bluuebunny/crossref_metadata_2025_split huggingface dataset:
P53 Acetylation Exerts Critical Roles In Pressure Overload Induced Coronary Microvascular Dysfunction and Heart Failure
Authors: He Xiaochen , Cantrell Aubrey C , Williams Quinesha A , Gu Wei , Chen Yingjie , Chen Jian-Xiong , Zeng Heng 
Published: February 2023

AbstractCoronary microvascular dysfunction (CMD) has been shown to contribute to cardiac hypertrophy and heart failure with preserved ejection fraction. At this point, there are no proven treatments for CMD. We have shown that histone acetylation may play a critical role in the regulation of CMD. By using a mouse model that replaces lysine with arginine at residues K98/117/161/162R of p53 (p534KR), preventing acetylation at these sites, we test the hypothesis that acetylation-deficient p534KRcould improve coronary microvascular dysfunction and prevent the progression of hypertensive cardiac hypertrophy and heart failure. Wild-type (WT) and p534KRmice were subjected to pressure overload (PO) by transverse aortic constriction to induce cardiac hypertrophy and heart failure (HF). Echocardiography measurements revealed improved cardiac function together with reduction of apoptosis and fibrosis in p534KRmice. Importantly, myocardial capillary density and coronary flow reserve (CFR) were significantly improved in p534KRmice. Moreover, p534KRupregulated the expression of cardiac glycolytic enzymes and glucose transporters, as well as the level of fructose-2,6-biphosphate; increased PFK-1 activity; and attenuated cardiac hypertrophy. These changes were accompanied by increased expression of HIF-1α and proangiogenic growth factors. Additionally, the levels of SERCA-2 were significantly upregulated in sham p534KRmice as well as in p534KRmice after TAC.In vitro, p534KRsignificantly improved endothelial cell (EC) glycolytic function and mitochondrial respiration, and enhanced EC proliferation and angiogenesis. Similarly, acetylation-deficient p534KRsignificantly improved CFR and rescued cardiac dysfunction in SIRT3 KO mice. Our data reveal the importance of p53 acetylation in coronary microvascular function, cardiac function, and remodeling, and may provide a promising approach to improve hypertension-induced coronary microvascular dysfunction (CMD) and to prevent the transition of cardiac hypertrophy to heart failure.
WITHDRAWN: Enhancing Mutational Hotspot Predictions: The Role of Atomic Fluctuations
Authors: Martis Elvis A. F. , Coutinho Evans C. 
Published: February 2023

Withdrawal StatementThe authors have withdrawn this manuscript because the reviewers have suggested significant revision of the manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Rice plants alter their yield component parameters based on their tolerance to low temperatures determined by a non-invasive method during the vegetative stage
Authors: Carolina Michelini María , Gazquez Ayelén , Checovich Mariana Leonela , Maiale Santiago Javier , Menéndez Ana Bernardina , Rodríguez Andrés Alberto 
Published: February 2023

AbstractThe first rice phenological stages are commonly subjected to low temperatures (LT) in temperate crop areas. Here, plants of rice genotypes were analyzed according to their LT tolerance at seedling stage, using a realistic experimental temperatures range, and measuring quantitative and operator-independent parameters, fast-obtainable by non-invasive techniques. The ratios between values of these parameters determined in plants under LT condition with respect to the control condition were statistically analyzed. We have found a discriminant formula based on two parameters that allowed to differentiate between genotypes previously described as tolerant and sensitive to LT, with a very low general classification error. The application of the discriminant formula to score plants under LT, using all genotypes from the Rice Diversity Panel 1 which comprehensively represents the genetic variability of theO. sativaspecies, resulted in LT tolerance levels of its subspecies and subpopulations consistent with previous reports. In turn, a strong association between the LT tolerance score at the seedling stage and the panicle weight in plants under field LT during the vegetative stage, suggested that this scoring could be used as an indirect selection factor of genotypes with good yield traits and suited to LT prone environments.
A Non-Canonical IRAK Signaling Pathway Triggered by DNA Damage
Authors: Li Yuanyuan , Shah Richa B. , Sarti Samanta , Belcher Alicia L. , Lee Brian J. , Gorbatenko Andrej , Nemati Francesca , Yu Ian , Stanley Zoe , Shao Zhengping , Silva Jose M. , Zha Shan , Sidi Samuel 
Published: February 2023

AbstractInterleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptor (TLR) and IL-1R signaling, with no reported roles outside of innate immunity. We find that vertebrate cells exposed to ionizing radiation (IR) sequentially activate IRAK4 and IRAK1 through a phosphorylation cascade mirroring that induced by TLR/IL-1R, resulting in a potent anti-apoptotic response. However, IR-induced IRAK1 activation does not require the receptors or the IRAK4/1 adaptor protein MyD88, and instead of remaining in the cytoplasm, the activated kinase is immediately transported to the nucleus via a conserved nuclear localization signal. We identify: double-strand DNA breaks (DSBs) as the biologic trigger for this pathway; the E3 ubiquitin ligase Pellino1 as the scaffold enabling IRAK4/1 activation in place of TLR/IL-1R-MyD88; and the pro-apoptotic PIDDosome (PIDD1-RAIDD-caspase-2) as a critical downstream target in the nucleus. The data delineate a non-canonical IRAK signaling pathway derived from, or ancestral to, TLR signaling. This DSB detection pathway, which is also activated by genotoxic chemotherapies, provides multiple actionable targets for overcoming tumor resistance to mainstay cancer treatments.
Maturation of Nucleus Accumbens Synaptic Transmission Signals a Critical Period for the Rescue of Social Deficits in a Mouse Model of Autism Spectrum Disorder
Authors: Matthiesen Melina , Khlaifia Abdessattar , Steininger Carl Frank David , Dadabhoy Maryam , Mumtaz Unza , Arruda-Carvalho Maithe 
Published: February 2023

AbstractSocial behavior emerges early in development, a time marked by the onset of neurodevelopmental disorders featuring social deficits, including autism spectrum disorder (ASD). Although deficits in social interaction and communication are at the core of the clinical diagnosis of ASD, very little is known about their neural correlates at the time of clinical onset of the disorder. The nucleus accumbens (NAc), a brain region extensively implicated in social behavior, undergoes synaptic, cellular and molecular alterations in early life, and is particularly affected in ASD mouse models. To explore a link between the maturation of the NAc and neurodevelopmental deficits in social behavior, we compared age-dependent changes in spontaneous synaptic transmission in NAc shell medium spiny neurons (MSNs) between the highly social C57BL/6J mouse strain and the idiopathic ASD mouse model BTBRT+Itpr3tf/Jat postnatal day (P) 4, P6, P8, P12, P15, P21 and P30. We found that MSNs from both C57BL/6J and BTBR mice display age-dependent increases in spontaneous excitatory and inhibitory synaptic currents between P4 and P30. Comparison of NAc spontaneous transmission between strains showed that BTBR MSNs display increased excitatory transmission during the first postnatal week, and increased inhibition across the first, second and fourth postnatal weeks, suggesting accelerated maturation of excitatory and inhibitory synaptic inputs onto BTBR MSNs compared to C57BL/6J mice. These early life changes in synaptic transmission are consistent with a potential critical period in the maturation of the NAc, which could maximize the efficacy of interventions affecting social behavior. To test this possibility, we treated BTBR mice in either early life (P4-P8) or adulthood (P60-P64) with the mTORC1 antagonist rapamycin, a well-established rescue intervention for ASD-like behavior. We found that rapamycin treatment rescued social interaction deficits in BTBR mice when injected in infancy, but not in adulthood. These data emphasize the importance of studying brain regions involved in the pathophysiology of neurodevelopmental disorders at clinically-relevant time points, which may offer novel insight into the timing and targets of therapeutic interventions to maximize positive outcomes.
Hippocampal mechanisms support cortisol-induced memory enhancements
Authors: Sherman Brynn E. , Harris Bailey B. , Turk-Browne Nicholas B. , Sinha Rajita , Goldfarb Elizabeth V. 
Published: February 2023

AbstractStress can powerfully influence episodic memory, often enhancing memory encoding for emotionally salient information. These stress-induced memory enhancements stand at odds with demonstrations that stress and the stress-related hormone cortisol can negatively affect the hippocampus, a brain region important for episodic memory encoding. To resolve this apparent conflict and determine whether and how the hippocampus supports memory encoding under cortisol, we combined behavioral assays of associative memory, high-resolution functional magnetic resonance imaging (fMRI), and pharmacological manipulation of cortisol in a within-participant, double-blinded procedure. Hydrocortisone led to enhanced functional connectivity between hippocampal subregions, which predicted subsequent memory enhancements for emotional information. Cortisol also modified the relationship between hippocampal representations and memory: whereas hippocampal signatures of distinctiveness predicted memory under placebo, relative integration predicted memory under cortisol. Together, these data provide novel evidence that the human hippocampus contains the necessary machinery to support emotional memory enhancements under stress.
Fast And Accurate Population Level Transcranial Magnetic Stimulation via Low-Rank Probabilistic Matrix Decomposition (PMD)
Authors: Hasan Nahian I. , Wang Dezhi , Gomez Luis J. 
Published: February 2023

ABSTRACTTranscranial magnetic stimulation (TMS) is used to study brain function and treat mental health disorders. During TMS, a coil placed on the scalp induces an E-field in the brain that modulates its activity. TMS is known to stimulate regions that are exposed to a large E-field. Clinical TMS protocols prescribe a coil placement based on scalp landmarks. There are inter-individual variations in brain anatomy that result in variations in the TMS-induced E-field at the targeted region and its outcome. These variations across individuals could in principle be minimized by developing a large database of head subjects and determining scalp landmarks that maximize E-field at the targeted brain region while minimizing its variation using computational methods. However, this approach requires repeated execution of a computational method to determine the E-field induced in the brain for a large number of subjects and coil placements. We developed a probabilistic matrix decomposition-based approach for rapidly evaluating the E-field induced during TMS for a large number of coil placements. Our approach can determine the E-field induced in over 1 Million coil placements in 9.5 hours, in contrast, to over 5 years using a bruteforce approach. After the initial set-up stage, the E-field can be predicted over the whole brain within 2-3 milliseconds and to 2% accuracy. We tested our approach in over 200 subjects and achieved an error of < 2% in most and < 3.5% in all subjects. We will present several examples of bench-marking analysis for our tool in terms of accuracy and speed across and its applicability for population level optimization of coil placement.Graphical AbstractHighlightsA method for practical E-field informed population-level TMS coil placement strategies is developed.This algorithm enables the determination of E-field informed optimal coil placement in seconds enabling it’s use for close-loop and on-the-fly reconfiguration of TMS.After the initial set-up stage of less than 10 hours, the E-field can be predicted for any coil placement across the whole brain within in 2-3 milliseconds.
Proteome-wide comparison of tertiary protein structures reveal extensive molecular mimicry inPlasmodium-human interactions
Authors: Muthye Viraj , Wasmuth James D. 
Published: February 2023

AbstractMolecular mimicry is a strategy used by parasites to escape the host immune system and successfully transmit to a new host. To date, high-throughput examples of molecular mimicry have been limited to comparing protein sequences. However, with advances in the prediction of tertiary structural models, led by Deepmind’s AlphaFold, it is now possible to compare the tertiary structures of thousands of proteins from parasites and their hosts, to identify more subtle mimics. Here, we present the first proteome-level search for tertiary structure similarity between the proteins fromPlasmodium falciparumand human. Of 206P. falciparumproteins that have previously been proposed as mediators ofPlasmodium-human interactions, we propose that seven evolved to molecularly mimic a human protein. By expanding the approach to allP. falciparumproteins, we identified a further 386 potential mimics, with 51 proteins corroborated by additional biological data. These findings demonstrate a valuable application of AlphaFold-derived tertiary structural models, and we discuss key considerations for its effective use in other host-parasite systems.
Phytochrome higher order mutants reveal a complex set of light responses in the mossPhyscomitrium patens
Authors: Yuan Jinhong , Xu Tengfei , Hiltbrunner Andreas 
Published: February 2023

SUMMARYPhytochromes are photoreceptors enabling plants to respond to various light conditions. Independent gene duplication events resulted in small phytochrome gene families in mosses, ferns, and seed plants. This phytochrome diversity is hypothesised to be critical for sensing and adapting to different light conditions, but experimental evidence for this idea is lacking for mosses and ferns.The model moss speciesPhyscomitrium patenscontains seven phytochromes grouped into three clades, PHY1/3, PHY2/4, and PHY5. Here, we used CRISPR/Cas9 generated single and higher order mutants to investigate their role in light-regulation of protonema and gametophore growth, protonema branching, and induction of gametophores.We found both specific and partially overlapping roles for the three clades of moss phytochromes in regulating these responses in different light conditions, and we identified a mechanism for sensing simulated canopy shade different from the mechanism in seed plants. PHY1/3 clade phytochromes act as primary far-red light receptors, while PHY5 clade phytochromes are the primary red light receptors. PHY2/4 clade phytochromes have functions in both red and far-red light.Similar to seed plants, gene duplication events in the phytochrome lineage in mosses were followed by functional diversification into red and far-red light sensing phytochromes.
Enzyme-less nanopore detection of post-translational modifications within long polypeptides
Authors: Martin-Baniandres Pablo , Lan Wei-Hsuan , Board Stephanie , Romero-Ruiz Mercedes , Garcia-Manyes Sergi , Qing Yujia , Bayley Hagan 
Published: February 2023

AbstractMeans to sequence DNA and RNA quickly and cheaply have revolutionized biology and medicine. The ability to analyse cellular proteins and their millions of variants would be an advance of comparable importance, but requires a fresh technical approach. We use electroosmosis for the non-enzymatic capture, unfolding and translocation of individual polypeptides of more than 1200 residues by a protein nanopore. By monitoring the ionic current carried by the nanopore, we locate post-translational modifications deep within the polypeptide chains, and thereby lay the groundwork for obtaining inventories of the proteoforms in cells and tissues.
Long-term responses of Icelandic Arctic foxes to changes in marine and terrestrial ecosystems
Authors: Berthelot Fanny , Unnsteinsdóttir Ester R. , Carbonell Ellgutter Jennifer A. , Ehrich Dorothee 
Published: February 2023

AbstractThe long-term dynamics of predator populations may be driven by fluctuations in resource availability and reflect ecosystem changes such as those induced by climate change. The Icelandic Arctic fox (Vulpes lagopus) population has known major fluctuations in size since the 1950s. Using stable isotopes analysis of bone collagen over a long-time series (1979-2018), we aimed at identifying the main resources used by Icelandic Arctic foxes during periods of growth and decline to assess if the variations in their population size are linked to fluctuations in the availability of resources. We hypothesized that (1) the decline in Seabirds abundance was responsible for the decrease in the fox population; and (2) that the growth in the fox population combined to fluctuations in main resources would lead to an increase in intra-specific competition, ultimately leading to variations in their isotopic niches at the population scale. The isotopic signatures of Arctic foxes as well as their temporal trends differed clearly between inland and coast. Inland foxes showed an overall shift towards more terrestrial preys, whereas coastal foxes displayed a relatively stable use of marine resources over the years. Stable isotopes mixing models suggested that marine resources and rock ptarmigans were the most important food source and highlighted a rather stable diet in coastal habitats compared to inland habitats where more fluctuations in dietary composition were observed. Coastal foxes had a broader niche than inland foxes, and there was more variation in niche size in the inland habitat. Our results are in agreement with a general decline in seabird populations driving the decline in Arctic foxes, especially in coastal habitats. For the inland foxes, our results suggest that the lack of marine resources might have led to an increased use of ptarmigans as well as other terrestrial resources such as geese and waders, especially during the most recent period.
Does joint impedance improve dynamic leg simulations with explicit and implicit solvers?
Authors: Bahdasariants Serhii , Forti Barela Ana Maria , Gritsenko Valeriya , Bacca Odair , Angelo Barela José , Yakovenko Sergiy 
Published: February 2023

AbstractThe nervous system predicts and executes complex motion of body segments actuated by the coordinated action of muscles. When a stroke or other traumatic injury disrupts neural processing, the impeded behavior has not only kinematic but also kinetic attributes that require interpretation. Biomechanical models could allow medical specialists to observe these dynamic variables and instantaneously diagnose mobility issues that may otherwise remain unnoticed. However, the real-time and subject-specific dynamic computations necessitate the optimization these simulations. In this study, we explored the effects of intrinsic viscoelasticity, choice of numerical integration method, and decrease in sampling frequency on the accuracy and stability of the simulation. The bipedal model with 17 rotational degrees of freedom (DOF)—describing hip, knee, ankle, and standing foot contact—was instrumented with viscoelastic elements with a resting length in the middle of the DOF range of motion. The accumulation of numerical errors was evaluated in dynamic simulations using swing-phase experimental kinematics. The relationship between viscoelasticity, sampling rates, and the integrator type was evaluated. The optimal selection of these three factors resulted in an accurate reconstruction of joint kinematics (err < 1%) and kinetics (err < 5%) with increased simulation time steps. Notably, joint viscoelasticity reduced the integration errors ofexplicit methodsand had minimal to no additional benefit forimplicit methods. Gained insights have the potential to improve diagnostic tools and accurize real-time feedback simulations used in the functional recovery of neuromuscular diseases and intuitive control of modern prosthetic solutions.
Crossroad of intellectual property rights of technology innovators and human rights: a systematic literature review
Authors: Gupta Parul , Wadhwa Simran , Chauhan Sumedha 
Published: February 2023

PurposeThis paper aims to analyze the scholarly approach to examine the issues at the intersection of intellectual property rights (IPRs) and human rights (HRs) and ways to address, to examine broad categories of approaches used by the scholars in examining this conflict, their justification and to provide concrete directions for HRs framework of intellectual property.Design/methodology/approachThe study conducted systematic literature review of 94 research articles published between 1996 and 2021, focusing on cross roads between IPRs and HRs.FindingsThe in-depth content analysis of 94 published research papers revealed the polarization of scholarly opinion on the HRs perspective of IPRs.Originality/valueVery limited efforts were made in past to synthesize and organize scholarly research on the conflict between IPRs and HRs covering the right to education, to access information, to food, etc. besides the right to health care. This study synthesized and analyzed the scholarly research on the crossroad between IPRs and HRs, revealed critical conflict areas and collated the justifications of opposing approaches to provide inputs to international organizations, policymakers and governments for the enforcement of IPRs from the perspective of HRs.
Brand anthropomorphism’s impact on real estate purchase decisions of young buyers in India and the underlying reliance on spatial memory
Authors: Rodrigues Andrea , Godwin Benny J. , George Jossy P. 
Published: February 2023

PurposeAssessing anthropomorphic tendency in relation to real estate purchase decisions and analysing the elements of friendliness, aggressiveness, pleasure and arousal as a link to the spatial memory of the consumer. This study aims to help brands and advertisers in the real estate industry to create meaningful consumer relationships by using elements that are associated with positive spatial experience. By formulating a detailed questionnaire with adapted variables from proven research and a multilayered approach of theoretic and practical analysis, this paper situates the identified variables in the plane of space and customer experience.Design/methodology/approachBy using structural equation modeling, this study analyses a sample data of 411 consumers and their response to elements of housing.FindingsThe findings of this study showed that variables of friendliness, aggressiveness, pleasure and arousal significantly impact consumer’s real estate purchase decision; however, anthropomorphic tendency does not have a significant impact. Through theoretical analysis, it was found that spatial memory may have a role in the visual and display of the variables.Originality/valueThe merit of this paper lies in the discussion it has raised with regard to the intersection between theoretics of space and the chosen variables. In the field of business and management, often philosophical implications of spatiality may not be actively associated with numerical computation. This paper not only looks at brand anthropomorphism’s impact on real estate purchase decisions but also looks at friendliness and other mentioned variables as significantly impacting purchase decisions and linked to memory, space and affiliation.