bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short term tomato consumption alters the pig gut microbiome towards a more favorable profile
Authors: Goggans Mallory L. , Bilbrey Emma A. , Quiroz-Moreno Cristian , Francis David M. , Jacobi Sheila K. , Kovac Jasna , Cooperstone Jessica L. 
Published: May 2022

ABSTRACTDiets rich in fruits and vegetables have been shown to exert positive effects on the gut microbiome. However, little is known about the specific effect of individual fruits or vegetables on gut microbe profiles. This study aims to elucidate the effects of tomato consumption on the gut microbiome, as tomatoes account for 22% of vegetable consumption in Western diets, and their consumption has been associated with positive health outcomes. Using piglets as a physiologically relevant model of human metabolism, 20 animals were assigned either to a control or tomato powder supplemented diet (both macronutrient matched and isocaloric) for 14 days. The microbiome was sampled rectally at three time points: day 0 (baseline), day 7 (midpoint), and at day 14 (end of study). DNA was sequenced using shotgun metagenomics, and reads were annotated using MG-RAST. There were no differences in body weight or feed intake between our two treatment groups. There was a microbial shift which included a higher ratio of Bacteroidota to Bacillota (formerly known as Bacteroidetes and Firmicutes, respectively) and higher alpha-diversity in tomato-fed animals, indicating a shift to a more desirable phenotype. Analyses at both the phyla and genera levels showed global microbiome profile changes (PERMANOVA P ≤ 0.05) over time, but not with tomato consumption. These data suggest that short-term tomato consumption can beneficially influence the gut microbial profile, warranting further investigation in humans.IMPORTANCEThe composition of the microorganisms in the gut is a contributor to overall health, prompting the development of strategies to alter the microbiome composition. Studies have investigated the role of the diet on the microbiome, as it is a major modifiable risk factor contributing to health; however, little is known about the causal effects of consumption of specific foods on the gut microbiota. A more complete understanding of how individual foods impact the microbiome will enable more evidence-based dietary recommendations for long-term health. Tomatoes are of interest as the most consumed non-starchy vegetable and a common source of nutrients and phytochemicals across the world. This study aimed to elucidate the effect of short-term tomato consumption on the microbiome, using piglets as a physiologically relevant model to humans. We found that tomato consumption can positively affect the gut microbial profile, which warrants further investigation in humans.
Transcriptome analysis in the silkworm Bombyx mori overexpressing piRNA-resistant Masculinizer gene
Authors: Tomihara Kenta , Katsuma Susumu , Kiuchi Takashi 
Published: May 2022

AbstractDosage compensation is a process that produces a similar expression of sex-linked and autosomal genes. In the silkworm Bombyx mori with a WZ sex-determination system, the expression from the single Z in WZ females matches that of ZZ males due to the suppression of Z-linked genes in males. A primary maleness determinant gene, Masculinizer (Masc), is also required for dosage compensation. In females, P-element induced wimpy testis (PIWI) is complexed with the W chromosome-derived female-specific Feminizer (Fem) PIWI-interacting RNA (piRNA) and cleaves Masc mRNA. When Fem piRNA-resistant Masc cDNA (Masc-R) is overexpressed in both sexes, only female larvae are dead during the larval stage. In this study, transcriptome analysis was performed in neonate larvae to examine the effects of Masc-R overexpression on a global gene expression profile. Z-linked genes were globally repressed in Masc-R-overexpressing females due to force-driven dosage compensation. In contrast, Masc-R overexpression had little effect on the expression of Z-linked genes and the male-specific isoform of B. mori insulin-like growth factor II mRNA-binding protein in males, indicating that excessive Masc expression strengthens neither dosage compensation nor maleness in males. Fourteen genes were differentially expressed between Masc-R-overexpressing and control neonate larvae in both sexes, suggesting Masc functions other than dosage compensation and masculinization.HighlightsTranscriptome analysis was performed in Masc-R-overexpressing neonate Bombyx mori larvae.Z-linked genes were globally suppressed in Masc-R-overexpressing females.Masc-R overexpression had little effect on BmImpM expression in males.Several genes may be controlled by Masc-R regardless of sex.
Dandy Walker-like malformations in mutant mice demonstrate a role for PDGF-C/PDGFRα signalling in cerebellar development
Authors: Gillnäs Sara , Gallini Radiosa , He Liqun , Betsholtz Christer , Andrae Johanna 
Published: May 2022

AbstractFormation of the mouse cerebellum is initiated in the embryo and continues for a few weeks after birth. Double mutant mice lacking platelet-derived growth factor-C and that are heterozygous for platelet-derived growth factor receptor alpha (Pdgfc-/-; PdgfraGFP/+) develop cerebellar hypoplasia and malformation with loss of cerebellar lobes in the posterior vermis. This phenotype is similar to those observed in Foxc1 mutant mice and the human syndrome Dandy Walker malformation. Pdgfc-Pdgfra mutant mice also display ependymal denudation in the 4th ventricle and gene expression changes in cerebellar meninges, which coincide with the first visible signs of cerebellar malformation. Our observations suggest that PDGF-C/PDGFRα signalling is a critical component of the network of molecular and cellular interactions that take place between the developing meninges and neural tissues, and which are required to build a fully functioning cerebellum.Summary statementMice lacking PDGF-C develop cerebellar hypoplasia and malformation. In addition, the ventricular zone close to the rhombic lip suffer from ependymal denudation.
The Smc5/6 complex is a DNA loop extruding motor
Authors: Pradhan Biswajit , Kanno Takaharu , Igarashi Miki Umeda , Baaske Martin Dieter , Kei Wong Jan Siu , Jeppsson Kristian , Björkegren Camilla , Kim Eugene 
Published: May 2022

AbstractStructural Maintenance of Chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes. While cohesin and condensin organize chromosomes by extruding DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown. Using single-molecule imaging, we reveal that Smc5/6 forms DNA loops by extrusion. Upon ATP-hydrolysis, Smc5/6 symmetrically reels DNA into loops at a force-dependent rate of 1 kilobase pairs per second. Smc5/6 extrudes loops in the form of a dimer, while monomeric Smc5/6 unidirectionally translocate along DNA. We also find that Nse5 and Nse6 (Nse5/6) subunits act as negative regulators of Smc5/6-mediated loop initiation and stability. Our findings reveal Smc5/6’s molecular functions, and establish loop extrusion as a conserved mechanism among eukaryotic SMC complexes.One-Sentence SummarySmc5/6 is a DNA-loop-extruding motor, establishing loop extrusion as a conserved mechanism among eukaryotic SMC complexes.
Human REM sleep controls neural excitability in support of memory formation
Authors: Lendner Janna D. , Mander Bryce A. , Schuh-Hofer Sigrid , Schmidt Hannah , Knight Robert T. , Walker Matthew P. , Lin Jack , Helfrich Randolph F. 
Published: May 2022

AbstractSleep oscillations provide a key substrate to facilitate memory processing, the underlying mechanism of which may involve the overnight homeostatic regulation of plasticity at a synaptic and whole-network level. However, there remains a lack of human data demonstrating if and how sleep enhances memory consolidation and associated neural homeostasis. We combined intracranial recordings and scalp electroencephalography (EEG) in humans to reveal a new role for rapid eye movement (REM) sleep in promoting the homeostatic recalibration of optimal excitation/inhibition-balance. Moreover, the extent of this REM-sleep homeostatic recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal— neocortical excitability favoring remembering rather than forgetting. The findings describe a novel, fundamental role of human REM sleep in maintaining neural homeostasis, thereby enhancing long-term memory.
neoMS: Attention-based Prediction of MHC-I Epitope Presentation
Authors: Mill Nil Adell , Bogaert Cedric , van Criekinge Wim , Fant Bruno 
Published: May 2022

AbstractPersonalised immunotherapy aims to (re-)activate the immune system of a given patient against its tumour. It relies extensively on the ability of tumour-derived neoantigens to trigger a T-cell immune reaction able to recognise and kill the tumour cells expressing them. Since only peptides presented on the cell surface can be immunogenic, the prediction of neoantigen presentation is a crucial step of any discovery pipeline. Limiting neoantigen presentation to MHC binding fails to take into account all other steps of the presentation machinery and therefore to assess the true potential clinical benefit of a given epitope. Indeed, research has uncovered that merely 5% of predicted tumour-derived MHC-bound peptides is actually presented on the cell surface, demonstrating that affinity-based approaches fall short from isolating truly actionable neoantigens. Here, we present neoMS, a MHC-I presentation prediction algorithm leveraging mass spectrometry-derived MHC ligandomic data to better isolate presented antigens from potentially very large sets. The neoMS model is a transformer-based, peptide-sequence-to-HLA-sequence neural network algorithm, trained on 386,647 epitopes detected in the ligandomes of 92 HLA-monoallelic datasets and 66 patient-derived HLA-multiallelic datasets. It leverages attention mechanisms in which the most relevant parts of both putative epitope and HLA alleles are isolated. This results in a positive predictive value of 0.61 at a recall of 40% on its patient-derived test dataset, considerably outperforming current alternatives. Predictions made by neoMS correlate with peptide identification confidence in mass spectrometry experiments and reliably identify binding motif preferences of individual HLA alleles thereby further consolidating the biological relevance of the model. Additionally, neoMS displays extrapolation capabilities, showing good predictive power for presentation by HLA alleles not present in its training dataset. Finally, it was found that neoMS results can help refine predictions of response to immune checkpoint inhibitor treatment in certain cancer indications. Taken together, these results establish neoMS as a considerable step forward in high-specificity isolation of clinically actionable antigens for immunotherapies.
Genes ruler for genomes, Gnodes, measures assembly accuracy in animals and plants
Authors: Gilbert Donald G. 
Published: May 2022

AbstractGnodes is a Genome Depth Estimator for animal and plant genomes, also a genome size estimator. It calculates genome sizes based on DNA coverage of assemblies, using unique, conserved gene spans for its standard depth. Results of this tool match the independent measures from flow cytometry of genome size quite well in tests with plants and animals. Tests on a range of model and non-model animal and plant genome assemblies give reliable and accurate results, in contrast to less reliable K-mer histogram methods. The problem of half-sized assemblies of duplication-rich Daphnia is addressed. A 20-year old Arabidopsis genome discrepancy is resolved in favor of 157Mb as measured with flow-cytometry. Not all genome DNA samples contain a genome, examples and reasons for this are discussed. The T2T completed human genome assembly of 2022 is complete by Gnodes measures, with about 5% uncertainty. With full genome DNA, Gnodes measures within 10%, usually within 5%, of flow cytometry, indicating they are both measuring the same content. Public URL: http://eugenes.org/EvidentialGene/other/gnodes/
Active licking shapes cortical taste coding
Authors: Neese Camden , Bouaichi Cecilia G. , Needham Tom , Bauer Martin , Bertram Richard , Vincis Roberto 
Published: May 2022

AbstractNeurons in the gustatory cortex (GC) represent taste through time-varying changes in their spiking activity. The predominant view is that the neural firing rate represents the sole unit of taste information. It is currently not known whether the phase of spikes relative to lick timing is used by GC neurons for taste encoding. To address this question, we recorded spiking activity from >500 single GC neurons in male and female mice permitted to freely lick to receive four liquid gustatory stimuli and water. We developed a set of data analysis tools to determine the ability of GC neurons to discriminate gustatory information and then to quantify the degree to which this information exists in the spike rate versus the spike timing or phase relative to licks. These tools include machine learning algorithms for classification of spike trains and methods from geometric shape and functional data analysis. Our results show that while GC neurons primarily encode taste information using a rate code, the timing of spikes is also an important factor in taste discrimination. A further finding is that taste discrimination using spike timing is improved when the timing of licks is considered in the analysis. That is, the interlick phase of spiking provides more information than the absolute spike timing itself. Overall, our analysis demonstrates that the ability of GC neurons to distinguish among tastes is best when spike rate and timing is interpreted relative to the timing of licks.Significance StatementNeurons represent information from the outside world via changes in their number of action potentials (spikes) over time. This study examines how neurons in the mouse gustatory cortex (GC) encode taste information when gustatory stimuli are experienced through the active process of licking. We use electrophysiological recordings and data analysis tools to evaluate the ability of GC neurons to distinguish tastants and then to quantify the degree to which this information exists in the spike rate versus the spike timing relative to licks. We show that the neuron’s ability to distinguish between tastes is higher when spike rate and timing are interpreted relative to the timing of licks, indicating that the lick cycle is a key factor for taste processing.
Disrupted Decision-Making: EcoHIV Inoculation Following a History of Cocaine Use
Authors: McLaurin Kristen A. , Li Hailong , Mactutus Charles F. , Harrod Steven B. , Booze Rosemarie M. 
Published: May 2022

SUMMARYIndependently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing a history of both sucrose and cocaine self-administration, a pretest-posttest experimental design was utilized to evaluate preference judgment, a simple form of decision-making dependent upon the integrity of frontal- striatal circuit function. During the pretest assessment, male rats exhibited a clear preference for cocaine, whereas female animals preferred sucrose. Two posttest evaluations (3 Days and 6 Weeks Post Inoculation) revealed that, independent of biological sex, inoculation with chimeric HIV (EcoHIV), but not saline, disrupted decision-making. Prominent structural alterations in frontal-striatal circuit dysfunction were evidenced by synaptodendritic alterations in pyramidal neurons in the medial prefrontal cortex. Thus, the EcoHIV rat affords a biological system to model how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use.
Cysteine Restriction-Specific Effects of Sulfur Amino Acid Restriction on Lipid Metabolism
Authors: Nichenametla Sailendra N , Mattocks Dwight AL , Cooke Diana , Midya Vishal , Malloy Virginia L , Mansilla Wilfredo , Øvrebø Bente , Turner Cheryl , Bastani Nasser E , Sokolová Jitka , Pavlíková Markéta , Richie John P , Shoveller Anna K , Refsum Helga , Olsen Thomas , Vinknes Kathrine J , Kožich Viktor , Ables Gene P 
Published: May 2022

SummaryDecreasing dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), i.e., sulfur amino acid restriction (SAAR). Contrarily, human diets used in clinical studies did not eliminate cysteine and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not with methionine, suggesting that CR, but not MR, is responsible for the antiadiposity effects of SAAR in rodents. Whether this is true, and if so, the underlying mechanisms are unknown. Using multiple diets with variable concentrations of methionine and cysteine, we demonstrate that the anti-adiposity effects of SAAR are due to CR. CR increased serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, essential for fatty acid/triglyceride cycling. Molecular data suggest that the CR results in glutathione depletion, which induces Nrf2 and downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. Using multiple mouse models, we show that the magnitude of SAAR-induced changes in molecular markers depends on dietary fat concentration (60 fat>10% fat), gender (males>females), and age-at-onset (young>adult). Our findings are translationally relevant as we found a negative correlation of plasma serine with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. SAAR-like diets with high polyunsaturated fatty acids increased plasma serine in a short-term human feeding study. Serinogenesis might be a potential target to correct hypertriglyceridemia.
Solubility-aware protein binding peptide design using AlphaFold
Authors: Kosugi Takatsugu , Ohue Masahito 
Published: May 2022

AbstractNew protein–protein interactions (PPIs) are being identified, but PPIs have different physicochemical properties compared with conventional targets, making it difficult to use small molecules. Peptides offer a new modality to target PPIs, but designing appropriate peptide sequences by computation is challenging. Recently, AlphaFold and RosettaFold have made it possible to predict protein structures from amino acid sequences with ultra-high accuracy, enabling de novo protein design. We designed peptides likely to have PPI as the target protein using the “binder hallucination” protocol of AfDesign, a de novo protein design method using AlphaFold. However, the solubility of the peptides tended to be low. Therefore, we designed a solubility loss function using solubility indices for amino acids and developed a solubility-aware AfDesign binder hallucination protocol. The peptide solubility in sequences designed using the new protocol increased with the weight of the solubility loss function; moreover, they captured the characteristics of the solubility indices. Moreover, the new protocol sequences tended to have higher affinity than random or single residue substitution sequences when evaluated by docking binding affinity. Our approach shows that it is possible to design peptide sequences that can bind to the interface of PPI while controlling solubility.
The ClpP Peptidase Forcefully Grips Protein Substrates
Authors: Walker Steven D. , Olivares Adrian O. 
Published: May 2022

ABSTRACTATPases Associated with diverse cellular Activities (AAA+) proteases power the maintenance of protein homeostasis by coupling ATP hydrolysis to mechanical protein unfolding, translocation, and ultimately degradation. Though ATPase activity drives a large portion of the mechanical work these molecular machines perform, how the peptidase contributes to the forceful denaturation and processive threading of substrates remains unknown. Here, using single-molecule optical trapping, we examine the mechanical activity of the Caseinolytic Peptidase P (ClpP) from Escherichia coli in the absence of a partner ATPase and in the presence of an activating small molecule acyldepsipeptide. We demonstrate that ClpP grips protein substrate under mechanical loads exceeding 40 pN, which are greater than those observed for the AAA+ unfoldase ClpX and the AAA+ protease complexes ClpXP and ClpAP. We further characterize substrate-ClpP bond lifetimes and rupture forces under varying loads. We find that the resulting slip bond behavior does not depend on ClpP peptidase activity. Additionally, we find that unloaded bond lifetimes between ClpP and protein substrate are on a timescale relevant to unfolding times (up to ∼160 s) for difficult to unfold model substrate proteins. These direct measurements of the substrate-peptidase bond under load define key properties required by AAA+ proteases to mechanically unfold and degrade protein substrates.STATEMENT OF SIGNIFICANCEEnergy-dependent proteases drive essential protein degradation to maintain cellular homeostasis and to rapidly regulate protein levels in response to changes in cellular environment. Using single-molecule optical tweezers, several studies demonstrate that the molecular process of degradation involves the mechanical unfolding and translocation of protein substrates by the ATP hydrolyzing enzyme component of these protease complexes. This study provides evidence that the chambered peptidase component of these molecular machines also contributes to the mechanical process of degradation by gripping substrate under load in a manner independent of peptide hydrolysis. Our results suggest that the peptidase actively contributes to the biophysical mechanisms underlying processive protein degradation by energy-dependent proteolytic machines.