bluuebunny/crossref_metadata_2025 huggingface dataset:
The adaptive value of density-dependent habitat specialization and social network centrality
Authors: Webber Quinn M. R. , Laforge Michel P. , Bonar Maegwin , Vander Wal Eric
Published: May 2024

Density dependence is a fundamental ecological process. In particular, animal habitat selection and social behavior often affect fitness in a density-dependent manner. The Ideal Free Distribution (IFD) and niche variation hypothesis (NVH) present distinct predictions associated with Optimal Foraging Theory about how the effect of habitat selection on fitness varies with population density. Using caribou (Rangifer tarandus) in Canada as a model system, we test competing hypotheses about how habitat specialization, social behavior, and annual reproductive success (co)vary across a population density gradient. Within a behavioral reaction norm framework, we estimate repeatability, behavioral plasticity, and covariance among social behavior and habitat selection to investigate the adaptive value of sociality and habitat selection. In support of NVH, but not the IFD, we find that at high density habitat specialists had higher annual reproductive success than generalists, but were also less social than generalists, suggesting the possibility that specialists were less social to avoid competition. Our study supports niche variation as a mechanism for density-dependent habitat specialization.
Biochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
Authors: Sneddon Alexandra , Ravindran Agin , Shanmuganandam Somasundhari , Kanchi Madhu , Hein Nadine , Jiang Simon , Shirokikh Nikolay , Eyras Eduardo
Published: May 2024

The heterogeneous composition of cellular transcriptomes poses a major challenge for detecting weakly expressed RNA classes, as they can be obscured by abundant RNAs. Although biochemical protocols can enrich or deplete specified RNAs, they are time-consuming, expensive and can compromise RNA integrity. Here we introduce RISER, a biochemical-free technology for the real-time enrichment or depletion of RNA classes. RISER performs selective rejection of molecules during direct RNA sequencing by identifying RNA classes directly from nanopore signals with deep learning and communicating with the sequencing hardware in real time. By targeting the dominant messenger and mitochondrial RNA classes for depletion, RISER reduces their respective read counts by more than 85%, resulting in an increase in sequencing depth of 47% on average for long non-coding RNAs. We also apply RISER for the depletion of globin mRNA in whole blood, achieving a decrease in globin reads by more than 90% as well as an increase in non-globin reads by 16% on average. Furthermore, using a GPU or a CPU, RISER is faster than GPU-accelerated basecalling and mapping. RISER’s modular and retrainable software and intuitive command-line interface allow easy adaptation to other RNA classes. RISER is available at https://github.com/comprna/riser.
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

Histone 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

The 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

Iron 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

Reliable 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

The 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

Heart 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

Fluorescent 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

To 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

Plasmids 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

The 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

The 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

Probiotics 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

Lynch 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

Surface 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.
A digital twin model incorporating generalized metabolic fluxes to identify and predict chronic kidney disease in type 2 diabetes mellitus
Authors: Surian Naveenah Udaya , Batagov Arsen , Wu Andrew , Lai Wen Bin , Sun Yan , Bee Yong Mong , Dalan Rinkoo
Published: May 2024

We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts (n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification. We subsequently conducted a comprehensive study utilizing a single dataset to evaluate the clinical utility of GMF for CKD prediction. The GMF-based identification model performed strongly, achieving an AUC between 0.80 and 0.82. In prediction, the GMF generated with complete parameters attained high performance with an AUC of 0.86, while with incomplete parameters, it achieved an AUC of 0.75. The GMF-based prediction model utilizing complete inputs is the standard implementation of our algorithm: HealthVector Diabetes®. We have established the GMF digital twin-based model as a robust clinical tool capable of predicting and stratifying the risk of future CKD within a 3-year time horizon. We report the correlation of GMF with basic input parameters, their ability to differentiate between future health states and medication status at baseline, and their capability to quantify CKD progression rates. This holistic methodology provides insights into patients’ health states and CKD progression rates based on GMF metabolic profile differences, enabling personalized care plans.
Imperceptible augmentation of living systems with organic bioelectronic fibres
Authors: Wang Wenyu , Pan Yifei , Shui Yuan , Hasan Tawfique , Lei Iek Man , Ka Stanley Gong Sheng , Savin Thierry , Velasco-Bosom Santiago , Cao Yang , McLaren Susannah B. P. , Cao Yuze , Xiong Fengzhu , Malliaras George G. , Huang Yan Yan Shery
Published: May 2024

The functional and sensory augmentation of living structures, such as human skin and plant epidermis, with electronics can be used to create platforms for health management and environmental monitoring. Ideally, such bioelectronic interfaces should not obstruct the inherent sensations and physiological changes of their hosts. The full life cycle of the interfaces should also be designed to minimize their environmental footprint. Here we report imperceptible augmentation of living systems through in situ tethering of organic bioelectronic fibres. Using an orbital spinning technique, substrate-free and open fibre networks—which are based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate—can be tethered to biological surfaces, including fingertips, chick embryos and plants. We use customizable fibre networks to create on-skin electrodes that can record electrocardiogram and electromyography signals, skin-gated organic electrochemical transistors and augmented touch and plant interfaces. We also show that the fibres can be used to couple prefabricated microelectronics and electronic textiles, and that the fibres can be repaired, upgraded and recycled.
CytoSIP: an annotated structural atlas for interactions involving cytokines or cytokine receptors
Authors: Wang Lu , Sun Fang , Li Qianying , Ma Haojie , Zhong Juanhong , Zhang Huihui , Cheng Siyi , Wu Hao , Zhao Yanmin , Wang Nasui , Xie Zhongqiu , Zhao Mingyi , Zhu Ping , Zheng Heping
Published: May 2024

Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top, facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.
In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance
Authors: Antón-Fernández Alejandro , Roldán-Lázaro Marta , Vallés-Saiz Laura , Ávila Jesús , Hernández Félix
Published: May 2024

In recent years, there has been success in partially reprogramming peripheral organ cells using cyclic Yamanaka transcription factor (YF) expression, resulting in the reversal of age-related pathologies. In the case of the brain, the effects of partial reprogramming are scarcely known, and only some of its effects have been observed through the widespread expression of YF. This study is the first to exclusively partially reprogram a specific subpopulation of neurons in the cerebral cortex of aged mice. The in vivo model demonstrate that YF expression in postmitotic neurons does not dedifferentiate them, and it avoids deleterious effects observed with YF expression in other cell types. Additionally, our study demonstrates that only cyclic, not continuous, expression of YF result in a noteworthy enhancement of cognitive function in adult mice. This enhancement is closely tied to increased neuronal activation in regions related to memory processes, reversed aging-related epigenetic markers and to increased plasticity, induced by the reorganization of the extracellular matrix. These findings support the therapeutic potential of targeted partial reprogramming of neurons in addressing age-associated phenotypes and neurodegenerative diseases correlated with aging.
In vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis
Authors: Wang Baowei , Liu Yang , Bai Xuelian , Tian Huijuan , Wang Lina , Feng Miao , Xia Hairong
Published: May 2024

Generating genetic diversity lies at the heart of directed evolution which has been widely used to engineer genetic parts and gene circuits in synthetic biology. With the ever-expanding application of directed evolution, different approaches of generating genetic diversity are required to enrich the traditional toolbox. Here we show in vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis (epADS). This approach comprises a three-step process which incorporates base errors randomly generated during chemical synthesis of oligonucleotides under specific conditions into the target DNA. Through this method, 200 ~ 4000 folds of diversification in fluorescent strength have been achieved in genes encoding fluorescent proteins. EpADS has also been successfully used to diversify regulatory genetic parts, synthetic gene circuits and even increase microbial tolerance to carbenicillin in a short time period. EpADS would be an alternative tool for directed evolution which may have useful applications in synthetic biology.
Weak neuronal glycolysis sustains cognition and organismal fitness
Authors: Jimenez-Blasco Daniel , Agulla Jesús , Lapresa Rebeca , Garcia-Macia Marina , Bobo-Jimenez Veronica , Garcia-Rodriguez Dario , Manjarres-Raza Israel , Fernandez Emilio , Jeanson Yannick , Khoury Spiro , Portais Jean-Charles , Padro Daniel , Ramos-Cabrer Pedro , Carmeliet Peter , Almeida Angeles , Bolaños Juan P.
Published: May 2024

The energy cost of neuronal activity is mainly sustained by glucose1,2. However, in an apparent paradox, neurons modestly metabolize glucose through glycolysis3–6, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase–fructose-2,6-bisphosphatase-3 (PFKFB3)3,7,8, a key glycolysis-promoting enzyme. To evaluate the in vivo physiological importance of this hypoglycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression. In vivo molecular, biochemical and metabolic flux analyses of these neurons revealed an accumulation of anomalous mitochondria, complex I disassembly, bioenergetic deficiency and mitochondrial redox stress. Notably, glycolysis-mediated nicotinamide adenine dinucleotide (NAD+) reduction impaired sirtuin-dependent autophagy. Furthermore, these mice displayed cognitive decline and a metabolic syndrome that was mimicked by confining Pfkfb3 expression to hypothalamic neurons. Neuron-specific genetic ablation of mitochondrial redox stress or brain NAD+ restoration corrected these behavioural alterations. Thus, the weak glycolytic nature of neurons is required to sustain higher-order organismal functions.
Super phantoms: advanced models for testing medical imaging technologies
Authors: Manohar Srirang , Sechopoulos Ioannis , Anastasio Mark A. , Maier-Hein Lena , Gupta Rajiv
Published: May 2024

Phantoms are test objects used for initial testing and optimization of medical imaging techniques, but these rarely capture the complex properties of the tissue. Here we introduce super phantoms, that surpass standard phantoms being able to replicate complex anatomic and functional imaging properties of tissues and organs. These super phantoms can be computer models, inanimate physical objects, or ex-vivo organs. Testing on these super phantoms, will enable iterative improvements well before in-vivo studies, fostering innovation. We illustrate super phantom examples, address development challenges, and envision centralized facilities supporting multiple institutions in applying these models for medical advancements.
Deliberately ignoring inequality to avoid rejecting unfair offers
Authors: Offer Konstantin , Mischkowski Dorothee , Rahwan Zoe , Engel Christoph
Published: May 2024

Why do people punish experienced unfairness if it induces costs for both the punisher and punished person(s) without any direct material benefits for the punisher? Economic theories of fairness propose that punishers experience disutility from disadvantageous inequality and punish in order to establish equality in outcomes. We tested these theories in a modified Ultimatum Game (N = 1370) by examining whether people avoid the urge to reject unfair offers, and thereby punish the proposer, by deliberately blinding themselves to unfairness. We found that 53% of participants deliberately ignored whether they had received an unfair offer. Among these participants, only 6% of offers were rejected. As expected, participants who actively sought information rejected significantly more unfair offers (39%). Averaging these rejection rates to 21%, no significant difference to the rejection rate by participants who were directly informed about unfairness was found, contrary to our hypothesis. We interpret these findings as evidence for sorting behavior: People who punish experienced unfairness seek information about it, while those who do not punish deliberately ignore it.
Increasing psychopharmacology clinical trial success rates with digital measures and biomarkers: Future methods
Authors: Reiter Jacob E. , Nickels Stefanie , Nelson Benjamin W. , Rainaldi Erin , Peng Lily , Doraiswamy P. Murali , Kapur Ritu , Abernethy Amy , Trister Andrew
Published: May 2024

Psychiatric trials have some of the lowest success rates across therapeutic areas, resulting in decreased investment in psychopharmacological drug development even as the need for more effective treatments grows. Digital measures and digital biomarkers (DBMs) provide one potential avenue for ameliorating three of the largest problems impeding clinical trial success in psychiatry: diagnostic heterogeneity, endpoint subjectivity, and high placebo response rates. First, DBMs may address heterogeneity and comorbidity in psychiatric nosology by identifying predictive DBMs of treatment response via the targeting of drugs to psychiatric subtypes. Second, DBMs can provide objective measures of physiology and behavior that when grounded in meaningful aspects of health (MAH) could support use for regulatory decision-making. By objectively and continuously measuring aspects of a patient’s disease that the patient wants to improve or prevent from getting worse, DBMs might provide clinical trial endpoints that are more sensitive to treatment effects as compared to traditional clinician-reported outcomes. Lastly, DBMs could help address challenges surrounding high placebo response rates. Development of predictive DBMs of placebo response may allow for improved enrichment study designs to reduce placebo response. Objective digital measures may also be more robust against the placebo effect and offer an improved study endpoint alternative. Successful deployment of DBMs to address the historical challenges facing psychiatric drug trials will require close collaboration between industry, academic, and regulatory partners.
Neuraminidase inhibition promotes the collective migration of neurons and recovery of brain function
Authors: Matsumoto Mami , Matsushita Katsuyoshi , Hane Masaya , Wen Chentao , Kurematsu Chihiro , Ota Haruko , Bang Nguyen Huy , Quynh Thai Truc , Herranz-Pérez Vicente , Sawada Masato , Fujimoto Koichi , García-Verdugo José Manuel , Kimura Koutarou D , Seki Tatsunori , Sato Chihiro , Ohno Nobuhiko , Sawamoto Kazunobu
Published: May 2024

In the injured brain, new neurons produced from endogenous neural stem cells form chains and migrate to injured areas and contribute to the regeneration of lost neurons. However, this endogenous regenerative capacity of the brain has not yet been leveraged for the treatment of brain injury. Here, we show that in healthy brain chains of migrating new neurons maintain unexpectedly large non-adherent areas between neighboring cells, allowing for efficient migration. In instances of brain injury, neuraminidase reduces polysialic acid levels, which negatively regulates adhesion, leading to increased cell–cell adhesion and reduced migration efficiency. The administration of zanamivir, a neuraminidase inhibitor used for influenza treatment, promotes neuronal migration toward damaged regions, fosters neuronal regeneration, and facilitates functional recovery. Together, these findings shed light on a new mechanism governing efficient neuronal migration in the adult brain under physiological conditions, pinpoint the disruption of this mechanism during brain injury, and propose a promising therapeutic avenue for brain injury through drug repositioning.
Sedimentation kinetics and stability mechanisms of iron and manganese colloids in simulated groundwater
Authors: Huang Shuxin , Zhang Caixiang , Chen Lu , Xiong Ruihan , Li Jiasen , Xie Jidao , Fan Zenghui , Lv You
Published: May 2024

The occurrence of different forms of iron and manganese colloids in the subsurface environment has been widely reported.
Exploring the molecular structure of lipids in the design of artificial lipidated antifungal proteins
Authors: Saputra Hendra , Safaat Muhammad , Uchida Kazuki , Santoso Pugoh , Wakabayashi Rie , Goto Masahiro , Taira Toki , Kamiya Noriho
Published: May 2024

The antifungal activity of a small chitin-binding domain from antifungal chitinase was enhanced by the artificial lipidation with a specific alkyl chain length and structure in the presence of amphotericin B.
Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing
Authors: Zeng Hui , Zhou Shan , Zhang Xin , Liang Qirui , Yan Miao , Xu Yeqing , Guo Yaxin , Hu Xiaomeng , Jiang Lei , Kong Biao
Published: May 2024

A periodic mesoporous organosilica (PMO)-based heteromembrane with hierarchical pore architecture and glutathione (GSH)-responsive switchable wettability is synthesized for sensitive and efficient GSH detection.
High-quality heteroepitaxy of ε-Ga2O3 films on 4H-SiC substrates grown via MOCVD
Authors: Chen Shujian , Chen Zimin , Chen Weiqu , Fang Paiwen , Lv Zesheng , Cai Bindi , Che Congcong , Liang Jun , Wang Xinzhong , Wang Gang , Pei Yanli
Published: May 2024

High-quality ε-Ga2O3 epitaxial layers were grown on a 4H-SiC substrate via MOCVD. A (004) XRC FWHM of the ε-Ga2O3 epitaxial layer as small as 0.09° (341 arcsec) is achieved.
Molybdenum catalysts based on salan ligands for the deoxydehydration reaction
Authors: Wagner Nathan J. , Tang Wei-Chien , Wagner Jonathan K. , Nguyen Binh T. , Lam Jamie Y. , Gibbons-Stovall Skyler K. , Matias Andrea C. , Martinez Stephenie E. , Trieu-Tran Tristhan , Clabaugh Garrit M. , Navarro Christine A. , Abboud Ibrahim , Flores Francis X. , Nicholas Kenneth M. , John Alex
Published: May 2024

Ligand effects have been evaluated in deoxydehydration (DODH) catalyzed by dioxomolybdenum complexes of salan ligands.
Flexible, model-agnostic method for materials data extraction from text using general purpose language models
Authors: Polak Maciej P. , Modi Shrey , Latosinska Anna , Zhang Jinming , Wang Ching-Wen , Wang Shaonan , Hazra Ayan Deep , Morgan Dane
Published: May 2024

This study presents an efficient language model-based method for high-precision data extraction from text, requiring minimal human effort.
Effects of multifunctional cerium-doped carbon dots on photosynthetic capacity and nutritional quality of lettuce
Authors: Zhao Shili , Li Chen , Wu Caijuan , Hu Juan , Zhang Zhiwei , Lei Bingfu , Li Wei , Hu Chaofan , Liu Yingliang , Zheng Mingtao
Published: May 2024

Cerium-doped carbon dots (Ce-CDs) have been prepared using a one-pot hydrothermal method and employed as a foliar fertilizer, which can improve the nutritional quality of lettuce, and promote the photosynthetic capacity of plants.
Manganese-catalyzed nucleophilic addition of aldehydes to carbonyl compounds via hydrazone umpolung on water
Authors: Salgado Jan Michael , Castillo-Pazos Durbis J. , Lasso Juan D. , Stock Konstantin L. , Li Chao-Jun
Published: May 2024

Herein, we report an operationally simple addition of hydrazones to carbonyl compounds using an earth-abundant metal, under aqueous and aerobic conditions.
Electrochemical direct α-amidation and α-pyrazolation of N-alkoxy- and N-aryloxycarbonyl pyrrolidines
Authors: Wang Zhuang , Liu Yuxiu , Song Hongjian , Wang Qingmin
Published: May 2024

We have developed a straightforward electrochemical protocol for direct α-amidation and α-pyrazolation of N-alkoxy- and N-aryloxycarbonyl pyrrolidines with amides or pyrazoles.
Novel approach to enhancing the anticancer efficacy of methyl jasmonate with PEG-incorporated cationic polymers
Authors: Kumar Nishant , Singh Pratibha , Zhao Dandan , Rajan Robin , Matsumura Kazuaki
Published: May 2024

A series of PEG-based copolymers was synthesised and tested across various cancer cell lines, the polymers exhibit marked anticancer efficacy and notable selectivity towards normal cell lines, underscoring their potential as anticancer agents.
Targeted suppression of oral squamous cell carcinoma by pyrimidine-tethered quinoxaline derivatives
Authors: Choithramani Asmita , Das Rudradip , Bothra Gourav , Patel Vatsa Priyanka , Muthukumar Venkatesh , Bhuvana Bombothu Kavya Sai , Kapoor Saumya , Moola Deepshika , Chowdhury Moumita Ghosh , Mandoli Amit , Shard Amit
Published: May 2024

Oral cancer (OC) stands as a prominent cause of global mortality.
Identification of lysosomotropism using explainable machine learning and morphological profiling cell painting data
Authors: Tandon Aishvarya , Santura Anna , Waldmann Herbert , Pahl Axel , Czodrowski Paul
Published: May 2024

Explainable ML was used to identify important chemical structural properties that contribute to lysosomotropism.
Supramolecular assembly of multifunctional protein gels via an N-glycosylation consensus sequence fusion domain
Authors: Hill Eric D. , Michel Stephen , Sequeira Natasha R. , Keselowsky Benjamin G. , Hudalla Gregory A.
Published: May 2024

Stimuli-responsive polypeptide tags direct the assembly of active proteins into supramolecular assemblies. This allows for recombinant expression of soluble fusion protein and subsequent user-controlled formation of functional biomaterials.
Advancements in nanomaterials for nanosensors: a comprehensive review
Authors: Darwish Moustafa A. , Abd-Elaziem Walaa , Elsheikh Ammar , Zayed Abdelhameed A.
Published: May 2024

Nanomaterials (NMs) exhibit unique properties that render them highly suitable for developing sensitive and selective nanosensors across various domains.
Microneedle-assisted transdermal delivery of carvedilol nanosuspension for the treatment of hypertension
Authors: Deshpande Anushri , Mer Vidhi , Patel Darshana , Thakkar Hetal
Published: May 2024

Carvedilol nanosuspension loaded microneedles patch was formulated and characterized by particle size, zeta potential, solubility, Transmission Electron Microscopy, X-Ray Diffraction, in-vitro release and in-vivo pharmacokinetic studies