bluuebunny/crossref_metadata_2025_split huggingface dataset:
Worth the work? Monkeys discount rewards by a subjective adapting effort cost
Authors: Burrell Mark , Pastor-Bernier Alexandre , Schultz Wolfram 
Published: January 2023

AbstractAll life must solve how to allocate limited energy resources to maximise benefits from scarce opportunities. Economic theory posits decision makers optimise choice by maximising the subjective benefit (utility) of reward minus the subjective cost (disutility) of the required effort. While successful in many settings, this model does not fully account for how experience can alter reward-effort trade-offs. Here we test how well the subtractive model of effort disutility explains the behavior of two non-human primates (Macaca mulatta) in a binary choice task in which reward quantity and physical effort to obtain were varied.Applying random utility modelling to independently estimate reward utility and effort disutility, we show the subtractive effort model better explains out-of-sample choice behavior when compared to parabolic and exponential effort discounting. Furthermore, we demonstrate that effort disutility is dependent on previous experience of effort: in analogy to work from behavioral labour economics, we develop a model of reference-dependent effort disutility to explain the increased willingness to expend effort following previous experience of effortful options in a session. The result of this analysis suggests that monkeys discount reward by an effort cost that is measured relative to an expected effort learned from previous trials. When this subjective cost of effort, a function of context and experience, is accounted for, trial-by-trial choice behavior can be explained by the subtractive cost model of effort.Therefore, in searching for net utility signals that may underpin effort-based decision-making in the brain, careful measurement of subjective effort costs is an essential first step.SignificanceAll decision-makers need to consider how much effort they need to expend when evaluating potential options. Economic theories suggest that the optimal way to choose is by cost-benefit analysis of reward against effort. To be able to do this efficiently over many decision contexts, this needs to be done flexibly, with appropriate adaptation to context and experience. Therefore, in aiming to understand how this might be achieved in the brain, it is important to first carefully measure the subjective cost of effort. Here we show monkeys make reward-effort cost-benefit decisions, subtracting the subjective cost of effort from the subjective value of rewards. Moreover, the subjective cost of effort is dependent on the monkeys’ experience of effort in previous trials.
Immobilisation of Lipophilic and Amphiphilic Biomarker on Hydrophobic Microbeads
Authors: Dinter Franziska , Thiehle Thomas , Schedler Uwe , Lehmann Werner , Schierack Peter , Rödiger Stefan 
Published: January 2023

AbstractBackgroundLipids and amphiphilic molecules are ubiquitous and play a central role in cell signalling, cell membrane structure, and lipid transport in the human body. However, they also appear in many diseases such as atherosclerosis, cardiovascular diseases, infections, inflammatory diseases, cancer, and autoimmune diseases. Thus, it is necessary to have detection systems for lipids and amphiphilic molecules. Microbeads can be one of these systems for the simultaneous detection of different lipophilic biomarkers.MethodsBased on the fundamentals of microbead development, novel hydrophobic microbeads were produced. These not only have a hydrophobic surface, but are also fluorescently encoded and organic solvent resistant. The challenge after the development of the hydrophobic microbeads was to immobilise the amphiphilic molecules, in this study phospholipids, on the microbead surface in an oriented direction. After successful immobilisation of the biomarkers, a suitable antibody based detection assay was established.ResultsBy passive adsorption, the phospholipids cardiolipin, phosphatidylethanolamine and phosphatidylcholine could be bound to the microbead surface. With the application of the enzymes phospholipase A2 and phospholipase C, the directional binding of the phospholipids to the microbead surface was demonstrated. The detection of directional binding indicated the need for the hydrophobic surface. Microbeads with no hydrophobic surface bound the phospholipids non-directionally (with the hydrophilic head) and were thus no longer reactively accessible for detection.ConclusionWith the newly developed hydrophobic, dual coded and solvent stable microbeads it is possible to bind amphiphilic biomolecules directionally onto the microbead surfaces.
Developmental hearing loss-induced perceptual deficits are rescued by cortical expression of GABABreceptors
Authors: Masri Samer , Fair Regan , Mowery Todd M. , Sanes Dan H. 
Published: January 2023

AbstractEven transient periods of developmental hearing loss during the developmental critical period have been linked to long-lasting deficits in auditory perception, including temporal and spectral processing, which correlate with speech perception and educational attainment. In gerbils, hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAAand metabotropic GABABreceptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAAreceptors. We developed viral vectors to express both endogenous GABAAor GABABreceptor subunits in auditory cortex and tested their capacity to restore perception of temporal and spectral auditory cues following critical period hearing loss in the Mongolian gerbil. HL significantly impaired perception of both temporal and spectral auditory cues. While both vectors similarly increased IPSCs in auditory cortex, only overexpression of GABABreceptors improved perceptual thresholds after HL to be similar to those of animals without developmental hearing loss. These findings identify the GABABreceptor as an important regulator of sensory perception in cortex and point to potential therapeutic targets for developmental sensory disorders.Significance StatementHearing loss in children can induce deficits in aural communication that persevere even after audibility has returned to normal, suggesting permanent changes to the auditory central nervous system. In fact, a reduction in cortical synaptic inhibition has been implicated in a broad range of developmental disorders, including hearing loss. Here, we tested the hypothesis that developmental hearing loss-induced perceptual impairments in gerbils are caused by a permanent reduction of auditory cortical inhibitory synapse strength. We found that virally-mediated expression of a GABABreceptor subunit in gerbil auditory cortex was able to restore two auditory perceptual skills in juvenile animals reared with hearing loss, suggesting that cortical synaptic inhibition is a plausible therapeutic target for sensory processing disorders.
Deconfounded Dimension Reduction via Partial Embeddings
Authors: Chen Andrew A. , Clark Kelly , Dewey Blake , DuVal Anna , Pellegrini Nicole , Nair Govind , Jalkh Youmna , Khalil Samar , Zurawski Jon , Calabresi Peter , Reich Daniel , Bakshi Rohit , Shou Haochang , Shinohara Russell T. ,   the Alzheimer’s Disease Neuroimaging Initiative,   the North American Imaging in Multiple Sclerosis Cooperative
Published: January 2023

AbstractDimension reduction tools preserving similarity and graph structure such ast-SNE and UMAP can capture complex biological patterns in high-dimensional data. However, these tools typically are not designed to separate effects of interest from unwanted effects due to confounders. We introduce the partial embedding (PARE) framework, which enables removal of confounders from any distance-based dimension reduction method. We then develop partialt-SNE and partial UMAP and apply these methods to genomic and neuroimaging data. Our results show that the PARE framework can remove batch effects in single-cell sequencing data as well as separate clinical and technical variability in neuroimaging measures. We demonstrate that the PARE framework extends dimension reduction methods to highlight biological patterns of interest while effectively removing confounding effects.
Updated phylogeny and protein structure predictions revise the hypothesis on the origin of MADS-box transcription factors in land plants
Authors: Qiu Yichun , Li Zhen , Walther Dirk , Köhler Claudia 
Published: January 2023

AbstractMADS-box transcription factors (TFs) are broadly present in eukaryotes. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). For about twenty years, Type I and II genes were considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs got lost in the MRCA of Archaeplastida (the kingdom Plantaesensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type upon the evolution of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs largely expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. We attribute the adaptation to the terrestrial environment partly to the divergence among MEF2-type MADS-box genes and the repetitive recruitment of these originally stress-responsive TFs into developmental programs, especially those underlying reproduction.
Characterization and Applications of Evoked Responses During Epidural Electrical Stimulation
Authors: Verma Nishant , Romanauski Ben , Lam Danny , Lujan Luis , Blanz Stephan , Ludwig Kip , Lempka Scott , Knudson Bruce , Nishiyama Yuichiro , Hao Jian , Park Hyun-Joo , Ross Erika , Lavrov Igor , Zhang Mingming 
Published: January 2023

AbstractEpidural electrical stimulation (EES) of the spinal cord has been FDA approved and used therapeutically for decades. However, there is still not a clear understanding of the local neural substrates and consequently the mechanism of action responsible for the therapeutic effects. Epidural spinal recordings (ESR) are collected from the electrodes placed in the epidural space. ESR contains multi-modality signal components such as the evoked neural response (due to tonic or BurstDR™waveforms), evoked muscle response, stimulation artifact, and cardiac response. The tonic stimulation evoked compound action potential (ECAP) is one of the components in ESR and has been proposed recently to measure local neural activation during EES. Here, we first review and investigate the referencing strategies, as they apply to ECAP component in ESR in the domestic swine animal model. We then examine how ECAP component can be used to sense lead migration, an adverse outcome following lead placement that can reduce therapeutic efficacy. Lastly, we show and isolate concurrent activation of local back and leg muscles during EES, demonstrating that the ESR obtained from the recording contacts contain both ECAP and EMG components. These findings may further guide the implementation of recording and reference contacts in an implantable EES system and provide preliminary evidence for the utility of ECAP component in ESR to detect lead migration. We expect these results to facilitate future development of EES methodology and implementation of use of different components in ESR to improve EES therapy.
The MOM1 complex recruits the RdDM machinery via MORC6 to establishde novoDNA methylation
Authors: Li Zheng , Wang Ming , Zhong Zhenhui , Gallego-Bartolomé Javier , Feng Suhua , Jami-Alahmadi Yasaman , Wang Xinyi , Wohlschlegel James , Bischof Sylvain , Long Jeffrey A. , Jacobsen Steven E. 
Published: January 2023

AbstractMOM1 is anArabidopsisfactor previously shown to mediate transcriptional silencing independent of major DNA methylation changes. Here we found that MOM1 localizes with sites of RNA-directed DNA methylation (RdDM). Tethering MOM1 with artificial zinc finger to unmethylatedFWApromoter led to establishment of DNA methylation andFWAsilencing. This process was blocked by mutations in components of the Pol V arm of the RdDM machinery, as well as by mutation ofMORC6. We found that at some endogenous RdDM sites, MOM1 is required to maintain DNA methylation and a closed chromatin state. In addition, efficient silencing of newly introducedFWAtransgenes was impaired by mutation of MOM1 or mutation of genes encoding the MOM1 interacting PIAL1/2 proteins. In addition to RdDM sites, we identified a group of MOM1 peaks at active chromatin near genes that colocalized with MORC6. These findings demonstrate a multifaceted role of MOM1 in genome regulation.
eIF2B localisation and its regulation during the integrated stress response is cell type specific
Authors: Hanson Filipe M. , Ribeiro de Oliveira Madalena I. , Cross Alison K. , Allen K. Elizabeth , Campbell Susan G. 
Published: January 2023

AbstractEukaryotic initiation factor 2B (eIF2B) is a master regulator of translation control. eIF2B recycles inactive eIF2-GDP to active eIF2-GTP. Under transient/acute cellular stress, a family of kinases phosphorylate the alpha subunit of eIF2 (eIF2α-P[S51]) activating the integrated stress response (ISR). This response pathway inhibits eIF2B activity resulting in overall translation attenuation and reprogramming of gene expression to overcome the stress. The duration of an ISR programme can dictate cell fate wherein chronic activation has pathological outcomes. Vanishing white matter disease (VWMD) is a chronic ISR-related disorder linked to mutations in eIF2B. eIF2B is vital to all cell types, yet VWMD eIF2B mutations primarily affect astrocytes and oligodendrocytes suggesting cell type-specific functions of eIF2B. Regulation of the cytoplasmic localisation of eIF2B (eIF2B bodies) has been implicated in the ISR. Here, we highlight the cell type specific localisation of eIF2B within neuronal and glial cell types. Our analyses revealed that each cell type possesses its own steady-state repertoire of eIF2B bodies with varied subunit composition and activity. We also demonstrate that neural and glial cell types respond similarly to acute induction of the ISR whilst a chronic ISR programme exerts cell type-specific differences. Regulatory composition of eIF2B bodies is suggested to be differentially modulated in a manner that correlates to the action of acute and chronic ISR. We also highlight a cell type specific response of the ISR inhibitor ISRIB on eIF2B localisation and activity.
On the physiological and structural contributors to the overall balance of excitation and inhibition in local cortical networks
Authors: Shirani Farshad , Choi Hannah 
Published: January 2023

AbstractOverall balance of excitation and inhibition in cortical networks is central to their functionality and normal operation. Such orchestrated co-evolution of excitation and inhibition is established through convoluted local interactions between neurons, which are organized by specific network connectivity structures and are dynamically controlled by modulating synaptic activities. Therefore, identifying how such structural and physiological factors contribute to establishment of overall balance of excitation and inhibition is crucial in understanding the homeostatic plasticity mechanisms that regulate the balance. We use biologically plausible mathematical models to extensively study the effects of multiple key factors on overall balance of a network. We characterize a network’s baseline balanced state by certain functional properties, and demonstrate how variations in physiological and structural parameters of the network deviate this balance and, in particular, result in transitions in spontaneous activity of the network to high-amplitude slow oscillatory regimes. We show that deviations from the reference balanced state can be continuously quantified by measuring the ratio of mean excitatory to mean inhibitory synaptic conductances in the network. Our results suggest that the commonly observed ratio of the number of inhibitory to the number of excitatory neurons in local cortical networks is almost optimal for their stability and excitability. Moreover, the values of inhibitory synaptic decay time constants and density of inhibitory-to-inhibitory network connectivity are critical to overall balance and stability of cortical networks. However, network stability in our results is sufficiently robust against modulations of synaptic quantal conductances, as required by their role in learning and memory.SummaryWe leverage computational tractability of a biologically plausible conductance-based meanfield model to perform a comprehensive bifurcation and sensitivity analysis that demonstrates how variations in key synaptic and structural parameters of a local cortical network affect network’s stability and overall excitation-inhibition balance. Our results reveal optimality and criticality of baseline biological values for several of these parameters, and provide predictions on their effects on network’s dynamics which can inform identifying pathological conditions and guide future experiments.
Human-specific features and developmental dynamics of the brain N-glycome
Authors: Klarić Thomas S. , Gudelj Ivan , Santpere Gabriel , Sousa André M. M. , Novokmet Mislav , Vučković Frano , Ma Shaojie , Bečeheli Ivona , Sherwood Chet C. , Ely John J. , Hof Patrick R. , Josić Djuro , Lauc Gordan , Sestan Nenad 
Published: January 2023

AbstractComparative “omics” studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. Here, we performed multi-regional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry, then integrated these data with complementary glycotranscriptomic data. We found that in primates the brain N-glycome has evolved more rapidly than the underlying transcriptomic framework, providing a mechanism for generating additional diversity. We show that brain N-glycome evolution in hominids has been characterized by an increase in complexity and α(2-6)-linked N-acetylneuraminic acid along with human-specific cell-type expression of key glycogenes. Finally, by comparing the prenatal and adult human brain N-glycome, we identify region-specific neurodevelopmental pathways that lead to distinct spatial N-glycosylation profiles in the mature brain.One-Sentence SummaryEvolution of the human brain N-glycome has been marked by an increase in complexity and a shift in sialic acid linkage.
Evolutionary history ofCastanea sativaMill. in the Caucasus driven by Middle and Late Pleistocene paleoenvironmental changes
Authors: Beridze Berika , Sękiewicz Katarzyna , Walas Łukasz , Thomas Peter A. , Danelia Irina , Kvartskhava Giorgi , Fazaliyev Vahid , Bruch Angela A. , Dering Monika 
Published: January 2023

AbstractDue to global climate cooling and aridification since the Paleogene, the members of the Neogene flora were extirpated from the Northern Hemisphere or were confined to a few refugial areas. For some species, the final reduction/extinction came in the Pleistocene, but some others have survived climatic transformations up to the present. This has occurred inCastanea sativa, a species of high commercial value in Europe and a significant component of the Caucasian forests’ biodiversity. In contrast to the European range, neither the historical biogeography nor the population genetic structure of the species in the isolated Caucasian range has been clarified. Here, based on a survey of 21 natural populations from the Caucasus and a single one from Europe, we provide likely biogeographic reconstruction and genetic diversity details. By applying Bayesian inference, species distribution modelling, and fossil pollen data, we estimated (1) the time of the Caucasian - European divergence during the Middle Pleistocene (436.5 ka), (2) the time of divergence among Caucasian lineages, and (3) outlined the glacial refugia for species. The climate changes related to the Early Middle Pleistocene Transition and the alpine orogenic uplift in the region are proposed as the major drivers of the intraspecific divergence and European-Caucasian disjunction, while the impact of the last glacial cycle was of marginal importance.
Analyzing the effects of actions followed by the Central Bank of Jordan during COVID-19 pandemic on financial performance of Jordanian banks
Authors: Mugableh Mohamed Ibrahim , Malkawi Eyad Mohammad , Hammouri Mohamed Adnan 
Published: January 2023

PurposeThis study analyzes the impact of the procedures followed by the Central Bank of Jordan during the COVID-19 pandemic on the financial performance of Jordanian banks listed on the Amman Stock Exchange over the period (2019Q1–2021Q3).Design/methodology/approachThe panel fixed effect model was used to measure the impact of each of the required reserve ratios and the deferred loans on the profitability of Jordanian banks represented by the return on total assets.FindingsThe results revealed a negative relationship at the significance level of 10% between the required reserve ratio and the return on total assets. Also, there is a negative relationship at the significance level of 5% between the deferred loans and the return on total assets.Research limitations/implicationsThe paper recommends the Central Bank of Jordan following a precautionary policy to encounter systematic risks that cannot be eliminated by using diversification.Originality/valueWith the severe impact of the Coronavirus pandemic on the overall economic performance of the national economic sectors and the subsequent negative impact on the living standard of society’s members, this study shows the government’s role represented by the procedures of its monetary authority (Central Bank of Jordan) to mitigate the effects of this pandemic, as well as measuring the impact of these procedures on the financial performance of Jordanian banks listed on the Amman Stock Exchange.