bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conflict between short-and long-term experiences affects visual perception by modulating sensory or motor response system: evidence from Bayesian inference models
Authors: Wang Jing-Yi , Gong Xiu-Mei , Sun Qi 
Published: May 2023

AbstractHuge studies have explored the effects of short-and long-term experiences on visual perception, respectively. However, no study investigated whether and how the conflict between the two types of experiences affected our visual perception. To address this question, we adopted a task of estimating simulated self-motion directions (i.e., headings) from optic flow, in which a long-term experience – straight-forward motion is more often than lateral motion – plays an important role. The long-term experience is learned daily or encoded in our brains from birth. The heading directions in the experiment were selected from three different distributions, generating different conflicts between short-and long-term experiences. The results showed that both estimation errors and sizes of serial dependence of previously seen headings on current heading estimates varied when the experience conflict changed. Finally, we developed two Bayesian inference models, assuming that the experience conflict affected visual perception by influencing the sensory representation’s likelihood distribution or motor decision process. We found that both models captured participants’ estimation errors and serial dependences well in three distributions. In conclusion, the current study revealed the effects of the conflict between short-and long-term experiences on visual perception and preliminarily uncovered that Bayesian inference theory could explain the effects. Moreover, the study implied that the experience conflict affected visual perception by modulating our sensory or motor response systems.
Mixed-Feedback Architectures for Precise Event Timing Through Stochastic Accumulation of Biomolecules
Authors: Rezaee Sayeh , Nieto César , Singh Abhyudai 
Published: May 2023

AbstractThe timing of biochemical events is often determined by the accumulation of a protein or chemical species to a critical threshold level. In a stochastic model, we define event timing as the first-passage time for the level to cross the threshold from zero or random initial conditions. This first-passage time can be modulated by implementing feedback in synthesis, that is, making the production rate an arbitrary function of the current species level. We aim to find the optimal feedback strategy that reduces the timing noise around a given mean first-passage time. Previous results have shown that while a no-feedback strategy (i.e., an independent constant production rate) is optimal in the absence of degradation and zero-molecules initial condition, a negative feedback is optimal when the process starts at random initial conditions. We show that when the species can be degraded and the synthesis rates are set to depend linearly on the number of molecules, a positive feedback strategy (the production rate increases with the level of the molecule) minimizes timing noise. However, if no constraints on the feedback are imposed, the optimal strategy involves a mixed feedback approach, which consists of an initial positive feedback followed by a sharp negative feedback (the production rate decreases with the level) near the threshold. Finally, we quantify the fundamental limits of timing noise reduction with and without feedback control when time-keeping species are subject to degradation.
EEG resting state alpha dynamics predict individual proneness to auditory hallucinations
Authors: Honcamp H. , Duggirala S.X. , Rodino Climent J. , Astudillo A. , Trujillo-Barreto N.J. , Schwartze M. , Linden D.E.J. , van Amelsvoort T.A.M.J. , El-Deredy W. , Kotz S.A. 
Published: May 2023

AbstractIntroductionAuditory verbal hallucinations (AVH) are a transdiagnostic phenomenon but also occur in the general population. The disposition to experience AVH is considered a continuous expression from non-clinical to clinical hallucination proneness (HP). Currently, little is known about the neurophysiology of the non-clinical HP part of the continuum. AVH might result from a heightened sensitivity to sensory inputs and a decreased ability to differentiate between externally and internally generated input. Resting state (RS) alpha band activity is associated with perceptual sensitivity, attentional shifts, and cognitive control. Accordingly, spontaneous alpha fluctuations might present as a HP correlate. To investigate the time-varying dynamics of alpha band activity, we deployed a novel method for brain state allocation.MethodsWe recorded RS electroencephalography (EEG) data from 33 individuals with varying levels of HP but without clinically relevant hallucinations and used a Hidden Semi-Markov Model (HsMM) to identify five recurrent alpha states with unique temporal dynamics and topographies. The states’ mean duration and occupancy were analyzed as a function of HP. The sources of each state were reconstructed to identify the most active brain areas and their correspondence with known resting state networks.ResultsOccupancy and mean duration of a state corresponding to sensorimotor, auditory, and default-mode network (DMN) areas significantly predicted auditory and auditory-verbal HP, but not general HP. The temporal dynamics of all other states did not relate to HP.ConclusionAlpha brain state sources align with prior results on the role of the alpha in the DMN. The temporal dynamics of alpha might reflect individual differences for attentional biases to internally generated sensory events and altered auditory perceptual sensitivity. Thus, changes in the temporal brain state dynamics of RS alpha oscillations could present as a neural marker of increased vulnerability to auditory hallucinatory experiences.
Morpho-physiobiochemical dissection reveals insight into salt-induced differential responses in genetically modified Solanum melongena L. (Bt Brinjal) varieties using an indigenous hydroponic system
Authors: Hasan Md. Nahid , Hasan Md. Nazmul , Siddiqui Md. Nurealam , Arifuzzaman Md. , Hossain Mohammad Anwar , Prodhan Shamsul H. , Ashrafuzzaman Md. 
Published: May 2023

AbstractSalinity is a major abiotic constraint of crop production in many countries, including Bangladesh, where a significant amount of cultivable areas are diversely affected by rising salt concentrations. Therefore, it is of paramount importance to figure out the possible solutions to cope with this abiotic stress. So, the development of tolerant genotypes of various crop species can be the best alternative to enhance crop production as well as to improve the livelihoods of poor marginal farmers. With this in mind, the impact of different NaCl levels (50 mM, 100 mM, and 150 mM) on four different Bt Brinjal (Bacillus thuringiensis) genotypes (BARI Bt Begun-1, BARI Bt Begun-2, BARI Bt Begun-3, and BARI Bt Begun-4) was evaluated using morpho-physicochemical analyses at growth, harvesting, and postharvest stages by establishing a new indigenous cost-effective hydroponic system. Our results show that excess salt (> 100 mM) has a detrimental effect on plant growth and development and most of the traits measured across different growth stages. Based on the different measured traits, BARI Bt Begun-1 and BARI Bt Begun-2 varieties outperformed in terms of better morpho-physiological, biochemical, photosynthetic, and antioxidant capacity under salt stress when compared to BARI Bt Begun-3 and BARI Bt Begun-4. Therefore, we conclude that BARI Bt Begun-1 and BARI Bt Begun-2 are moderately tolerant varieties, while BARI Bt Begun-3 and Begun-4 were susceptible varieties to salinity stress. The identified salt-responsive contrasting varieties can serve as valuable genetic materials in comparative genomics for breeding salt-tolerant Brinjal varieties and the newly established hydroponic system could be utilized in translational research programs.
Temporal genomics help in deciphering neutral and adaptive patterns in the contemporary evolution of kelp populations
Authors: Reynes Lauric , Fouqueau Louise , Aurelle Didier , Mauger Stéphane , Destombe Christophe , Valero Myriam 
Published: May 2023

ABSTRACTThe long-term persistence of species in the face of climate change can be evaluated by examining the interplay between selection and genetic drift in the contemporary evolution of populations. In this study, we focused on spatial and temporal genetic variation in four populations of the cold-water kelpLaminaria digitatausing thousands of SNPs (ddRAD-seq). These populations were sampled from the center to the south margin in the North Atlantic at two different time points, spanning at least two generations. By conducting genome scans for local adaptation from a single time point, we successfully identified candidate loci that exhibited clinal variation, closely aligned with the latitudinal changes in temperature. This finding suggests that temperature may drive the adaptive response of kelp populations, although other factors, such as the species’ demographic history should be considered. Furthermore, we provided compelling evidence of positive selection through the examination of allele frequency changes over time, offering additional insights into the impact of genetic drift. Specifically, we detected candidate loci exhibiting temporal differentiation that surpassed the levels typically attributed to genetic drift at the south margin, confirmed through simulations. This finding was in sharp contrast with the lack of detection of outlier loci based on temporal differentiation in a population from the North Sea, exhibiting low levels of genetic diversity, that further decreased over time. These contrasting evolutionary scenarios among populations can be primarily attributed to the differential prevalence of selection relative to genetic drift. In conclusion, our study highlights the potential of temporal genomics to gain deeper insights into the contemporary evolution of marine foundation species in response to rapid environmental changes.
Is the hydrogen of the 2’-hydroxyl group of HENMT1 aSchrödinger’shydrogen?
Authors: Kaldis Philipp , Zhao Li Na 
Published: May 2023

AbstractpiRNAs are important in protecting germline integrity. 3’-terminal 2’-O-methylation is essential for piRNA maturation and to protect it from degradation. HENMT1 carries out the 2’-O-methylation, which is of key importance for piRNA stability and functionality. However, neither the structure nor the catalytic mechanism of HENMT1 have been studied. We have constructed a catalytic-competent HENMT1 complex using computational approaches, in which Mg2+is primarily coordinated by four evolutionary conserved residues, and is further auxiliary coordinated by the 3’-O and 2’-O on the 3’-terminal nucleotide of the piRNA. Our study suggests that metal has limited effects on substrate and cofactor binding but is essential for catalysis. The reaction consists of deprotonation of the 2’-OH to 2’-O and methyl transfer from SAM to the 2’-O. The methyl transfer is spontaneous and fast. Our in-depth analysis suggests that the 2’-OH may be deprotonated before entering the active site or it may be partially deprotonated at the active site by His800 and Asp859, which are in a special alignment that facilitates the proton transfer out of the active site. Furthermore, we have developed a detailed potential reaction scenario and our study indicates that HEN1 is Mg2+utilizing but is not a Mg2+dependent enzyme.
Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexylphthalate (DEHP)
Authors: Swift Luther M. , Roberts Anysja , Pressman Jenna , Guerrelli Devon , Allen Samuel , Haq Kazi T. , Reisz Julie A , D’Alessandro Angelo , Posnack Nikki Gillum 
Published: May 2023

ABSTRACTDi-2-ethylhexylphthalate (DEHP) is commonly used in the manufacturing of plastic materials, including intravenous bags, blood storage bags, and medical-grade tubing. DEHP can leach from plastic medical products, which can result in inadvertent patient exposure. DEHP concentrations were measured in red blood cell (RBC) units stored between 7-42 days (23-119 μg/mL). Using these concentrations as a guide, Langendorff-perfused rat heart preparations were acutely exposed to DEHP. Sinus activity remained stable with lower doses of DEHP (25-50 μg/mL), but sinus rate declined by 43% and sinus node recovery time prolonged by 56.5% following 30-minute exposure to 100 μg/ml DEHP. DEHP exposure also exerted a negative dromotropic response, as indicated by a 69.4% longer PR interval, 108.5% longer Wenckebach cycle length, and increased incidence of atrioventricular uncoupling. Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on atrioventricular conduction. DEHP exposure also prolonged the ventricular action potential and effective refractory period, but had no measurable effect on intracellular calcium transient duration. Follow-up studies using hiPSC-CM confirmed that DEHP slows electrical conduction in a time (15 min – 3 hours) and dose-dependent manner (10-100 μg/mL). Previous studies have suggested that phthalate toxicity is specifically attributed to metabolites of DEHP, including mono-2-ethylhexyl phthalate (MEHP). This study demonstrates that DEHP exposure also contributes to cardiac dysfunction in a dose- and time-dependent manner. Future work is warranted to investigate the impact of DEHP (and its metabolites) on human health, with special consideration for clinical procedures that employ plastic materials.
Dissecting endocytic mechanisms reveals new molecular targets to enhance sodium iodide symporter activity with clinical relevance to radioiodide therapy
Authors: Read Martin L. , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Kocbiyik Merve , Fletcher Alice , Gorvin Caroline M. , Firth George , Fruhwirth Gilbert O. , Nicola Juan P. , Jhiang Sissy , Ringel Matthew D. , Campbell Moray J. , Sunassee Kavitha , Blower Philip J. , Boelaert Kristien , Nieto Hannah R. , Smith Vicki E. , McCabe Christopher J. 
Published: May 2023

ABSTRACTThe sodium/iodide symporter (NIS) frequently shows diminished plasma membrane (PM) targeting in differentiated thyroid cancer (DTC), resulting in suboptimal radioiodide (RAI) treatment and poor prognosis. The mechanisms which govern the endocytosis of NIS away from the PM are ill-defined. Here, we challenged the hypothesis that new mechanistic understanding of NIS endocytosis would facilitate prediction of patient outcomes and enable specific drug modulation of RAI uptake in vivo. Through mutagenesis, NanoBiT interaction assays, cell surface biotinylation assays, RAI uptake and NanoBRET, we identify an acidic dipeptide within the NIS C-terminus which mediates binding to the σ2 subunit of the Adaptor Protein 2 (AP2) heterotetramer. We discovered that the FDA-approved drug chloroquine modulates NIS accumulation at the PM in a functional manner that is AP2 dependent. In vivo, chloroquine treatment of BALB/c mice significantly enhanced thyroidal uptake of99mTc pertechnetate in combination with the histone deacetylase (HDAC) inhibitor SAHA, accompanied by increased thyroidal NIS mRNA. Bioinformatic analyses validated the clinical relevance of AP2 genes with disease-free survival in RAI-treated DTC, enabling construction of an AP2 gene-related risk score classifier for predicting recurrence. We propose that NIS internalisation is orchestrated by the interaction of a C-terminal diacidic motif with AP2σ2, together with the proto-oncogene PBF acting via AP2μ2. Given that NIS internalisation was specifically druggable in vivo, our data provide new translatable potential for improving RAI therapy using FDA-approved drugs in patients with aggressive thyroid cancer.SummaryWe delineate the role of endocytic genes in regulating NIS activity at the plasma membrane and highlight the potential for systemic targeting of endocytosis to enhance radioiodine effectiveness in radioiodine-refractory cancer cells.
Pose prediction accuracy in ligand docking to RNA
Authors: Agarwal Rupesh , Rajeshwar T. Rajitha , Smith Jeremy C. 
Published: May 2023

AbstractStructure-based virtual high-throughput screening is used in early-stage drug discovery. Over the years, docking protocols and scoring functions for protein-ligand complexes have evolved to improve accuracy in the computation of binding strengths and poses. In the last decade, RNA has also emerged as a target class for new small molecule drugs. However, most ligand docking programs have been validated and tested for proteins and not RNA. Here, we test the docking power (pose prediction accuracy) of three state-of-the-art docking protocols on ∼173 RNA-small molecule crystal structures. The programs are AutoDock4 (AD4) and AutoDock Vina (Vina), which were designed for protein targets, and rDock, which was designed for both protein and nucleic acid targets. AD4 performed relatively poorly. For RNA targets for which a crystal structure of a bound ligand is available, and the goal is to identify new molecules for the same pocket, rDock performs slightly better than Vina. However, in the more common type of early-stage drug discovery setting, in which no structure of a ligand:target complex is known, rDock performed similar to Vina, with a low success rate of ∼27 %. Vina was found to bias for ligands with certain physicochemical properties whereas rDock performs similarly for all ligand properties. Thus, for projects where no ligand:protein structure already exists, Vina and rDock are both applicable. However, the relatively poor performance of all methods relative to protein target docking illustrates a need for further methods refinement.
Acute resistance exercise induces mitophagy and mitophagomes on subsarcolemmal clefts in human skeletal muscle: Focus on BNIP3L/NIX40 as a mitophagy flux marker
Authors: Díaz-Castro F. , Tuñón-Suárez M. , Quezada N. , Rivera P. , Cancino J. , Zbinden-Foncea H. , Morselli E. , Castro-Sepúlveda M. 
Published: May 2023

AbstractObjectiveMitochondrial dynamics and quality control in skeletal muscle are central to healthy metabolism. Resistance exercise is a recognized tool for improving skeletal muscle function; however, its effect on mitochondria is still not fully understood. We investigated the impact of resistance exercise on mitochondrial morphology and mitophagy in human skeletal muscle.MethodsEight healthy men performed resistance exercise on one leg, and muscle biopsies were subsequently obtained from the resting leg (Rest) and the exercised leg (Ex) to measure protein abundance and mitochondrial morphology. Additionally, muscle biopsies were obtained from twelve healthy men, and the abundance of BNIP3L protein was correlated with muscle cell and whole body health markers.ResultsEx increased p-Drp1 and decreased MFN2, Parkin, and BNIP3L protein levels. Electron microscopy indicated an increase in mitochondrial circularity, cristae abnormality, and mitophagosome structures in Ex, with a marked increase in subsarcolemmal mitophagosomes. We also identified mitophagosomes outside the muscle. Experiments in human myotubes showed a severe decrease in BNIP3L protein in response to CCCP-induced mitochondrial damage with and without bafilomycin. A positive correlation was found between BNIP3L and exercise RQ, HOMA index, while a negative correlation was found with mitophagosomes abundance and VO2max.ConclusionOur study describes the effect of resistance exercise on mitochondrial dynamics and mitophagy in skeletal muscle, demonstrating induction of mitochondrial fission and mitophagy in the exercised leg. Moreover, we propose BNIP3L as a potential regulator and marker of mitophagy flux.
ATP-Gated Potassium Channels Contribute to Ketogenic Diet-Mediated Analgesia in Mice
Authors: Enders Jonathan D. , Thomas Sarah , Lynch Paige , Jack Jarrid , Ryals Janelle M. , Puchalska Patrycja , Crawford Peter , Wright Douglas E. 
Published: May 2023

AbstractChronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (KATP) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a KATPchannel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of KATPchannels with the KATPchannel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK+cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of KATPchannels to provide ketogenic diet-related analgesia. This study also identifies KATPchannels as a new target to mimic the antinociceptive effects of a ketogenic diet.