bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decrypting the programming of β-methylation in virginiamycin M biosynthesis
Authors: Collin Sabrina , Cox Russell J. , Paris Cédric , Jacob Christophe , Chagot Benjamin , Weissman Kira J. , Gruez Arnaud 
Published: March 2023

AbstractDuring biosynthesis by multi-modular trans-AT polyketide synthases, polyketide structural space can be expanded by conversion of initially-formed electrophilic β-ketones into β-alkyl groups. These multi-step transformations are catalysed by 3-hydroxy-3-methylgluratryl synthase cassettes of enzymes. While mechanistic aspects of these reactions have been delineated, little information is available concerning how the cassettes select the specific polyketide intermediate(s) to target. Here we use integrative structural biology to identify the basis for substrate choice in module 5 of the virginiamycin M trans-AT polyketide synthase. Additionally, we show in vitro that module 7, at minimum, is a potential additional site for β-methylation. Indeed, analysis by HPLC-MS coupled with isotopic labelling and pathway inactivation identifies a metabolite bearing a second β-methyl at the expected position. Collectively, our results demonstrate that several control mechanisms acting in concert underpin β-branching programming. Furthermore, variations in this control – whether natural or by design – open up avenues for diversifying polyketide structures towards high-value derivatives.
Ultrahigh loading dry-process for solvent-free lithium-ion battery electrode fabrication
Authors: Ryu Minje , Hong Young-Kuk , Lee Sang-Young , Park Jong Hyeok 
Published: March 2023

AbstractThe current lithium-ion battery (LIB) electrode fabrication process relies heavily on the wet coating process, which uses the environmentally harmful and toxic N-methyl-2-pyrrolidone (NMP) solvent. In addition to being unsustainable, the use of this expensive organic solvent substantially increases the cost of battery production, as it needs to be dried and recycled throughout the manufacturing process. Herein, we report an industrially viable and sustainable dry press-coating process that uses the combination of multiwalled carbon nanotubes (MWNTs) and polyvinylidene fluoride (PVDF) as a dry powder composite and etched Al foil as a current collector. Notably, the mechanical strength and performance of the fabricated LiNi0.7Co0.1Mn0.2O2 (NCM712) dry press-coated electrodes (DPCEs) far exceed those of conventional slurry-coated electrodes (SCEs) and give rise to high loading (100 mg cm−2, 17.6 mAh cm−2) with impressive specific energy and volumetric energy density of 360 Wh kg−1 and 701 Wh L−1, respectively.
Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis
Authors: Gönczi Mónika , Teixeira João M. C. , Barrera-Vilarmau Susana , Mediani Laura , Antoniani Francesco , Nagy Tamás Milán , Fehér Krisztina , Ráduly Zsolt , Ambrus Viktor , Tőzsér József , Barta Endre , Kövér Katalin E. , Csernoch László , Carra Serena , Fuxreiter Monika 
Published: March 2023

AbstractDuring muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, we observed Mef2D mobile nuclear condensates in C2C12 cells, similar to those formed through liquid-liquid phase separation. In addition, we found Mef2D solid-like aggregates in the cytosol, the presence of which correlated with higher transcriptional activity. In parallel, we observed a progress in the early phase of myotube development, and higher MyoD and desmin expression. In accord with our predictions, the formation of aggregates was promoted by rigid β-domain variants, as well as by a disordered β-domain variant, capable of switching between liquid-like and solid-like higher-order states. Along these lines, NMR and molecular dynamics simulations corroborated that the β-domain can sample both ordered and disordered interactions leading to compact and extended conformations. These results suggest that β-domain fine-tunes Mef2D higher-order assembly to the cellular context, which provides a platform for myogenic regulatory factors and the transcriptional apparatus during the developmental process.
Immune subset-committed proliferating cells populate the human foetal intestine throughout the second trimester of gestation
Authors: Guo Nannan , Li Na , Jia Li , Jiang Qinyue , Schreurs Mette , van Unen Vincent , de Sousa Lopes Susana M. Chuva , Vloemans Alexandra A. , Eggermont Jeroen , Lelieveldt Boudewijn , Staal Frank J. T. , de Miranda Noel F. C. C. , Pascutti M. Fernanda , Koning Frits 
Published: March 2023

AbstractThe intestine represents the largest immune compartment in the human body, yet its development and organisation during human foetal development is largely unknown. Here we show the immune subset composition of this organ during development, by longitudinal spectral flow cytometry analysis of human foetal intestinal samples between 14 and 22 weeks of gestation. At 14 weeks, the foetal intestine is mainly populated by myeloid cells and three distinct CD3–CD7+ ILC, followed by rapid appearance of adaptive CD4+, CD8+ T and B cell subsets. Imaging mass cytometry identifies lymphoid follicles from week 16 onwards in a villus-like structure covered by epithelium and confirms the presence of Ki-67+ cells in situ within all CD3–CD7+ ILC, T, B and myeloid cell subsets. Foetal intestinal lymphoid subsets are capable of spontaneous proliferation in vitro. IL-7 mRNA is detected within both the lamina propria and the epithelium and IL-7 enhances proliferation of several subsets in vitro. Overall, these observations demonstrate the presence of immune subset-committed cells capable of local proliferation in the developing human foetal intestine, likely contributing to the development and growth of organized immune structures throughout most of the 2nd trimester, which might influence microbial colonization upon birth.
3D printing of dynamic covalent polymer network with on-demand geometric and mechanical reprogrammability
Authors: Fang Zizheng , Shi Yunpeng , Mu Hongfeng , Lu Runzhi , Wu Jingjun , Xie Tao 
Published: March 2023

AbstractDelicate geometries and suitable mechanical properties are essential for device applications of polymer materials. 3D printing offers unprecedented versatility, but the geometries and mechanical properties are typically fixed after printing. Here, we report a 3D photo-printable dynamic covalent network that can undergo two independently controllable bond exchange reactions, allowing reprogramming the geometry and mechanical properties after printing. Specifically, the network is designed to contain hindered urea bonds and pendant hydroxyl groups. The homolytic exchange between hindered urea bonds allows reconfiguring the printed shape without affecting the network topology and mechanical properties. Under different conditions, the hindered urea bonds are transformed into urethane bonds via exchange reactions with hydroxyl groups, which permits tailoring of the mechanical properties. The freedom to reprogram the shape and properties in an on-demand fashion offers the opportunity to produce multiple 3D printed products from one single printing step.
Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy
Authors: O’Toole John M. , Mathieson Sean R. , Raurale Sumit A. , Magarelli Fabio , Marnane William P. , Lightbody Gordon , Boylan Geraldine B. 
Published: March 2023

AbstractThis report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded for background abnormalities. The grading system assesses EEG attributes such as amplitude, continuity, sleep–wake cycling, symmetry and synchrony, and abnormal waveforms. Background severity was then categorised into 4 grades: normal or mildly abnormal EEG, moderately abnormal EEG, majorly abnormal EEG, and inactive EEG. The data can be used as a reference set of multi-channel EEG for neonates with HIE, for EEG training purposes, or for developing and evaluating automated grading algorithms.
A Kinase Interacting Protein 1 (AKIP1) promotes cardiomyocyte elongation and physiological cardiac remodelling
Authors: Nijholt Kirsten T. , Sánchez-Aguilera Pablo I. , Booij Harmen G. , Oberdorf-Maass Silke U. , Dokter Martin M. , Wolters Anouk H. G. , Giepmans Ben N. G. , van Gilst Wiek H. , Brown Joan H. , de Boer Rudolf A. , Silljé Herman H. W. , Westenbrink B. Daan 
Published: March 2023

AbstractA Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes physiological hypertrophy in vitro. The purpose of this study is to determine if AKIP1 promotes physiological cardiomyocyte hypertrophy in vivo. Therefore, adult male mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and wild type (WT) littermates were caged individually for four weeks in the presence or absence of a running wheel. Exercise performance, heart weight to tibia length (HW/TL), MRI, histology, and left ventricular (LV) molecular markers were evaluated. While exercise parameters were comparable between genotypes, exercise-induced cardiac hypertrophy was augmented in AKIP1-TG vs. WT mice as evidenced by an increase in HW/TL by weighing scale and in LV mass on MRI. AKIP1-induced hypertrophy was predominantly determined by an increase in cardiomyocyte length, which was associated with reductions in p90 ribosomal S6 kinase 3 (RSK3), increments of phosphatase 2A catalytic subunit (PP2Ac) and dephosphorylation of serum response factor (SRF). With electron microscopy, we detected clusters of AKIP1 protein in the cardiomyocyte nucleus, which can potentially influence signalosome formation and predispose a switch in transcription upon exercise. Mechanistically, AKIP1 promoted exercise-induced activation of protein kinase B (Akt), downregulation of CCAAT Enhancer Binding Protein Beta (C/EBPβ) and de-repression of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4 (CITED4). Concludingly, we identified AKIP1 as a novel regulator of cardiomyocyte elongation and physiological cardiac remodelling with activation of the RSK3-PP2Ac-SRF and Akt-C/EBPβ-CITED4 pathway. These findings suggest that AKIP1 may serve as a nodal point for physiological reprogramming of cardiac remodelling.
The systemic deletion of interleukin-1α reduces myocardial inflammation and attenuates ventricular remodeling in murine myocardial infarction
Authors: Lugrin J. , Parapanov R. , Milano G. , Cavin S. , Debonneville A. , Krueger T. , Liaudet L. 
Published: March 2023

AbstractMyocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1β or the IL-1 receptor. In contrast, the potential role of IL-1α in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1α may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1α deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1α deficiency (IL-1α KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1α therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation.
Kibble–Zurek scaling due to environment temperature quench in the transverse field Ising model
Authors: Bácsi Ádám , Dóra Balázs 
Published: March 2023

AbstractThe Kibble–Zurek mechanism describes defect production due to non-adiabatic passage through a critical point. Here we study its variant from ramping the environment temperature to a critical point. We find that the defect density scales as $$\tau ^{-d\nu }$$

τ

-
d
ν

or $$\tau ^{-d/z}$$

τ

-
d
/
z

for thermal or quantum critical points, respectively, in terms of the usual critical exponents and $$1/\tau$$

1
/
τ

the speed of the drive. Both scalings describe reduced defect density compared to conventional Kibble–Zurek mechanism, which stems from the enhanced relaxation due to bath-system interaction. Ramping to the quantum critical point is investigated by studying the Lindblad equation for the transverse field Ising chain in the presence of thermalizing bath, with couplings to environment obeying detailed balance, confirming the predicted scaling. The von-Neumann or the system-bath entanglement entropy follows the same scaling. Our results are generalized to a large class of dissipative systems with power-law energy dependent bath spectral densities as well.
Perspectives of French adolescents with ADHD and child and adolescent psychiatrists regarding methylphenidate use
Authors: Sibeoni Jordan , Manolios Emilie , Hausser Clement , Delage Raphael , Baylé Franck , Speranza Mario , Verneuil Laurence , Revah-Levy Anne 
Published: March 2023

AbstractMany studies have demonstrated the short-term efficacy and tolerability of methylphenidate treatment adolescents with attention deficit hyperactivity disorder (ADHD). Qualitative literature on this matter focused on school outcomes, long-term side effects, family conflicts, personality changes and stigmatization. Yet, no qualitative study has crossed the perspectives of child and adolescent psychiatrists (CAPs) prescribing methylphenidate and adolescents with ADHD. This French qualitative study followed the five stages IPSE—Inductive Process to analyze the Structure of lived Experience-approach. Fifteen adolescents with ADHD and 11 CAPs were interviewed. Data collection by purposive sampling continued until data saturation was reached. Data analysis, based on a descriptive and structuring procedure to determine the structure of lived experience characterized by the central axes of experience, produced two axes: (1) The process of methylphenidate prescription, highlighting how this prescription was motivated from the exterior, experienced as passive by the adolescents and required commitment from the CAPs; and (2) the perceived effects of methylphenidate treatment, in three domains: at school, in relationships and in the sense of self. Findings raised both the issues of the epistemic position and social representation of the adolescents about ADHD and methylphenidate within this specific French context, and the self-awareness and perception of the adolescents with ADHD. We conclude that these two issues need to be regularly addressed by the CAPs prescribing methylphenidate to avoid epistemic injustice and prevent the harmful effects of stigmatization.
Insights on the dissolution of water in an albite melt at high pressures and temperatures from a direct structural analysis
Authors: Mayanovic Robert A. , Anderson Alan J. , Romine Devon , Benmore Chris J. 
Published: March 2023

AbstractThe water dissolution mechanism in silicate melts under high pressures is not well understood. Here we present the first direct structure investigation of a water-saturated albite melt to monitor the interactions between water and the network structure of silicate melt at the molecular level. In situ high-energy X-ray diffraction was carried out on the NaAlSi3O8-H2O system at 800 °C and 300 MPa, at the Advanced Photon Source synchrotron facility. The analysis of the X-ray diffraction data was augmented with classical Molecular Dynamics simulations of a hydrous albite melt, incorporating accurate water-based interactions. The results show that metal–oxygen bond breaking at the bridging sites occurs overwhelmingly at the Si site upon reaction with H2O, with subsequent Si–OH bond formation and negligible Al–OH formation. Furthermore, we see no evidence for the dissociation of the Al3+ ion from the network structure upon breaking of the Si–O bond in the hydrous albite melt. The results also indicate that the Na+ ion is an active participant in the modifications of the silicate network structure of the albite melt upon water dissolution at high P–T conditions. We do not find evidence for the Na+ ion dissociating from the network structure upon depolymerization and subsequent formation of NaOH complexes. Instead, our results show that the Na+ ion persists as a structure modifier with a shift away from Na–BO bonding to an increase in the extent of Na-NBO bonding, in parallel with pronounced depolymerization of the network. Our MD simulations show that the Si–O and Al–O bond lengths are expanded by about 6% in the hydrous albite melt compared to those of the dry melt at high P–T conditions. The changes in the network silicate structure of a hydrous albite melt at high pressure and temperature, as revealed in this study, must be considered in the advancement of water dissolution models of hydrous granitic (or alkali aluminosilicate) melts.
Investigation of temperature variations on a Class-E inverter and proposing a compensation circuit to prevent harmful effects on biomedical implants
Authors: Khodadoost Mehrnaz , Hayati Mohsen , Abbasi Hamed 
Published: March 2023

AbstractIn this paper, a Class-E inverter and a thermal compensation circuit for wireless power transmission in biomedical implants are designed, simulated, and fabricated. In the analysis of the Class-E inverter, the voltage-dependent non-linearities of Cds, Cgd, and RONas well as temperature-dependent non-linearity of RONof the transistor are considered simultaneously. Close agreement of theoretical, simulated and experimental results confirmed the validity of the proposed approach in taking into account these nonlinear effects. The paper investigated the effect of temperature variations on the characteristics of the inverter. Since both the output power and efficiency decrease with increasing temperature, a compensation circuit is proposed to keep them constant within a wide temperature range to enable its application as a reliable power source for medical implants in harsh environments. Simulations were performed and the results confirmed that the compensator enables significant improvements by maintaining the power and efficiency almost constant (8.46 ± 0.14 W and 90.4 ± 0.2%) within the temperature range of − 60 to 100 °C. Measurements performed at 25 °C and 80 °C with and without the compensation circuit were in good agreement with the theoretical and simulation results. The obtained measured output power and efficiency at 25 °C are equal to 7.42 W and 89.9%.
Effect of high-fat diet and morning or evening exercise on lipoprotein subfraction profiles: secondary analysis of a randomised trial
Authors: Moholdt Trine , Parr Evelyn B. , Devlin Brooke L. , Giskeødegård Guro F. , Hawley John A. 
Published: March 2023

AbstractWe investigated the effect of a high-fat diet (HFD) on serum lipid subfractions in men with overweight/obesity and determined whether morning or evening exercise affected these lipid profiles. In a three-armed randomised trial, 24 men consumed an HFD for 11 days. One group of participants did not exercise (n = 8, CONTROL), one group trained at 06:30 h (n = 8, EXam), and one group at 18:30 h (n = 8, EXpm) on days 6–10. We assessed the effects of HFD and exercise training on circulating lipoprotein subclass profiles using NMR spectroscopy. Five days of HFD induced substantial perturbations in fasting lipid subfraction profiles, with changes in 31/100 subfraction variables (adjustedpvalues [q] < 0.05). Exercise training induced a systematic change in lipid subfraction profiles, with little overall difference between EXam and EXpm. Compared with CONTROL, exercise training reduced serum concentrations of > 20% of fasting lipid subfractions. EXpm reduced fasting cholesterol concentrations in three LDL subfractions by ⁓30%, while EXam only reduced concentration in the largest LDL particles by 19% (allq < 0.05). Lipid subfraction profiles changed markedly after 5 days HFD in men with overweight/obesity. Both morning and evening exercise training impacted subfraction profiles compared with no exercise.
Towards a biomarker for acute arterial thrombosis using complete blood count and white blood cell differential parameters in mice
Authors: Jang Hee Jeong , Schellingerhout Dawid , Kim Jiwon , Chung Jinyong , Kim Dong-Eog 
Published: March 2023

AbstractThere is no blood biomarker diagnostic of arterial thrombosis. We investigated if arterial thrombosis per se was associated with alterations in complete blood count (CBC) and white blood cell (WBC) differential count in mice. Twelve-week-old C57Bl/6 mice were used for FeCl3-mediated carotid thrombosis (n = 72), sham-operation (n = 79), or non-operation (n = 26). Monocyte count (/µL) at 30-min after thrombosis (median 160 [interquartile range 140–280]) was ~ 1.3-fold higher than at 30-min after sham-operation (120 [77.5–170]), and twofold higher than in non-operated mice (80 [47.5–92.5]). At day-1 and -4 post-thrombosis, compared with 30-min, monocyte count decreased by about 6% and 28% to 150 [100–200] and 115 [100–127.5], which however were about 2.1-fold and 1.9-fold higher than in sham-operated mice (70 [50–100] and 60 [30–75], respectively). Lymphocyte counts (/µL) at 1- and 4-days after thrombosis (mean ± SD; 3513 ± 912 and 2590 ± 860) were ~ 38% and ~ 54% lower than those in the sham-operated mice (5630 ± 1602 and 5596 ± 1437, respectively), and ~ 39% and ~ 55% lower than those in non-operated mice (5791 ± 1344). Post-thrombosis monocyte-lymphocyte-ratio (MLR) was substantially higher at all three time-points (0.050 ± 0.02, 0.046 ± 0.025, and 0.050 ± 0.02) vs. sham (0.003 ± 0.021, 0.013 ± 0.004, and 0.010 ± 0.004). MLR was 0.013 ± 0.005 in non-operated mice. This is the first report on acute arterial thrombosis-related alterations in CBC and WBC differential parameters.