bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of navigation in catheter-based endovascular procedures
Authors: Hartquist Chase M. , Lee Jin Vivian , Qiu Michael Y. , Suskin Charles , Chandrasekaran Vinay , Lowe Halle R. , Zayed Mohamed A. , Osbun Joshua W. , Genin Guy M. 
Published: June 2023

AbstractEndovascular procedures provide surgeons and other interventionalists with minimally invasive methods to treat vascular diseases by passing guidewires, catheters, sheaths and treatment devices into the vasculature to and navigate toward a treatment site. The efficiency of this navigation affects patient outcomes, but is frequently compromised by catheter “herniation”, in which the catheter-guidewire system bulges out from the intended endovascular pathway so that the interventionalist can no longer advance it. Here, we showed herniation to be a bifurcation phenomenon that can be predicted and controlled using mechanical characterizations of catheter-guidewire systems and patientspecific clinical imaging. We demonstrated our approach in laboratory models and, retrospectively, in patients who underwent procedures involving transradial neurovascular procedures with an endovascular pathway from the wrist, up in the arm, around the aortic arch, and into the neurovasculature. Our analyses identified a mathematical navigation stability criterion that predicted herniation in all of these settings. Results show that herniation can be predicted through bifurcation analysis, and provide a framework for selecting catheter-guidewire systems to avoid herniation in specific patient anatomy.
Microbial Responses to Biochar Soil Amendment and Influential Factors: A Three-level Meta-analysis
Authors: Kerner Patricia , Struhs Ethan , Mirkouei Amin , Aho Ken , Lohse Kathleen A , Dungan Robert S , You Yaqi 
Published: June 2023

AbstractBiochar is a multifunctional soil conditioner capable of enhancing soil health and crop production while reducing greenhouse gas emissions. Understanding how soil microbes respond to biochar amendment is a vital step towards precision biochar application. Here, we synthesized 3899 observations of 24 microbial responses from 61 primary studies, applied a three-level mixed-effects model to estimate biochar effects, and evaluated the importance of biochar characteristics (feedstock, pyrolysis temperature), soil properties (pH, C:N, cation exchange capacity, bulk or rhizosphere), and treatment protocols (application rate, fertilization, duration, field or laboratory). Biochar significantly boosts microbial abundance (microbial biomass carbon > CFU), nitrite reductase gene (nirS), the activity of C- and N-cycling enzymes (dehydrogenase > cellulase > urease > invertase), and potential nitrification rate. Biochar characteristics, soil properties, and treatment protocols strongly determine the direction and extent of microbial response changes. Feedstock, pyrolysis temperature, application rate, and soil pH are important predictors most frequently included in the final models. Our study highlights the promise of purpose-driven biochar production and application such that biochar production parameters can be tuned to elicit the desired microbial responses and application protocols could be optimized to invoke multiple benefits. It also underlines current knowledge gaps and future research needs.SynopsisMeta-analysis reveals overall effect sizes of soil microbial responses to biochar amendment and the most influential factors, highlighting the potential of purpose-driven precision biochar towards sustainable agriculture.
Conjunctive vector coding and place coding in hippocampus share a common directional signal
Authors: Zhou Yue-Qing , Puliyadi Vyash , Chen Xiaojing , Lee Joonhee Leo , Zhang Lan-Yuan , Knierim James J. 
Published: June 2023

AbstractVector coding is becoming increasingly understood as a major mechanism by which neural systems represent an animal’s location in both a global reference frame and a local, item-based reference frame. Landmark vector cells (LVCs) in the hippocampus complement classic place cells by encoding the vector relationship (angle and distance) between the individual and specific landmarks in the environment. How these properties of hippocampal principal cells interact is not known. We simultaneously recorded the activities of place cells and LVCs via in vivo calcium imaging of the CA1 region of freely moving rats during classic, cue-card rotation studies. The firing fields of place cells rotated relative to the center of the platform to follow the cue card rotation, whereas the firing fields of simultaneously recorded LVCs rotated by the same amount as the place cells, but the axis of rotation was the nearby local landmarks, not the environmental center. We identified a novel type of place cell that exhibited conjunctive coding of the classic place field properties and LVC properties. These results demonstrate the capacity of CA1 neurons to encode both world-centered spatial information and animals’ location relative to the local landmarks, with a common directional input presumably provided by the head direction cell system.
Haploid-resolved and chromosome-scale genome assembly inCitrus unshiuand its parental species,C. nobilisandC. kinokuni
Authors: Isobe Sachiko , Fujii Hiroyoshi , Shirasawa Kenta , Kawahara Yoshihiro , Endo Tomoko , Shimada Takehiko 
Published: June 2023

AbstractCitrus, a member of the Rutaceae family, is a widely cultivated crop with numerous cultivars. In Japan, citrus fruits account for a significant portion of agricultural production. Although several new citrus varieties have been developed through conventional breeding programs, satsuma mandarin remains the dominant cultivar. In this study, chromosome-scale and haploid-resolved reference genome sequences of satsuma mandarin (Citrus unshiuMarc) and its parental varaieties, kishu mandarin (C. kinokunihort. ex Tanaka) and kunenbo mandarin (C. nobilisLour. var. kunip Tanaka) were generated using long-read sequencing and Hi-C technologies. The comparison of haploid and unphased genomes revealed structural differences between them, indicating distinct regions in each haploid. In addition, genetic linkage maps were constructed, and genetic and physical distances were compared. The results showed variations in polymorphism density across different regions of the chromosomes. Together, the obtained results provide valuable insights into the genomic characteristics and structural variations of satsuma mandarin and related citrus varieties. These insights will lead to the further elucidation and improvement of citrus cultivars through genome breeding strategies.
Melatonin suppression by light involves different retinal photoreceptors in young and older adults
Authors: Najjar Raymond P. , Prayag Abhishek S. , Gronfier Claude 
Published: June 2023

AbstractIntroductionAge-related sleep and circadian rhythm disturbances may be due to altered non-visual photoreception. Here, we investigated the temporal dynamics of light-induced melatonin suppression in young and older individuals.MethodsIn a within-subject design study, young and older participants were exposed for 60 minutes (0030-0130 at night) to 9 narrow-band lights (range: 420 to 620 nm). Plasma melatonin suppression was calculated at 15, 30, 45, and 60 min time intervals. Individual spectral sensitivity of melatonin suppression and photoreceptor contribution were predicted for each interval and age group.ResultsIn young participants, melanopsin solely drove melatonin suppression at all time intervals, with an invariant peak sensitivity at ∼485 nm established only after 15 minutes of light exposure. Conversely, in older participants, spectral light-driven melatonin suppression was best explained by a model combining melanopsin + L-cones with a stable peak sensitivity (∼499 nm) at 30, 45, and 60 minutes of light exposure.ConclusionAging is associated with a distinct photoreceptor contribution to melatonin suppression by light. While in young adults melanopsin-only photoreception is a reliable predictor of melatonin suppression, in older individuals this process is jointly driven by melanopsin and L-cones. These findings offer new prospects for customizing light therapy for older individuals.
Mutation in mitochondrial chaperone TRAP1 results in male-specific autism
Authors: Rydzanicz Małgorzata , Kuzniewska Bozena , Magnowska Marta , Wójtowicz Tomasz , Borsuk Ewa , Gewartowska Olga , Gruchota Jakub , Hojka Anna , Miłek Jacek , Stawikowska Aleksandra , Wardaszka Patrycja , Chojnicka Izabela , Kondrakiewicz Ludwika , Puścian Alicja , Knapska Ewelina , Dziembowski Andrzej , Płoski Rafał , Dziembowska Magdalena 
Published: June 2023

AbstractThere is increasing evidence of mitochondrial dysfunction in autism spectrum disorders (ASD), but the causal relationships are unclear. In an ASD patient whose identical twin was unaffected, we identified a postzygotic mosaic mutation p.Q639* in theTRAP1gene, which encodes a mitochondrial chaperone of the HSP90 family. Additional screening of 176 unrelated ASD probands revealed an identicalTRAP1variant in a male patient who had inherited it from a healthy mother. Notably, newly generated knock-inTrap1p.Q641* mice display ASD-related behavioral abnormalities exclusively in males. Accordingly,Trap1p.Q641* mutation also resulted in sex-specific changes in synaptic plasticity, number of presynaptic mitochondria, and metabolic substrate consumption. Thus, theTRAP1p.Q639* mutation is the first example of a monogenic ASD caused by impaired mitochondrial protein homeostasis.One-Sentence SummaryPatient mutation inTRAP1causes autism in male mice.
Antibody Complementarity-Determining Region Sequence Design using AlphaFold2 and Binding Affinity Prediction Model
Authors: Ueki Takafumi , Ohue Masahito 
Published: June 2023

AbstractAffinity maturation in the immune response is limited in terms of affinity gain, and natural antibodies often do not have the binding affinity required for therapeutic applications. Therefore, improving the binding affinity of antibodies is essential for developing antibody-based therapeutics. Designing antibodies using experimental methods is expensive in terms of cost and time owing to the large range of complementarity-determining regions to be explored. Recently, computational methods have been developed as low-cost and fast means of designing and redesigning antibodies. This study evaluated the design performance of AlphaFold2 and the binder hallucination, which can predict protein 3D structures with high accuracy even without experimental antibodies, by redesigning antibody sequences to improve the binding affinity of existing antigen-antibody complexes. Therefore, antibody sequences with higher affinity can be designed for antigen-antibody complexes not included in the training data of AlphaFold2, indicating that the proposed method may be effective as an antibody design method.
Explaining Deep Neural Networks for the Prediction of Translation Rates
Authors: Korbel Frederick , Eroshok Ekaterina , Ohler Uwe 
Published: June 2023

AbstractA recent convolutional neural network model accurately quantifies the relationship between massively parallel synthetic 5’ untranslated regions (5’UTRs) and translation levels, but the underlying sequence determinants remain elusive. Applying model interpretation, we extract representations of regulatory logic, revealing a complex interplay of regulatory sequence elements. Guided by insights from model interpretation, we adapt the model by human reporter data to obtain superior performance, which will promote applications in synthetic biology and precision medicine.
HDAC4-mediated deacetylation of GSDMD prevents pyroptosis by inhibiting GSDMD ubiquitination
Authors: Xu Weilv , Li Xinyue , Li Danyue , Fu Xinyu , Chen Nan , Lv Qian , Shi Yuhua , He Suhui , Dong Lu , Yang Yang , Shi Fushan 
Published: June 2023

AbstractGasdermin D (GSDMD) functions as a key pyroptotic executor and induces cytokine secretion after cleavage by inflammatory caspases. However, less is known about the role of posttranslational modifications (PTMs) in GSDMD-mediated pyroptosis. Here, we report that GSDMD can be acetylated at Lysine 248 residue and the acetylation of GSDMD promotes pyroptosis. We identified histone deacetylase 4 (HDAC4) as the specific deacetylase that mediates GSDMD deacetylation and subsequent pyroptosis inhibitionin vitroandin vivo. GSDMD deacetylation impairs the ubiquitination of GSDMD, for which pyroptosis is inhibited. Interestingly, the phosphorylation of HDAC4 is important for its ability of deacetylating GSDMD and suppressing GSDMD-mediated pyroptosis. The Protein phosphatase 1 (PP1) catalytic subunits (PP1α and PP1γ) mediate the dephosphorylation of HDAC4, thereby abrogating its deacetylase activity on GSDMD. Therefore, our work unravels a complex regulatory mechanism involving HDAC4, PP1 and GSDMD, and provides novel insights into the crosstalk among acetylation, ubiquitination and phosphorylation.
In silicosimulations reveal molecular mechanism of uranyl ion toxicity towards DNA-binding domain of PARP-1 protein
Authors: Bulavko Egor S. , Ivankov Dmitry N. 
Published: June 2023

AbstractThe molecular toxicity of uranyl ion (UO22+) in living cells is mainly conditioned by its high affinity to both native and potential metal-binding sites frequently occurring in biomolecules structure. Recent advances in computational and experimental research shed light on the structural properties and functional impacts of uranyl binding to proteins, organic ligands, nucleic acids and their complexes. In the present work, we report the results of the theoretical investigation of the uranyl-mediated loss of DNA-binding activity of PARP-1, eukaryotic enzyme that participates in DNA reparation, cell differentiation, induction of inflammation, etc. Latest experimental studies showed that uranyl ion directly interacts with its DNA-binding subdomains – zinc fingers Zn1 and Zn2, – and changes their tertiary structure. Here, we propose an atomistic mechanism underlying this process and compute the free energy change along the suggested pathway to prove its relevance. According to the results of our QM/MM simulations of Zn2-UO22+complex, uranyl ion replaces zinc in its native binding site, but the corresponding state is destroyed because of the following spontaneous internal hydrolysis of the U–Cys162 coordination bond. Although the enthalpy of hydrolysis is +2.8 kcal/mol, the final value of the free energy of the reaction constitutes -0.6 kcal/mol, due to structure loosening evidenced by solvation and configuration thermodynamic properties calculated using GIST- and MIST-based trajectory processing techniques. The subsequent reorganization of the binding site includes association of uranyl ion with the Glu190/Asp191 acidic cluster and significant perturbations in the domain’s tertiary structure, which further decreases the free energy of the non-functional state by 6.8 kcal/mol. The disruption of the DNA-binding interface revealed in our computational simulations is consistent with previous experimental findings and appears to be associated with the loss of the Zn2 affinity for nucleic acids.
Tactile Imagery Affects Cortical Responses to Vibrotactile Stimulation of the Fingertip
Authors: Morozova Marina , Yakovlev Lev , Syrov Nikolay , Perevoznyuk Gleb , Lebedev Mikhail , Kaplan Alexander 
Published: June 2023

AbstractAlthough imagery of tactile sensations is not so well studied compared to other types of mental imagery, it is potentially very useful for brain computer interfaces (BCIs) where it could produce neural modulations needed for BCI operations. Here we assessed neural modulations associated with tactile imagery (TI) by comparing its effects on cortical responses to the effects of actual vibrotactile stimulation of the fingertip. We found that both TI and vibrostimulation evoked event-related frequency changes of the electroencephalographic (EEG) activity. Moreover, TI affected somatosensory evoked potentials (SEPs) evoked by short pulses of vibration. EEG data were collected in 29 participants trained to perform tactile imagery task. Responses to vibratory pulses were measured with and without TI. These SEPs consisted of three prominent components: a P100 response in the centro-parietal regions, a P200 response in the frontal region, and a P300 response in the central regions. The TI consistently resulted in an increase in ipsilateral P100, ipsi- and contralateral P300 and frontal P200. Moreover, TI strengthened the θ-band ERS in the frontal region that occurred in response to vibration. These findings suggest that TI not only modulates EEG patterns by itself but also affects cortical processing of physical somatosensory stimuli. Such conjoint processing of both real and imagined somatic sensations could be utilized in BCIs, particularly in clinically relevant BCI that strive to restore somatosensory processing by combining centrally-induced and peripheral activities.Significance StatementWhile it is known that tactile imagery (TI) engages the same cortical areas that are active during the processing of real tactile inputs, neural mechanisms of such shared representation are not well understood. This study employed EEG recordings to examine the interaction between real and imagined somatic sensations. It was found that TI both changes EEG oscillatory activity and facilitates cortical responses to real tactile stimuli. Therefore combining TI with tactile stimulation could be useful for tactile-based brain-computer interfaces (BCIs), particularly the ones of clinical utility for neurorehabilitation and sensory substitution.
Machine Learning-Guided Antibody Engineering That Leverages Domain Knowledge To Overcome The Small Data Problem
Authors: Clark Thomas , Subramanian Vidya , Jayaraman Akila , Fitzpatrick Emmett , Gopal Ranjani , Pentakota Niharika , Rurak Troy , Anand Shweta , Viglione Alexander , Raman Rahul , Tharakaraman Kannan , Sasisekharan Ram 
Published: June 2023

AbstractThe application of Machine Learning (ML) tools to engineer novel antibodies having predictable functional properties is gaining prominence. Herein, we present a platform that employs an ML-guided optimization of the complementarity-determining region (CDR) together with a CDR framework (FR) shuffling method to engineer affinity-enhanced and clinically developable monoclonal antibodies (mAbs) from a limited experimental screen space (order of 10^2 designs) using only two experimental iterations. Although high-complexity deep learning models like graph neural networks (GNNs) and large language models (LLMs) have shown success on protein folding with large dataset sizes, the small and biased nature of the publicly available antibody-antigen interaction datasets is not sufficient to capture the diversity of mutations virtually screened using these models in an affinity enhancement campaign. To address this key gap, we introduced inductive biases learned from extensive domain knowledge on protein-protein interactions through feature engineering and selected model hyper parameters to reduce overfitting of the limited interaction datasets. Notably we show that this platform performs better than GNNs and LLMs on an in-house validation dataset that is enriched in diverse CDR mutations that go beyond alanine-scanning. To illustrate the broad applicability of this platform, we successfully solved a challenging problem of redesigning two different anti-SARS-COV-2 mAbs to enhance affinity (up to 2 orders of magnitude) and neutralizing potency against the dynamically evolving SARS-COV-2 Omicron variants.
α-synuclein promotes neuronal dysfunction and death by disrupting the binding of ankyrin to ß-spectrin
Authors: Maor Gali , Dubreuil Ronald R. , Feany Mel B. 
Published: June 2023

Abstractα-synuclein plays a key role in the pathogenesis of Parkinson’s disease and related disorders, but critical interacting partners and molecular mechanisms mediating neurotoxicity are incompletely understood. We show that α-synuclein binds directly to ß-spectrin. Using males and females in aDrosophilamodel of α-synuclein-related disorders we demonstrate that ß-spectrin is critical for α-synuclein neurotoxicity. Further, the ankyrin binding domain of ß-spectrin is required for α-synuclein binding and neurotoxicity. A key plasma membrane target of ankyrin, Na+/K+ATPase, is mislocalized when human α-synuclein is expressed inDrosophila. Accordingly, membrane potential is depolarized in α-synuclein transgenic fly brains. We examine the same pathway in human neurons and find that Parkinson’s disease patient-derived neurons with a triplication of the α-synuclein locus show disruption of the spectrin cytoskeleton, mislocalization of ankyrin and Na+/K+ATPase, and membrane potential depolarization. Our findings define a specific molecular mechanism by which elevated levels of α-synuclein in Parkinson’s disease and related α-synucleinopathies leads to neuronal dysfunction and death.Significance StatementThe small synaptic vesicle associate protein α-synuclein plays a critical role in the pathogenesis of Parkinson’s disease and related disorders, but the disease-relevant binding partners of α-synuclein and proximate pathways critical for neurotoxicity require further definition. We show that α-synuclein binds directly to ß-spectrin, a key cytoskeletal protein required for localization of plasma membrane proteins and maintenance of neuronal viability. Binding of α-synuclein to ß-spectrin alters the organization of the spectrin-ankyrin complex, which is critical for localization and function of integral membrane proteins, including Na+/K+ATPase. These finding outline a previously undescribed mechanism of α-synuclein neurotoxicity and thus suggest potential new therapeutic approaches in Parkinson’s disease and related disorders.
Hyperaccumulation of Vanadium in animals: two sponges compete with urochordates
Authors: de Pao Mendonca Kassandra , Chaurand Perrine , Campos Andrea , Angeletti Bernard , Rovezzi Mauro , Delage Ludovic , Borchiellini Carole , Bivic André Le , Issartel Julien , Renard Emmanuelle , Levard Clément 
Published: June 2023

AbstractVanadium (V) is the second most abundant transition metal in the oceans. Nevertheless, its concentration in organisms is generally low despite its involvement in various physiological or enzymatic functions. Because exposure to high concentrations was shown to be harmful for various organisms including animals, the unexpected very high concentrations found in urochordates and annelids yielded additional studies to decipher their biological meaning.Here we report cases of V hyperaccumulators in a distinct animal phylum (Porifera): the two homoscleromorph sponge speciesOscarella lobularisandOscarella tuberculata(up to 30 mg/g dw). These high concentrations overpass those reported previously in urochordates and annelids and are not found in the 5 other sponge species studied here. In bothOscarellaspecies, vanadium is mainly accumulated in the 100 μm surface tissues, and in particular in mesohylar cells, as vanadyl (+4) before being partly reduced to V (+3) in the deeper tissues. Genomic surveys failed to find any previously described gene implicated in vanadium metabolism, suggesting that V hyperaccumulation emerged convergently in this lineage. This feature may be of interest for developing bioremediation strategies in marine ecosystems or bioinspired processes to recycle this critical metal.SynopsisThis study reports extremely high concentrations of vanadium in two sponges. This unusual bioaccumulation of reduced V (+3) in mesohylar cells relies on unknown molecular mechanisms.