bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes
Authors: Barrett Alison K. , Shingare Manisha R. , Rechtsteiner Andreas , Rodriguez Kelsie M. , Le Quynh N. , Wijeratne Tilini U. , Mitchell Corbin E. , Membreno Miles W. , Rubin Seth M. , Müller Gerd A. 
Published: May 2024

AbstractHistone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone tail deacetylation and canonically linked to transcriptional repression. Previous studies suggested that HDAC recruitment to cell-cycle gene promoters via the retinoblastoma (RB) protein or the DREAM complex through SIN3B is essential for G1/S and G2/M gene repression during cell-cycle arrest and exit. Here we investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. Knockout of SIN3B does not globally derepress cell-cycle genes in non-proliferating HCT116 and C2C12 cells. Loss of SIN3A/B moderately upregulates several cell-cycle genes in HCT116 cells but does so independently of DREAM/RB. HDAC inhibition does not induce general upregulation of RB/DREAM target genes in arrested transformed or non-transformed cells. Our findings suggest that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
Anomalous behavior of critical current in a superconducting film triggered by DC plus terahertz current
Authors: Sekiguchi Fumiya , Narita Hideki , Hirori Hideki , Ono Teruo , Kanemitsu Yoshihiko 
Published: May 2024

AbstractThe critical current in a superconductor (SC) determines the performance of many SC devices, including SC diodes which have attracted recent attention. Hitherto, studies of SC diodes are limited in the DC-field measurements, and their performance under a high-frequency current remains unexplored. Here, we conduct the first investigation on the interaction between the DC and terahertz (THz) current in a SC artificial superlattice. We found that the DC critical current is sensitively modified by THz pulse excitations in a nontrivial manner. In particular, at low-frequency THz excitations below the SC gap, the critical current becomes sensitive to the THz-field polarization direction. Furthermore, we observed anomalous behavior in which a supercurrent flows with an amplitude larger than the modified critical current. Assuming that vortex depinning determines the critical current, we show that the THz-current-driven vortex dynamics reproduce the observed behavior. While the delicate nonreciprocity in the critical current is obscured by the THz pulse excitations, the interplay between the DC and THz current causes a non-monotonic SC/normal-state switching with current amplitude, which can pave a pathway to developing SC devices with novel functionalities.
Phosphorus deficiency alleviates iron limitation in Synechocystis cyanobacteria through direct PhoB-mediated gene regulation
Authors: Qiu Guo-Wei , Zheng Wen-Can , Yang Hao-Ming , Wang Yu-Ying , Qi Xing , Huang Da , Dai Guo-Zheng , Shi Huazhong , Price Neil M. , Qiu Bao-Sheng 
Published: May 2024

AbstractIron and phosphorus are essential nutrients that exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, we show that phosphorus deficiency increases the growth of iron-limited cyanobacteria (Synechocystis sp. PCC 6803) through a PhoB-mediated regulatory network. We find that PhoB, in addition to its well-recognized role in controlling phosphate homeostasis, also regulates key metabolic processes crucial for iron-limited cyanobacteria, including ROS detoxification and iron uptake. Transcript abundances of PhoB-targeted genes are enriched in samples from phosphorus-depleted seawater, and a conserved PhoB-binding site is widely present in the promoters of the target genes, suggesting that the PhoB-mediated regulation may be highly conserved. Our findings provide molecular insights into the responses of cyanobacteria to simultaneous iron/phosphorus nutrient limitation.
A miniaturised semi-dynamic in-vitro model of human digestion
Authors: Calero Victor , Rodrigues Patrícia M. , Dias Tiago , Ainla Alar , Vilaça Adriana , Pastrana Lorenzo , Xavier Miguel , Gonçalves Catarina 
Published: May 2024

AbstractReliable in-vitro digestion models that are able to successfully replicate the conditions found in the human gastrointestinal tract are key to assess the fate and efficiency of new formulations aimed for oral consumption. However, current in-vitro models either lack the capability to replicate crucial dynamics of digestion or require large volumes of sample/reagents, which can be scarce when working with nanomaterials under development. Here, we propose a miniaturised digestion system, a digestion-chip, based on incubation chambers integrated on a polymethylmethacrylate device. The digestion-chip incorporates key dynamic features of human digestion, such as gradual acidification and gradual addition of enzymes and simulated fluids in the gastric phase, and controlled gastric emptying, while maintaining low complexity and using small volumes of sample and reagents. In addition, the new approach integrates real-time automated closed-loop control of two key parameters, pH and temperature, during the two main phases of digestion (gastric and intestinal) with an accuracy down to ± 0.1 °C and ± 0.2 pH points. The experimental results demonstrate that the digestion-chip successfully replicates the gold standard static digestion INFOGEST protocol and that the semi-dynamic digestion kinetics can be reliably fitted to a first kinetic order model. These devices can be easily adapted to dynamic features in an automated, sensorised, and inexpensive platform and will enable reliable, low-cost and efficient assessment of the bioaccessibility of new and expensive drugs, bioactive ingredients or nanoengineered materials aimed for oral consumption, thereby avoiding unnecessary animal testing.
Dynamics of invariant solutions of the DNA model using Lie symmetry approach
Authors: Hussain Akhtar , Usman Muhammad , Zidan Ahmed M. , Sallah Mohammed , Owyed Saud , Rahimzai Ariana Abdul 
Published: May 2024

AbstractThe utilization of the Lie group method serves to encapsulate a diverse array of wave structures. This method, established as a robust and reliable mathematical technique, is instrumental in deriving precise solutions for nonlinear partial differential equations (NPDEs) across a spectrum of domains. Its applications span various scientific disciplines, including mathematical physics, nonlinear dynamics, oceanography, engineering sciences, and several others. This research focuses specifically on the crucial molecule DNA and its interaction with an external microwave field. The Lie group method is employed to establish a five-dimensional symmetry algebra as the foundational element. Subsequently, similarity reductions are led by a system of one-dimensional subalgebras. Several invariant solutions as well as a spectrum of wave solutions is obtained by solving the resulting reduced ordinary differential equations (ODEs). These solutions govern the longitudinal displacement in DNA, shedding light on the characteristics of DNA as a significant real-world challenge. The interactions of DNA with an external microwave field manifest in various forms, including rational, exponential, trigonometric, hyperbolic, polynomial, and other functions. Mathematica simulations of these solutions confirm that longitudinal displacements in DNA can be expressed as periodic waves, optical dark solitons, singular solutions, exponential forms, and rational forms. This study is novel as it marks the first application of the Lie group method to explore the interaction of DNA molecules.
Speed of heart rate changes during postural provocations in children and adolescents
Authors: Šišáková Martina , Helánová Kateřina , Hnatkova Katerina , Andršová Irena , Novotný Tomáš , Malik Marek 
Published: May 2024

AbstractHeart rate is under constant autonomic influence but the development of the influence in children is not fully understood. Continuous electrocardiograms were obtained in 1045 healthy school-age children (550 females) during postural provocations with body position changes between supine, sitting, standing, supine, standing, sitting and supine (in this order), 10 min in each position with position changes within 20 s. Heart rate was measured in each position and speed of heart rate changes between positions were assessed by regressions of rates versus timing of individual cardiac cycles. Supine heart rate was gradually decreasing with age: 82.32 ± 9.92, 74.33 ± 9.79, 67.43 ± 9.45 beats per minute (bpm) in tertile age groups < 11, 11–15, > 15 years, respectively (p < 0.0001), with no significant sex difference. Averaged speed of heart rate changes differed little between sexes and age groups but was significantly faster during rate deceleration than acceleration (e.g., supine ↔ standing: 2.99 ± 1.02 vs. 2.57 ± 0.68 bpm/s, p < 0.0001). The study suggests that in children, vagal heart rate control does not noticeably change between ages of approximately 6–19 years. The gradual resting heart rate decrease during childhood and adolescence is likely caused by lowering of cardiac sympathetic influence from sympathetic overdrive in small children to adult-like sympatho-vagal balance in older adolescents.
Fluorophore multimerization on a PEG backbone as a concept for signal amplification and lifetime modulation
Authors: Reiber Thorge , Hübner Oskar , Dose Christian , Yushchenko Dmytro A. , Resch-Genger Ute 
Published: May 2024

AbstractFluorescent labels have strongly contributed to many advancements in bioanalysis, molecular biology, molecular imaging, and medical diagnostics. Despite a large toolbox of molecular and nanoscale fluorophores to choose from, there is still a need for brighter labels, e.g., for flow cytometry and fluorescence microscopy, that are preferably of molecular nature. This requires versatile concepts for fluorophore multimerization, which involves the shielding of dyes from other chromophores and possible quenchers in their neighborhood. In addition, to increase the number of readout parameters for fluorescence microscopy and eventually also flow cytometry, control and tuning of the labels’ fluorescence lifetimes is desired. Searching for bright multi-chromophoric or multimeric labels, we developed PEGylated dyes bearing functional groups for their bioconjugation and explored their spectroscopic properties and photostability in comparison to those of the respective monomeric dyes for two exemplarily chosen fluorophores excitable at 488 nm. Subsequently, these dyes were conjugated with anti-CD4 and anti-CD8 immunoglobulins to obtain fluorescent conjugates suitable for the labeling of cells and beads. Finally, the suitability of these novel labels for fluorescence lifetime imaging and target discrimination based upon lifetime measurements was assessed. Based upon the results of our spectroscopic studies including measurements of fluorescence quantum yields (QY) and fluorescence decay kinetics we could demonstrate the absence of significant dye-dye interactions and self-quenching in these multimeric labels. Moreover, in a first fluorescence lifetime imaging (FLIM) study, we could show the future potential of this multimerization concept for lifetime discrimination and multiplexing.
Circulating serum fibroblast growth factor 21 as risk and prognostic biomarker of retinal artery occlusion
Authors: Shi Ruobing , Liu Hang , Xia Kaichao , Li Ying , chen Ting , Li Xuejie , Yang Anhuai , Xiao Xuan 
Published: May 2024

AbstractTo evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case–control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.
Comparison of CTX-M encoding plasmids present during the early phase of the ESBL pandemic in western Sweden
Authors: Wranne Moa S. , Karami Nahid , KK Sriram , Jaén-Luchoro Daniel , Yazdanshenas Shora , Lin Yii-Lih , Kabbinale Arpitha , Flach Carl-Fredrik , Westerlund Fredrik , Åhrén Christina 
Published: May 2024

AbstractPlasmids encoding blaCTX-M genes have greatly shaped the evolution of E. coli producing extended-spectrum beta-lactamases (ESBL-E. coli) and adds to the global threat of multiresistant bacteria by promoting horizontal gene transfer (HGT). Here we screened the similarity of 47 blaCTX-M -encoding plasmids, from 45 epidemiologically unrelated and disperse ESBL-E. coli strains, isolated during the early phase (2009–2014) of the ESBL pandemic in western Sweden. Using optical DNA mapping (ODM), both similar and rare plasmids were identified. As many as 57% of the plasmids formed five ODM-plasmid groups of at least three similar plasmids per group. The most prevalent type (28%, IncIl, pMLST37) encoded blaCTX-M-15 (n = 10), blaCTX-M-3 (n = 2) or blaCTX-M-55 (n = 1). It was found in isolates of various sequence types (STs), including ST131. This could indicate ongoing local HGT as whole-genome sequencing only revealed similarities with a rarely reported, IncIl plasmid. The second most prevalent type (IncFII/FIA/FIB, F1:A2:B20) harboring blaCTX-M-27, was detected in ST131-C1-M27 isolates, and was similar to plasmids previously reported for this subclade. The results also highlight the need for local surveillance of plasmids and the importance of temporospatial epidemiological links so that detection of a prevalent plasmid is not overestimated as a potential plasmid transmission event in outbreak investigations.
Chronic insomnia, high trait anxiety and their comorbidity as risk factors for incident type 2 diabetes mellitus
Authors: Duquenne Pauline , Samieri Cécilia , Chambaron Stéphanie , Brindisi Marie-Claude , Kesse-Guyot Emmanuelle , Galan Pilar , Hercberg Serge , Touvier Mathilde , Léger Damien , Fezeu Léopold K. , Andreeva Valentina A. 
Published: May 2024

AbstractThe main objective of this study was to evaluate the association of the insomnia-anxiety comorbidity with incident type 2 diabetes (T2D) in a large prospective cohort. We selected adults without diabetes at baseline from the French NutriNet-Santé cohort who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (STAI-T, 2013–2016) and a sleep questionnaire (2014); insomnia was defined according to established criteria. Using multivariable Cox models, we compared T2D risk across 4 groups: no insomnia or anxiety (reference), insomnia alone, anxiety alone (STAI-T ≥ 40), and comorbid anxiety and insomnia. Among 35,014 participants (mean baseline age: 52.4 ± 14.0 years; 76% women), 378 (1.1%) developed T2D over a mean follow-up of 5.9 ± 2.1 years. Overall, 28.5% of the sample had anxiety alone, 7.5%—insomnia alone, and 12.5%—both disorders. In the fully-adjusted model, a higher T2D risk was associated with anxiety-insomnia comorbidity (HR = 1.40; 95% CI 1.01, 1.94), but not with each disorder separately, compared to the group without insomnia or anxiety. The findings supported a positive association between anxiety-insomnia comorbidity and incident T2D among general-population adults. Future research using clinical diagnoses of mental disorders could confirm the findings and guide diabetes prevention programs.
A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy
Authors: Meeusen Hester , Romagnolo Alessia , Holsink Sophie A. C. , van den Broek Thijs J. M. , van Helvoort Ardy , Gorter Jan A. , van Vliet Erwin A. , Verkuyl J. Martin , Silva Jose P. , Aronica Eleonora 
Published: May 2024

AbstractThe classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.
Computational prediction of new therapeutic effects of probiotics
Authors: Sulaimany Sadegh , Farahmandi Kajal , Mafakheri Aso 
Published: May 2024

AbstractProbiotics are living microorganisms that provide health benefits to their hosts, potentially aiding in the treatment or prevention of various diseases, including diarrhea, irritable bowel syndrome, ulcerative colitis, and Crohn’s disease. Motivated by successful applications of link prediction in medical and biological networks, we applied link prediction to the probiotic-disease network to identify unreported relations. Using data from the Probio database and International Classification of Diseases-10th Revision (ICD-10) resources, we constructed a bipartite graph focused on the relationship between probiotics and diseases. We applied customized link prediction algorithms for this bipartite network, including common neighbors, Jaccard coefficient, and Adamic/Adar ranking formulas. We evaluated the results using Area under the Curve (AUC) and precision metrics. Our analysis revealed that common neighbors outperformed the other methods, with an AUC of 0.96 and precision of 0.6, indicating that basic formulas can predict at least six out of ten probable relations correctly. To support our findings, we conducted an exact search of the top 20 predictions and found six confirming papers on Google Scholar and Science Direct. Evidence suggests that Lactobacillus jensenii may provide prophylactic and therapeutic benefits for gastrointestinal diseases and that Lactobacillus acidophilus may have potential activity against urologic and female genital illnesses. Further investigation of other predictions through additional preclinical and clinical studies is recommended. Future research may focus on deploying more powerful link prediction algorithms to achieve better and more accurate results.
Constitutional mismatch repair deficiency mimicking Lynch syndrome is associated with hypomorphic mismatch repair gene variants
Authors: Gallon Richard , Brekelmans Carlijn , Martin Marie , Bours Vincent , Schamschula Esther , Amberger Albert , Muleris Martine , Colas Chrystelle , Dekervel Jeroen , De Hertogh Gert , Coupier Jérôme , Colleye Orphal , Sepulchre Edith , Burn John , Brems Hilde , Legius Eric , Wimmer Katharina 
Published: May 2024

AbstractLynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are distinct cancer syndromes caused, respectively, by mono- and bi-allelic germline mismatch repair (MMR) variants. LS predisposes to mainly gastrointestinal and genitourinary cancers in adulthood. CMMRD predisposes to brain, haematological, and LS-spectrum cancers from childhood. Two suspected LS patients with first cancer diagnosis aged 27 or 38 years were found to be homozygous for an MMR (likely) pathogenic variant, MSH6 c.3226C>T (p.(Arg1076Cys)), or variant of uncertain significance (VUS), MLH1 c.306G>A (p.(Glu102=)). MLH1 c.306G>A was shown to cause leaky exon 3 skipping. The apparent genotype-phenotype conflict was resolved by detection of constitutional microsatellite instability in both patients, a hallmark feature of CMMRD. A hypomorphic effect of these and other variants found in additional late onset CMMRD cases, identified by literature review, likely explains a LS-like phenotype. CMMRD testing in carriers of compound heterozygous or homozygous MMR VUS may find similar cases and novel hypomorphic variants. Individualised management of mono- and bi-allelic carriers of hypomorphic MMR variants is needed until we better characterise the associated phenotypes.
Tailored plasmon polariton landscape in graphene/boron nitride patterned heterostructures
Authors: Golenić Neven , de Gironcoli Stefano , Despoja Vito 
Published: May 2024

AbstractSurface plasmon polaritons (SPPs), which are electromagnetic modes representing collective oscillations of charge density coupled with photons, have been extensively studied in graphene. This has provided a solid foundation for understanding SPPs in 2D materials. However, the emergence of wafer-transfer techniques has led to the creation of various quasi-2D van der Waals heterostructures, highlighting certain gaps in our understanding of their optical properties in relation to SPPs. To address this, we analyzed electromagnetic modes in graphene/hexagonal-boron-nitride/graphene heterostructures on a dielectric Al2O3 substrate using the full ab initio RPA optical conductivity tensor. Our theoretical model was validated through comparison with recent experiments measuring evanescent in-phase Dirac and out-of-phase acoustic SPP branches. Furthermore, we investigate how the number of plasmon branches and their dispersion are sensitive to variables such as layer count and charge doping. Notably, we demonstrate that patterning of the topmost graphene into nanoribbons provides efficient Umklapp scattering of the bottommost Dirac plasmon polariton (DP) into the radiative region, resulting in the conversion of the DP into a robust infrared-active plasmon. Additionally, we show that the optical activity of the DP and its hybridization with inherent plasmon resonances in graphene nanoribbons are highly sensitive to the doping of both the topmost and bottommost graphene layers. By elucidating these optical characteristics, we aspire to catalyze further advancements and create new opportunities for innovative applications in photonics and optoelectronic integration.