflect these dynamics and frequently focus only on surface water sampling approaches, and either ignore sampling time or recommend large midday timeframes (e.g., 10AM-3PM), thereby preventing accurate characterization of cyanobacterial community dynamics. To evaluate the impact of diurnal migrations and water column stratification on cyanobacterial abundance and composition, communities were characterized in a shallow well-mixed lake interconnected to a thermally stratified lake in the Turkey Lakes Watershed (Ontario, Canada) using amplicon sequencing of the 16S rRNA gene across a multi-time point sampling series in 2018 and 2022. This work showed that cyanobacteria are present in oligotrophic lakes and their community structure varies (i) diurnally, (ii) across the depth of the water column, (iii) interannually within the same lake and (iv) between different lakes that are closely interconnected within the same watershed. It underscored the need for integrating multi-timepoint, multi-depth discrete sampling guidance into lake and reservoir monitoring programs to describe cyanobacteria community dynamics and signal change to inform risk management associated with the potential for cyanotoxin production. Ignoring variability in cyanobacterial community dynamics (such as that reported herein) and reducing sample numbers can lead to a false sense of security and missed opportunities to identify and mitigate changes in trophic status and associated risks such as toxin or taste and odor production, especially in sensitive, oligotrophic systems.Graphical AbstractHighlights■Cyanobacterial populations fluctuate sporadically across diurnal cycles■Cyanobacterial communities can vary significantly between interconnected lakes■Significant annual shifts in communities signal higher risk and need for monitoring■Cyanobacteria monitoring for risk management should incorporate time and depth
Allatotropin in the Corpora Allata and Ovaries of Rhodnius prolixus: Probable in situ regulatory mechanisms
Authors: Villalobos Sambucaro María José , Ronderos Jorge Rafael 
Published: January 2022

ABSTRACTOriginally described by Sir V. Wigglesworth in the Chagas disease vector Rhodnius prolixus, Juvenile Hormones (JHs) play critical roles during growth and reproduction. The JH described by Wigglesworth is the JH III skipped bisepoxide (JHSB3), and its titer in hemolymph varies along the 4th larval instar molting cycle. Allatotropin (AT), was originally characterized based on its ability to induce the synthesis of the JHs by the corpora allata (CA) in Lepidoptera. Beyond this function, AT has proved to be a myoregulator. Indeed, AT modulates muscle contractions in the gut, dorsal vessel and reproductive tissues. The presence of AT in the CA of 4th instar larvae of R. prolixus and the related species Triatoma infestans was previously shown, suggesting that AT might be involved in the regulation of JH synthesis in triatominae. Furthermore, the existence of allatotropic cells in this gland in T. infestans was also shown. This neuron-like cells show cytoplasmic processes projecting deeply between the cells engaged with JH synthesis. By using RT-qPCR we studied now the expression of both, AT and its receptor in the CA/CC complex along the 4th instar molting cycle, and in the ovaries of adult females. The expression of AT in the CA is highest between days 3 to 5 after meal, correlating with Mev-K and PPMev-D, two enzymes involved in the mevalonate pathway, as well as with the peak of JHSB3 on day 6. The results show that AT transcript is also present in the ovary suggesting a myoregulatory paracrine mechanism of regulation. Finally, our data suggest the existence of in situ mechanisms in the CA and ovaries of R. prolixus involving AT in both JHs synthesis and muscle contraction.
Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice
Authors: Roberts Brandon L. , Karatsoreos Ilia N. 
Published: January 2022

AbstractThe prefrontal cortex (PFC) is heavily involved in cognitive and emotional processes, including working memory, cognition, stress responses, and fear associated behaviors. Many PFC-associated behaviors are time-of-day dependent, and disruption of daily rhythms negatively impacts these behavioral outputs, yet how the disruption of daily rhythms impacts the fundamental function of PFC neurons, and the mechanism(s) by which this occurs, remains unknown. Using a mouse model, we demonstrate that the activity and action potential dynamics of prelimbic PFC neurons are regulated by time-of-day in a sex specific manner. Further, we show that postsynaptic K+channels play a central role in mediating these rhythms, suggesting an intrinsic gating mechanism mediating information throughput. Finally, we demonstrate that environmental circadian desynchronization alters the intrinsic functioning of these neurons in part by increasing sensitivity GIRK channel activation. These key discoveries demonstrate daily rhythms contribute to the mechanisms underlying the essential physiology of PFC circuits, and provide potential mechanisms by which circadian disruption may impact the fundamental properties of neurons.Significance StatementDisruption of circadian rhythms, such as shift work and jet lag, are associated with negative physiological and behavioral outcomes, including changes in affective state, cognitive function, learning and memory. The prefrontal cortex (PFC) plays a critical role in these functions, yet how daily rhythms and desynchronization of these rhythms impact the physiology of neurons in the PFC is unknown. Here we demonstrate that daily rhythms impact the physiological function of PFC neurons in a sex-dependent manner, and that environmental circadian desynchronization alters PFC function irrespective of time-of-day. These findings provide not only a physiological context to the neural and behavioral changes associated with circadian desynchronization, but also highlight the importance of considering the temporal dimension in studies of neural circuits.