bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarities and differences in molecular epidemiology of third-generation cephalosporin-resistant Escherichia coli carried by dogs living in urban and nearby rural settings and associated behavioural risk factors
Authors: Sealey Jordan E. , Hammond Ashley , Mounsey Oliver , Gould Virginia C. , Reyher Kristen K. , Avison Matthew B. 
Published: May 2022

SynopsisObjectivesOur aims were to compare faecal third-generation cephalosporin-resistant (3GC-R) Escherichia coli isolates from dogs living in a city and in a rural area ~30 km away; to compare isolates from dogs, cattle, and humans in these regions; to determine risk factors associated with 3GC-R E. coli carriage in these two cohorts of dogs.Methods600 dogs were included, with faecal samples processed to recover 3GC-R E. coli using 2 mg/L cefotaxime. WGS was by Illumina; risk factor analyses were multivariable linear regression using the results of an owner-completed survey.Results3GC-R E. coli were excreted by 20/303 rural and 31/297 urban dogs. Dog/human sharing was evident for the dominant canine 3GC-R sequence type, ST963(blaCMY-2). Cattle/dog sharing was evident for CTX-M-14 and CTX-M-32-producing E. coli from rural dogs, including sharing of plasmid pMOO-32, which is common on cattle farms in the area. Feeding raw meat was associated with carrying 3GC-R E. coli in rural dogs, but not in urban dogs, where swimming in rivers was a weak risk factor.ConclusionsGiven clear zoonotic potential for resistant canine E. coli, our work suggests interventions that may reduce this threat. In rural dogs, carriage of 3GC-R E. coli, particularly CTX-M producers, was phylogenetically associated with interaction with local cattle and epidemiologically associated with feeding raw meat. In urban dogs, sources of 3GC-R E. coli appear to be more varied and include environments such as rivers.
Altered basal ganglia output during self-restraint
Authors: Gu Bon-Mi , Berke Joshua D 
Published: May 2022

AbstractSuppressing actions is essential for flexible behavior. Multiple neural circuits involved in behavioral inhibition converge upon a key basal ganglia output nucleus, the substantia nigra pars reticulata (SNr). To examine how changes in basal ganglia output contribute to self-restraint, we recorded SNr neurons during a proactive behavioral inhibition task. Rats responded to Go! cues with rapid leftward or rightward movements, but also prepared to cancel one of these movement directions on trials when a Stop! cue might occur. This action restraint – visible as direction-selective slowing of reaction times – altered both rates and patterns of SNr spiking. Overall firing rate was elevated before the Go! cue, and this effect was driven by a subpopulation of direction-selective SNr neurons. In neural state space, this corresponded to a shift away from the restrained movement. SNr neurons also showed more variable inter-spike-intervals during proactive inhibition. This corresponded to more variable state-space trajectories, which may slow reaction times via reduced preparation to move. These findings open new perspectives on how basal ganglia dynamics contribute to movement preparation and cognitive control.
Identifying Proteasome 26S Subunit, ATPase (PSMC) Family Genes as the Prognostic Indicators and Therapeutic Targets in Lung Adenocarcinoma
Authors: Ullah Md. Asad , Islam Nafisa Nawal , Moin Abu Tayab , Park Su Hyun , Kim Bonglee 
Published: May 2022

AbstractThis study explored the prognostic and therapeutic potentials of multiple Proteasome 26S Subunit, ATPase (PSMC) family of genes (PSMC1-5) in lung adenocarcinoma (LUAD) diagnosis and treatment. All the PSMCs were found to be differentially expressed (upregulated) at the mRNA and protein levels in LUAD tissues. The promoter and multiple coding regions of PSMCs were reported to be differentially and distinctly methylated, which may serve in the methylation-sensitive diagnosis of LUAD patients. Multiple somatic mutations (alteration frequency: 0.6-2%) were observed along the PSMCs coding regions in LUAD tissues that could assist in the high-throughput screening of LUAD patients. A significant association between PSMCs overexpression and LUAD patients’ poor overall and relapse-free survival (p<0.05, HR:>1.3) and individual cancer stages (p<0.001) was discovered, which justifies PSMCs as the ideal targets for LUAD diagnosis. Multiple immune cells and modulators (i.e., CD274, IDO1) were found to be associated with PSMCs expression in LUAD tissues that could aid in formulating PSMC-based diagnostic measures and therapeutic interventions for LUAD. Functional enrichment analysis of neighbor genes of PSMCs in LUAD tissues revealed different genes (i.e., SLIRP, PSMA2, NUDSF3) previously known to be involved in oncogenic processes and metastasis co-expressed with PSMCs, which could also be investigated further. Overall, this study recommends that PSMCs and their transcriptional and translational products are potential candidates for LUAD diagnostic and therapeutic measure discovery. However, further laboratory research is needed to validate the findings of this experiment.
Three-Dimensional Mitochondria Reconstructions of Murine Cardiac Muscle Changes in Size Across Aging
Authors: Vue Zer , Neikirk Kit , Vang Larry , Garza-Lopez Edgar , Christensen Trace A. , Shao Jianqiang , Lam Jacob , Beasley Heather K. , Marshall Andrea G. , Crabtree Amber , Josephs B , Rodriguez Benjamin , Kirk Benjamin , Bacevac Serif , Barongan Taylor , Shao Bryanna , Stephens Dominique C. , Kabugi Kinuthia , Koh Ho-Jin , Koh Alice , Evans Chantell S. , Taylor Brittany , Reddy Anilkumar K. , Miller-Flemming Tyne , Actkins Ky’Era V. , Zaganjor Elma , Daneshgar Nastaran , Murray Sandra A. , Mobley Bret C. , Damo Steven , Gaddy Jennifer A. , Riggs Blake , Wanjalla Celestine , Kirabo Annet , McReynolds Melanie , Gomez Jose A. , Phillips Mark A. , Exil Vernat , Dai Dao-Fu , Hinton Antentor 
Published: May 2022

ABSTRACTWith sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria break down and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the 3D networks in cardiac muscle samples of male mice at aging intervals of 3 months, 1 year, and 2 years. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the 3D volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout ofMitofilin, Chchd3, Chchd6(some members of the MICOS complex), andOpa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.
Intrauterine inflammation leads to some sex and age-specific behavior and molecular differences in mice
Authors: Cristancho Ana G. , Tulina Natalia , Anton Lauren , Barila Guillermo , Elovitz Michal A. 
Published: May 2022

ABSTRACTBackgroundPrenatal inflammation is associated with long-term adverse neurobehavioral outcomes in exposed children. Sex-specific differences in behavior have been observed in anxiety and learning; however, whether these differences manifest differently by age is unknown. This study assesses possible behavioral changes from in utero inflammation as a function of age in neonatal, juvenile, and adult animals. We also tested if the observed behavioral differences correlated to neonatal sex-specific neurogenesis gene expression changes in the hippocampus to suggest a mechanism for observed behavioral differences.MethodsCD-1 timed pregnant dams were injected in utero with lipopolysaccharide (LPS, 50μg/animal) or saline at embryonic day 15 (E15). Neonatal behavioral testing was performed on postnatal day (P) 5 on male and female pups born at term using the Ultrasonic Vocalization test (USV). Juvenile and mature animals of each sex were tested in Open Field (OF) and Barnes Maze (BM) on P28 and P67 (OF), and 32-36 and 70-75 (BM). A commercially available array designed to assess the expression of genes involved in mammalian neurogenesis was utilized for profiling gene expression in the hippocampal tissue isolated from LPS and saline-exposed P7 pups.ResultsThere were no differences in stress responses measured by neonatal USV between LPS- and saline-exposed groups of either sex. In contrast, exposure to prenatal inflammation caused a male-specific increase in anxiety in mature but not juvenile animals. Juvenile LPS-exposed females had decreased movement in OF that was not present in adult animals. In addition, we observed improved memory retrieval in response to in utero LPS in the juvenile animals of both sexes. However, there was an impairment of long-term memory in adult LPS-exposed females. Finally, gene expression analyses revealed that LPS induced sex-specific changes in genes involved in hippocampal neurogenesis.ConclusionsIntrauterine exposure to inflammation has age and sex-specific effects on anxiety and learning. These differences are not apparent in the neonatal period but begin to be evident in juvenile animals and evolve in adult animals. These sex-specific differences in learning may be correlated to sex-specific disruption of the expression of genes associated with neurogenesis in the hippocampus.
Detection of local growth patterns in longitudinally imaged low-grade gliomas
Authors: Gui Chloe , Kai Jason , Khan Ali R. , Lau Jonathan C. , Megyesi Joseph F. 
Published: May 2022

AbstractBackgroundDiffuse low-grade gliomas (LGGs) are primary brain tumors with infiltrative, anisotropic growth related to surrounding white and grey matter structures. In this study, we illustrate the use of deformation-based morphometry (DBM) as a simple and objective method to study the local change in growth patterns of LGGs.MethodsAn imaging pipeline was developed involving the creation of patient-specific average templates and nonlinear registration of pre-treatment follow-up MRIs to the average template. Jacobian maps were derived and analyzed to identify areas of tissue expansion and contraction over time.ResultsOur analysis demonstrates that tissue expansion occurs primarily around the edges of the tumor, while the lesion core and areas adjacent to obstacles, such as the skull, show no significant growth. Tumors also appeared to grow faster and predominantly in areas of white matter. Regions of the brain surrounding the lesion showed slight contraction over time, likely representing compression due to mass effect of the tumor.ConclusionsWe demonstrate that DBM is a useful clinical tool to understand the long-term clinical course of an individual’s tumor and identify areas of rapid growth, which can explain the clinical signs and symptoms, predict future symptoms, and guide targeted diagnostics and therapy.HighlightsLow-grade glioma expansion occurs primarily around the edges of the tumor.Tumor cores and tissue next to obstacles show no significant growth over time.DBM provides a clinically valuable assessment of local tumor growth and activity.
The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity
Authors: Chang Wen-Sheng , Liang Wei-Kuang , Li Dong-Han , Muggleton Neil G. , Balachandran Prasad , Huang Norden E. , Juan Chi-Hung 
Published: May 2022

AbstractElectrophysiological working memory (WM) research has shown that distinct brain areas communicate through macroscopic oscillatory activities across multiple frequency bands. Such cross-frequency interactions generate nonlinear amplitude modulations (AM) in the observed signal. Traditionally, the AM of a signal is expressed as coupling strength between the signal and a pre-specified modulator at a lower frequency. Therefore, the idea of AM and coupling cannot be separately studied. This EEG study shows that the AM of parieto-occipital alpha/beta power and the coupling between frontal theta phase and parieto-occipital alpha/beta AM provide different information on WM processing. Thirty-three participants completed a color recall task with simultaneous EEG recording. The results showed that individual differences in WM precision are associated with frontal theta power enhancement and parieto-occipital alpha/beta power suppression. Furthermore, the AM of parieto-occipital alpha/beta power predicted WM precision after presenting a target-defining probe array. The phase-amplitude coupling (PAC) between frontal theta phase and parieto-occipital alpha/beta AM increased with WM load during the processing of incoming stimuli, but they did not predict the subsequent recall performance. These results indicate that the frontoparietal PAC reflects the executive control for selecting relevant WM representations, but whether the memorized information can be retrieved depends on the subsequent amplitude variation of parieto-occipital alpha/beta power. In conclusion, individuals with higher working memory precision are associated with enhanced frontal theta power and parieto-occipital alpha/beta power suppression.
Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Authors: Murphy Ryan J. , Gunasingh Gency , Haass Nikolas K. , Simpson Matthew J. 
Published: May 2022

AbstractTumours are subject to external environmental variability. However,in vitrotumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas mostin vivotumours exist in hypoxic environments. Therefore, there are clear discrepancies betweenin vitroandin vivoconditions. We explore these discrepancies by combining tools from experimental biology, mathematical modelling, and statistical uncertainty quantification. Focusing on oxygen variability to develop our framework, we reveal key biological mechanisms governing tumour spheroid growth. Growing spheroids in time-dependent conditions, we identify and quantify novel biological adaptation mechanisms, including unexpected necrotic core removal, and transient reversal of the tumour spheroid growth phases.
Functional Comparison Between Endogenous and Synthetic Notch Systems
Authors: Khamaisi Bassma , Luca Vincent C. , Blacklow Stephen C. , Sprinzak David 
Published: May 2022

AbstractThe Notch pathway converts receptor-ligand interactions at the cell surface into a transcriptional response in the receiver cell. In recent years, synthetic Notch systems (SynNotch) that respond to different inputs and transduce different transcriptional responses have been engineered. One class of synNotch systems uses antibody-antigen interactions at the cell surface to induce the proteolytic cleavage cascade of the endogenous Notch autoregulatory core and the consequent release of a synNotch intracellular domain (ICD), converting surface antigen detection into a cellular response. However, whereas the activation of endogenous Notch requires ubiquitylation and subsequent endocytosis of the ligand ICD, these synNotch systems do not seem to have such a requirement because the synNotch ligands completely lack an ICD. This observation raises questions about existing models for the Notch activation mechanism. Here, we test how different structural and biochemical factors affect the dependence of endogenous and synthetic Notch activation on ligand ICD. We compare the behavior of antibody-antigen synNotch (aa-synNotch) to that of endogenous Notch, and to a synNotch system that uses induced FKBP-FRB dimerization with rapamycin (ff-synNotch), which still requires a ligand ICD. We found that differences in receptor-ligand affinity, in the identity of the transmembrane domain, or in the presence or absence of extracellular EGF repeats cannot explain the differences in ligand ICD requirement that distinguishes aa-synNotch from endogenous Notch or ff-synNotch. These findings suggest that the aa-SynNotch systems bypass the ligand ICD requirement because antigen-antibody pairs are able to promote other adhesive cell-cell interactions that provide the mechanical tension needed for ligand activation.
GNL3 is an evolutionarily-conserved stem cell gene influencing cell proliferation, animal growth, and regeneration in the hydrozoan Hydractinia
Authors: Quiroga-Artigas Gonzalo , de Jong Danielle , Schnitzler Christine E. 
Published: May 2022

AbstractNucleostemin (NS) is a vertebrate gene preferentially expressed in stem and cancer cells, which acts to regulate cell cycle progression, genome stability, and ribosome biogenesis. NS and its paralogous gene, GNL3-like (GNL3L), arose in the vertebrate clade after a duplication event from their orthologous gene, G protein Nucleolar 3 (GNL3). Research on invertebrate GNL3, however, has been limited. To gain a greater understanding of the evolution and functions of the GNL3 gene, we have performed studies in the hydrozoan cnidarian Hydractinia symbiolongicarpus, a colonial hydroid that continuously generates pluripotent stem cells throughout its life cycle and presents impressive regenerative abilities. We show that Hydractinia GNL3 is expressed in stem and germline cells. The knockdown of GNL3 reduces the number of mitotic and S-phase cells in Hydractinia larvae of different ages. Genome editing of Hydractinia GNL3 via CRISPR/Cas9 resulted in colonies with reduced growth rates, polyps with impaired regeneration capabilities, gonadal morphological defects, and low sperm motility. Collectively, our study shows that GNL3 is an evolutionarily-conserved stem cell and germline marker involved in cell proliferation, animal growth, regeneration, and sexual reproduction in Hydractinia, and sheds new light into the evolution of GNL3 and of stem cell systems.
Decoding reward–curiosity conflict in decision-making from irrational behaviors
Authors: Konaka Yuki , Naoki Honda 
Published: May 2022

AbstractHumans and animals are not always rational. They not only rationally exploit rewards but also explore an environment, even if reward is less expected, owing to their curiosity. However, the mechanism of such curiosity-driven irrational behavior is largely unknown. Here, we developed a novel decision-making model for a two-choice task based on the free energy principle, which is a theory integrating recognition and action selection. The model successfully described irrational behaviors depending on the curiosity level. We then proposed a machine learning method to decode temporal curiosity from behavioral data, which enables us to quantitatively compare estimated curiosity and neural activities. By applying it to rat behavioral data, we found that the irrational choices sticking to one option was reflected to the negative curiosity level. Our decoding approach can be a fundamental tool for identifying the neural basis for reward-curiosity conflicts. Specifically, it could be effective in diagnosing mental disorders.
Homogeneous inhibition is optimal for the phase precession of place cells in the CA1 field
Authors: Vandyshev G.K. , Mysin I.E. 
Published: May 2022

AbstractPlace cells are hippocampal neurons encoding the position of an animal in space. Studies of place cells are essential to understanding the processing and transmission of information by neural networks of the brain. An important characteristic of place cell spike trains is phase precession. When an animal is running through the place field, the discharges of the place cells shift from the ascending phase of the theta rhythm through the minimum to the descending phase. The role of excitatory inputs to CA1 pyramidal neurons along the Schaffer collaterals and the perforant pathway in phase precession is described, but the role of inputs from local interneurons to CA1 pyramidal cell is poorly understood. We have set the goal the contribution of field CA1 interneurons to the phase precession of place cells using mathematical methods. The CA1 field was chosen because it provides the largest set of experimental data required to build and verify the model. We have solved the optimization problem and found the parameters of the excitatory and inhibitory inputs to the pyramidal neuron of the CA1 field so that the neuron generates a spike train with the effect of phase precession. We have discovered that the uniform inhibition of field CA1 pyramidal neurons best explains the effect of phase precession. Among interneurons, axo-axonal neurons make the greatest contribution to the inhibition of pyramidal cells.
Portable low-cost macroscopic mapping system for all-optical cardiac electrophysiology
Authors: Heinson Yuli W. , Han Julie L. , Entcheva Emilia 
Published: May 2022

AbstractSignificanceAll-optical cardiac electrophysiology enables the visualization and control of key parameters relevant to the detection of cardiac arrhythmias. Mapping such responses in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) is of great interest for cardiotoxicity and personalized medicine applications.AimWe introduce and validate a very low-cost compact mapping system for macroscopic all-optical electrophysiology in layers of hiPSC-CMs.ApproachThe system uses oblique trans-illumination, low-cost cameras, light-emitting diodes and off-the-shelf components (total < $15,000) to capture voltage, calcium and mechanical waves under electrical or optical stimulation.ResultsOur results corroborate the equivalency of electrical and optogenetic stimulation of hiPSC-CMs, and Vm – [Ca2+]i similarity in conduction under pacing. Green-excitable optical sensors are combinable with blue optogenetic actuators (Chanelrhodopsin2) only under very low green light (< 0.05mW/mm2). Measurements in warmer culture medium yield larger spread of action potential duration and higher conduction velocities compared to Tyrode’s solution at room temperature.ConclusionsAs multiple optical sensors and actuators are combined, our results can help handle the “spectral congestion” and avoid parameter distortion. We illustrate the utility of the system for uncovering the action of cellular uncoupling agents and show extensibility to an epi-illumination mode for future imaging of thicker native or engineered tissues.