bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic activation of the aryl hydrocarbon receptor in muscle exacerbates ischemic pathology in chronic kidney disease
Authors: Balestrieri Nicholas , Palzkill Victoria , Pass Caroline , Tan Jianna , Salyers Zachary R. , Moparthy Chatick , Murillo Ania , Kim Kyoungrae , Thome Trace , Yang Qingping , O’Malley Kerri A. , Berceli Scott A. , Yue Feng , Scali Salvatore T. , Ferreira Leonardo F. , Ryan Terence E. 
Published: May 2023

ABSTRACTChronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the cellular and physiological mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic toxins, many of which are ligands for the aryl hydrocarbon receptor (AHR), are associated with adverse limb outcomes in PAD. We hypothesized that chronic AHR activation, driven by the accumulation of tryptophan-derived uremic metabolites, may mediate the myopathic condition in the presence of CKD and PAD. Both PAD patients with CKD and mice with CKD subjected to femoral artery ligation (FAL) displayed significantly higher mRNA expression of classical AHR-dependent genes (Cyp1a1,Cyp1b1, andAldh3a1) when compared to either muscle from the PAD condition with normal renal function (P<0.05 for all three genes) or non-ischemic controls. Skeletal-muscle-specific AHR deletion in mice (AHRmKO) significantly improved limb muscle perfusion recovery and arteriogenesis, preserved vasculogenic paracrine signaling from myofibers, increased muscle mass and contractile function, as well as enhanced mitochondrial oxidative phosphorylation and respiratory capacity in an experimental model of PAD/CKD. Moreover, viral-mediated skeletal muscle-specific expression of a constitutively active AHR in mice with normal kidney function exacerbated the ischemic myopathy evidenced by smaller muscle masses, reduced contractile function, histopathology, altered vasculogenic signaling, and lower mitochondrial respiratory function. These findings establish chronic AHR activation in muscle as a pivotal regulator of the ischemic limb pathology in PAD. Further, the totality of the results provide support for testing of clinical interventions that diminish AHR signaling in these conditions.
Association of Muscle Strength to Body Composition Measures using DXA, D3Cr, and BIA in Collegiate Athletes
Authors: Cataldi Devon , Bennett Jonathan P. , Quon Brandon K. , Leong Lambert , Kelly Thomas L , Evans William J , Prado Carla M. , Heymsfield Steven B. , Shepherd John A 
Published: May 2023

AbstractBackgroundMeasurements of body composition are helpful indicators of health outcomes, but muscle strength has a greater correlation with disease risk and long-term health outcomes, particularly among older adults. Whole-body DXA scans uniquely parse out total and regional lean soft tissue (LST) and appendicular (ALST), primarily composed of skeletal muscle and often used to diagnose sarcopenia and frailty. An alternative approach measures the enrichment of deuterated Creatinine (D3Crn) in urine after ingesting a tracer dose of deuterated creatine (D3Cr) to determine creatine pool size and estimate whole-body muscle mass. The utility of D3Cr relationships between strength and body composition in young athletes has yet to be established. In this study, we investigated the association of muscle strength and body composition using multiple methods including DXA, D3Cr, and bioelectrical impedance (BIA), in a collegiate athletic population.MethodsTheDa KineStudy enrolled 80 multi-sport collegiate athletes. Each subject consumed a 60 mg dose of D3Cr and completed whole-body DXA, BIA, and strength tests of the leg and trunk using an isokinetic dynamometer. The analysis was stratified by sex. Pearson’s correlations, forward stepwise linear regression and quartileptrend significance were used to show the associations of body composition measures to muscle strength.ResultsThe mean (SD) age of the 80 (40M/40F) athletes was 21.8 (4.2) years. Raw whole-body values had higher correlations with muscle strength in both sexes compared to the normalized values by height, body mass (BM), and BMI. DXA LST had the highest leg (R2=0.36, 0.37) and trunk (R2=0.53, 0.61) strength in both males and females. Trunk strength was more highly associated with body composition measures than leg strength in both sexes and all measurement techniques. One or more DXA LST measures (total, leg, and ALST) were consistently more highly associated with leg and trunk strengths for both sexes than BIA and D3Cr measures. Adjusting all body composition values by age, BMI, and BIA variables did not improve the associations. A significantptrend across quartiles was observed for DXA LST and ALST for all measures of strength in both sexes.ConclusionAlthough statistical significance was not reached between devices, DXA body composition output variables, especially LST, showed the highest associations with both sexes’ leg and trunk muscle strength. Furthermore, without adjustment for demographic information or BIA variables, whole-body values show stronger associations with muscle strength. Future research should investigate the impact of muscle mass changes on LST and functional measures.
Neo-functionalization inSaccharomyces cerevisiae: A Novel Nrg1-Rtg3 chimeric transcriptional modulator is essential to maintain mitochondrial DNA integrity
Authors: Campero-Basaldua Carlos , González James , García-Rodriguez Janeth , Ramírez Edgar , Hernández Hugo , Aguirre Beatriz , Torres-Ramírez Nayeli , Márquez Dariel , Sánchez Norma , Gómez-Hernández Nicolás , Riego-Ruiz Lina , Scazzocchio Claudio , González Alicia 
Published: May 2023

AbstractInSaccharomyces cerevisiae, the transcriptional repressor Nrg1 (Negative Regulator of Glucose-repressed genes) and the b/Zip transcription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and mitochondria to nucleus signaling, respectively. Here we show a novel function for these two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses theALT2gene (encoding an alanine transaminase paralogue of unknown function) expression. ANRG1/NRG2paralogous pair, resulting from a post-wide genome, small scale duplication event, is extant in theSaccharomycesgenus. Neo-functionalization of only one paralogue resulted in Nrg1, able to interact with Rtg3. Eithernrg1Δ orrtg3Δ single mutant strains are unable to utilize ethanol and show a typical petite (small) phenotype on glucose. Neither of the WT genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neithernrg1Δ norrtg3Δ mutant strains express genes encoded by any of five polycistronic units transcribed from mitochondrial DNA inS. cerevisiae. This, and the direct measure of the mitochondrial DNA gene complement confirms that irreversible damage of the mitochondrial DNA occurred in both mutant strains and is consistent with an essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance.
Resilience of A Learned Motor Behavior After Chronic Disruption of Inhibitory Circuits
Authors: Torok Zsofia , Luebbert Laura , Feldman Jordan , Duffy Alison , Nevue Alexander A. , Wongso Shelyn , Mello Claudio V. , Fairhall Adrienne , Pachter Lior , Gonzalez Walter G. , Lois Carlos 
Published: May 2023

AbstractMaintaining motor behaviors throughout life is crucial for an individual’s survival and reproductive success. The neuronal mechanisms that preserve behavior are poorly understood. To address this question, we focused on the zebra finch, a bird that produces a highly stereotypical song after learning it as a juvenile. Using cell-specific viral vectors, we chronically silenced inhibitory neurons in the pre-motor song nucleus called the high vocal center (HVC), which caused drastic song degradation. However, after producing severely degraded vocalizations for around 2 months, the song rapidly improved, and animals could sing songs that highly resembled the original. In adult birds, single-cell RNA sequencing of HVC revealed that silencing interneurons elevated markers for microglia and increased expression of the Major Histocompatibility Complex I (MHC I), mirroring changes observed in juveniles during song learning. Interestingly, adults could restore their songs despite lesioning the lateral magnocellular nucleus of the anterior neostriatum (LMAN), a brain nucleus crucial for juvenile song learning. This suggests that while molecular mechanisms may overlap, adults utilize different neuronal mechanisms for song recovery. Chronic and acute electrophysiological recordings within HVC and its downstream target, the robust nucleus of the archistriatum (RA), revealed that neuronal activity in the circuit permanently altered with higher spontaneous firing in RA and lower in HVC compared to control even after the song had fully recovered. Together, our findings show that a complex learned behavior can recover despite extended periods of perturbed behavior and permanently altered neuronal dynamics. These results show that loss of inhibitory tone can be compensated for by recovery mechanisms partly local to the perturbed nucleus and do not require circuits necessary for learning.
SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration
Authors: Thumu Surya Chandra Rao , Jain Monika , Soman Sumitha , Das Soumen , Verma Vijaya , Nandi Arnab , Gutmann David H. , Jayaprakash Balaji , Nair Deepak , Clement James Premdoss , Marathe Swananda , Ramanan Narendrakumar 
Published: May 2023

AbstractReactive astrogliosis is a common pathological hallmark of central nervous system (CNS) injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. TheseSrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains ofSrfknockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases,SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce β-amyloid plaques in mouse models of Parkinson’s and Alzheimer’s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.
Extending PROXIMAL to predict degradation pathways of phenolic compounds in the human gut microbiota
Authors: Balzerani Francesco , Blasco Telmo , Pérez-Burillo Sergio , Valcarcel Luis , Planes Francisco J. , Hassoun Soha 
Published: May 2023

ABSTRACTDespite significant advances in reconstructing genome-scale metabolic networks, the understanding of cellular metabolism remains incomplete for many organisms. A promising approach for elucidating cellular metabolism is analysing the full scope of enzyme promiscuity, which exploits the capacity of enzymes to bind to non-annotated substrates and generate novel reactions. To guide time-consuming costly experimentation, different computational methods have been proposed for exploring enzyme promiscuity. One relevant algorithm is PROXIMAL, which strongly relies on KEGG to define generic reaction rules and link specific molecular substructures with associated chemical transformations. Here, we present a completely new pipeline, PROXIMAL2, which overcomes the dependency on KEGG data. In addition, PROXIMAL2 introduces two relevant improvements with respect to the former version: i) correct treatment of multi-step reactions and ii) tracking of electric charges in the transformations. We compare PROXIMAL and PROXIMAL2 in recovering annotated products from substrates in KEGG reactions, finding a highly significant improvement in the level of accuracy. We then applied PROXIMAL2 to predict degradation reactions of phenolic compounds in the human gut microbiota. The results were compared to RetroPath RL, a different and relevant enzyme promiscuity method. We found a significant overlap between these two methods but also complementary results, which open new research directions into this relevant question in nutrition.
TheAzotobacter vinelandiiAlgU Regulon During Vegetative Growth and Encysting Conditions: A Proteomic Approach
Authors: Chowdhury-Paul Sangita , Martínez-Ortíz Iliana C. , Pando-Robles Victoria , Moreno Soledad , Espín Guadalupe , Merino Enrique , Núñez Cinthia 
Published: May 2023

AbstractIn thePseduomonadaceafamily, the extracytoplasmic function sigma factor AlgU is crucial to withstand adverse conditions.Azotobacter vinelandii,a closed relative ofPseudomonas aeruginosa, has been a model for cellular differentiation in Gram-negative bacteria since it forms desiccation-resistant cysts. Previous work demonstrated the essential role of AlgU to withstand oxidative stress and onA. vinelandiidifferentiation, particularly for the positive control of alginate production. In this study, the AlgU regulon was dissected by a proteomic approach under vegetative growing conditions and upon encystment induction. Our results revealed several molecular targets that explained the requirement of this sigma factor during oxidative stress and extended its role in alginate production. Furthermore, we demonstrate that AlgU was necessary to produce alkyl resorcinols, a type of aromatic lipids that conform the cell membrane of the differentiated cell. AlgU was also found to positively regulate stress resistance proteins such as OsmC, LEA-1, or proteins involved in trehalose synthesis. A position-specific scoring-matrix (PSSM) was generated based on the consensus sequence recognized by AlgU inP. aeruginosa, which allowed the identification of direct AlgU targets in theA. vinelandiigenome. This work further expands our knowledge about the function of the ECF sigma factor AlgU inA. vinelandiiand contributes to explains its key regulatory role under adverse conditions.
The mature N termini ofPlasmodiumeffector proteins confer specificity of export
Authors: Hasan Muhammad M. , Polino Alexander J. , Mukherjee Sumit , Vaupel Barbara , Goldberg Daniel E. 
Published: May 2023

AbstractThe intraerythrocytic malaria parasitePlasmodium falciparumexports hundreds of proteins into the host red blood cell (RBC). Most are targeted to the ER by a stretch of hydrophobic amino acids and cleaved further downstream at a conserved motif called the Protein Export Element (PEXEL) by the ER protease plasmepsin V (PM V). The mature effectors then travel through the secretory pathway to the parasitophorous vacuole (PV) that surrounds the parasite. There, PEXEL proteins are somehow recognized as export-destined proteins, as opposed to PV- resident proteins, and are selectively translocated out into the RBC. The mature N terminus appears to be important for export. There is conflicting data on whether PM V cleavage is needed for proper export, or whether any means of generating the mature N terminus would suffice. We replaced the PEXEL-containing N-terminal sequence of an exported GFP reporter with a signal peptide sequence and showed that precise cleavage by signal peptidase, generating the proper mature N terminus, yields export competence. Expressing a construct with only the native ER targeting signal without the PM V cleavage site dramatically decreased the amount of a mature PEXEL reporter, indicating that the hydrophobic stretch lacks an efficient cleavage signal. Therefore, the PEXEL motif functions as a specialized signal cleavage site when appropriately located after an ER targeting sequence. Our data suggest that PM V cleavage and RBC export are two independent events for PEXEL proteins. We also tested and rejected the hypothesis that an alpha-helical mature N terminus is necessary for export.ImportanceMalaria parasites export hundreds of proteins to the cytoplasm of the host red blood cells for their survival. A five amino acid sequence, called the PEXEL motif, is conserved among many exported proteins and is thought to be a signal for export. However, the motif is cleaved inside the endoplasmic reticulum of the parasite and mature proteins starting from the fourth PEXEL residue travel to the parasite periphery for export. We showed that the PEXEL motif is dispensable for export as long as identical mature proteins can be efficiently produced via alternative means in the ER. We also showed that the exported and non-exported proteins are differentiated at the parasite periphery based on their mature N termini, however, any discernible export signal within that region remained cryptic. Our study resolves a longstanding paradox in PEXEL protein trafficking.
Behavioral Consequences of Velocity Commands: Brownian Processes in Human Motor Tasks
Authors: Tessari Federico , Hermus James , Sugimoto-Dimitrova Rika , Hogan Neville 
Published: May 2023

AbstractThe motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce “random walks”, also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity.
Are circadian amplitudes and periods correlated? A newtwistin the story
Authors: Olmo Marta del , Schmal Christoph , Mizaikoff Camillo , Grabe Saskia , Gabriel Christian , Kramer Achim , Herzel Hanspeter 
Published: May 2023

AbstractThree parameters are important to characterize a circadian and in general any biological clock: period, phase and amplitude. While circadian periods have been shown to correlate with entrainment phases, and clock amplitude influences the phase response of an oscillator to pulse-like zeitgeber signals, the co-modulations of amplitude and periods, which we term twist, have not been studied in detail. In this paper we define two concepts: parametric twist refers to amplitude-period correlations arising in ensembles of self-sustained clocks in the absence of external inputs, and phase space twist refers to the co-modulation of an individual clock’s amplitude and period in response to external zeitgebers. Our findings show that twist influences the interaction of oscillators with the environment, facilitating entrainment, fastening recovery to pulse-like perturbations or modifying the response of an individual clock to coupling. This theoretical framework might be applied to understand the emerging properties of other oscillating systems.
Effects of lithium on locomotor activity and circadian rhythm of honey bees
Authors: Erdem Babur , Arslan Okan Can , Sevin Sedat , Gozen Ayse Gul , Agosto Jose L. , Giray Tugrul , Alemdar Hande 
Published: May 2023

ABSTRACTThe miticide effect of lithium on the honey bee (Apis mellifera) parasiteVarroahas been discovered.Varroamite is considered the principal threat to bee health and, as a result, to pollination and food security. In this study, we investigated the behavioral effects of lithium on honey bees, specifically locomotor activity (LMA) level and circadian patterns of LMA, such as rhythmicity, and periodicity. Any effects of lithium on activity may be important for bee health since timing and daylight are critical for bee foraging and bee’s use of the sun compass for navigation and communication. Both acute and chronic lithium treatments affected the LMA of honey bees. The effect varies depending on light and dark conditions. Chronic treatment with lithium disrupted the rhythmicity and altered the period of the circadian rhythm. While the circadian period was not affected by the light condition in the control group, lithium treatment lengthened the period in constant light condition. Lithium decreased total LMA in a constant light condition where typically activity is increased and not under the dark condition, both in acute and chronic treatments. However, mortality in the high-dose lithium treatment group is higher in the dark environment in the acute experiment. Lithium is also the first-line therapy for bipolar disorder. This disorder causes excessively elevated activity called mania and circadian rhythm abnormalities. The effects of lithium on reducing light-induced activity and the circadian rhythm of bees are reminiscent of its stabilizing effect on activity and circadian rhythms in bipolar disorder treatment.
Epigenetic reprogramming of imprinting at meiosis
Authors: Montgomery Sean A. , Berger Frédéric 
Published: May 2023

AbstractIn mammals, genomic imprinting results from different sets of epigenetic marks that distinguish the parental origins of loci in the progeny. Epigenetic reprogramming of genomic imprinting is necessary to establish a totipotent cell state. The consecutive erasure of parental epigenetic marks and the deposition of new marks occurs alongside major life stage transitions including gametogenesis and fertilization. However, despite occurring concomitantly with gametogenesis, the role of meiosis in epigenetic reprogramming has received little attention. To address this question, we use the model bryophyteMarchantia polymorpha. Following the haploid reproductive phase of this land plant, the expression of the paternal genome is silenced by the histone modification H3K27me3 in the short-lived diploid embryo. We show that imprinting is erased during meiosis, which occurs separately from gametogenesis and fertilization in Marchantia. The epigenetic reprogramming initiated during meiosis is completed in the meiotic spores where the chromatin landscape of the next haploid generation is establishedde novo. Hence, our findings illustrate a potential role for meiosis in epigenetic reprogramming that may be generalized to other sexually reproducing species.