bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell facilitation promotes growth and survival under drug pressure in breast cancer
Authors: Emond Rena , Griffiths Jason I. , Grolmusz Vince Kornél , Nath Aritro , Chen Jinfeng , Medina Eric F. , Sousa Rachel S. , Synold Timothy , Adler Frederick R. , Bild Andrea H.
Published: June 2023

The interplay of positive and negative interactions between drug-sensitive and resistant cells influences the effectiveness of treatment in heterogeneous cancer cell populations. Here, we study interactions between estrogen receptor-positive breast cancer cell lineages that are sensitive and resistant to ribociclib-induced cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition. In mono- and coculture, we find that sensitive cells grow and compete more effectively in the absence of treatment. During treatment with ribociclib, sensitive cells survive and proliferate better when grown together with resistant cells than when grown in monoculture, termed facilitation in ecology. Molecular, protein, and genomic analyses show that resistant cells increase metabolism and production of estradiol, a highly active estrogen metabolite, and increase estrogen signaling in sensitive cells to promote facilitation in coculture. Adding estradiol in monoculture provides sensitive cells with increased resistance to therapy and cancels facilitation in coculture. Under partial inhibition of estrogen signaling through low-dose endocrine therapy, estradiol supplied by resistant cells facilitates sensitive cell growth. However, a more complete blockade of estrogen signaling, through higher-dose endocrine therapy, diminished the facilitative growth of sensitive cells. Mathematical modeling quantifies the strength of competition and facilitation during CDK4/6 inhibition and predicts that blocking facilitation has the potential to control both resistant and sensitive cancer cell populations and inhibit the emergence of a refractory population during cell cycle therapy.
Predictive neural representations of naturalistic dynamic input
Authors: de Vries Ingmar E. J. , Wurm Moritz F.
Published: June 2023

Adaptive behavior such as social interaction requires our brain to predict unfolding external dynamics. While theories assume such dynamic prediction, empirical evidence is limited to static snapshots and indirect consequences of predictions. We present a dynamic extension to representational similarity analysis that uses temporally variable models to capture neural representations of unfolding events. We applied this approach to source-reconstructed magnetoencephalography (MEG) data of healthy human subjects and demonstrate both lagged and predictive neural representations of observed actions. Predictive representations exhibit a hierarchical pattern, such that high-level abstract stimulus features are predicted earlier in time, while low-level visual features are predicted closer in time to the actual sensory input. By quantifying the temporal forecast window of the brain, this approach allows investigating predictive processing of our dynamic world. It can be applied to other naturalistic stimuli (e.g., film, soundscapes, music, motor planning/execution, social interaction) and any biosignal with high temporal resolution.
A selective autophagy receptor VISP1 induces symptom recovery by targeting viral silencing suppressors
Authors: Tong Xin , Zhao Jia-Jia , Feng Ya-Lan , Zou Jing-Ze , Ye Jian , Liu Junfeng , Han Chenggui , Li Dawei , Wang Xian-Bing
Published: June 2023

Selective autophagy is a double-edged sword in antiviral immunity and regulated by various autophagy receptors. However, it remains unclear how to balance the opposite roles by one autophagy receptor. We previously identified a virus-induced small peptide called VISP1 as a selective autophagy receptor that facilitates virus infections by targeting components of antiviral RNA silencing. However, we show here that VISP1 can also inhibit virus infections by mediating autophagic degradation of viral suppressors of RNA silencing (VSRs). VISP1 targets the cucumber mosaic virus (CMV) 2b protein for degradation and attenuates its suppression activity on RNA silencing. Knockout and overexpression of VISP1 exhibit compromised and enhanced resistance against late infection of CMV, respectively. Consequently, VISP1 induces symptom recovery from CMV infection by triggering 2b turnover. VISP1 also targets the C2/AC2 VSRs of two geminiviruses and enhances antiviral immunity. Together, VISP1 induces symptom recovery from severe infections of plant viruses through controlling VSR accumulation.
The proteomic landscape of soft tissue sarcomas
Authors: Burns Jessica , Wilding Christopher P. , Krasny Lukas , Zhu Xixuan , Chadha Madhumeeta , Tam Yuen Bun , PS Hari , Mahalingam Aswanth H. , Lee Alexander T. J. , Arthur Amani , Guljar Nafia , Perkins Emma , Pankova Valeriya , Jenks Andrew , Djabatey Vanessa , Szecsei Cornelia , McCarthy Frank , Ragulan Chanthirika , Milighetti Martina , Roumeliotis Theodoros I. , Crosier Stephen , Finetti Martina , Choudhary Jyoti S. , Judson Ian , Fisher Cyril , Schuster Eugene F. , Sadanandam Anguraj , Chen Tom W. , Williamson Daniel , Thway Khin , Jones Robin L. , Cheang Maggie C. U. , Huang Paul H.
Published: June 2023

Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of tumour specimens from 321 STS patients representing 11 histological subtypes. Within leiomyosarcomas, we identify three proteomic subtypes with distinct myogenesis and immune features, anatomical site distribution and survival outcomes. Characterisation of undifferentiated pleomorphic sarcomas and dedifferentiated liposarcomas with low infiltrating CD3 + T-lymphocyte levels nominates the complement cascade as a candidate immunotherapeutic target. Comparative analysis of proteomic and transcriptomic profiles highlights the proteomic-specific features for optimal risk stratification in angiosarcomas. Finally, we define functional signatures termed Sarcoma Proteomic Modules which transcend histological subtype classification and show that a vesicle transport protein signature is an independent prognostic factor for distant metastasis. Our study highlights the utility of proteomics for identifying molecular subgroups with implications for risk stratification and therapy selection and provides a rich resource for future sarcoma research.
Learning in a sensory cortical microstimulation task is associated with elevated representational stability
Authors: Pancholi Ravi , Ryan Lauren , Peron Simon
Published: June 2023

Sensory cortical representations can be highly dynamic, raising the question of how representational stability impacts learning. We train mice to discriminate the number of photostimulation pulses delivered to opsin-expressing pyramidal neurons in layer 2/3 of primary vibrissal somatosensory cortex. We simultaneously track evoked neural activity across learning using volumetric two-photon calcium imaging. In well-trained animals, trial-to-trial fluctuations in the amount of photostimulus-evoked activity predicted animal choice. Population activity levels declined rapidly across training, with the most active neurons showing the largest declines in responsiveness. Mice learned at varied rates, with some failing to learn the task in the time provided. The photoresponsive population showed greater instability both within and across behavioral sessions among animals that failed to learn. Animals that failed to learn also exhibited a faster deterioration in stimulus decoding. Thus, greater stability in the stimulus response is associated with learning in a sensory cortical microstimulation task.
Sequence variants affecting the genome-wide rate of germline microsatellite mutations
Authors: Kristmundsdottir Snaedis , Jonsson Hakon , Hardarson Marteinn T. , Palsson Gunnar , Beyter Doruk , Eggertsson Hannes P. , Gylfason Arnaldur , Sveinbjornsson Gardar , Holley Guillaume , Stefansson Olafur A. , Halldorsson Gisli H. , Olafsson Sigurgeir , Arnadottir Gudny. A. , Olason Pall I. , Eiriksson Ogmundur , Masson Gisli , Thorsteinsdottir Unnur , Rafnar Thorunn , Sulem Patrick , Helgason Agnar , Gudbjartsson Daniel F. , Halldorsson Bjarni V. , Stefansson Kari
Published: June 2023

Microsatellites are polymorphic tracts of short tandem repeats with one to six base-pair (bp) motifs and are some of the most polymorphic variants in the genome. Using 6084 Icelandic parent-offspring trios we estimate 63.7 (95% CI: 61.9–65.4) microsatellite de novo mutations (mDNMs) per offspring per generation, excluding one bp repeats motifs (homopolymers) the estimate is 48.2 mDNMs (95% CI: 46.7–49.6). Paternal mDNMs occur at longer repeats than maternal ones, which are in turn larger with a mean size of 3.4 bp vs 3.1 bp for paternal ones. mDNMs increase by 0.97 (95% CI: 0.90–1.04) and 0.31 (95% CI: 0.25–0.37) per year of father’s and mother’s age at conception, respectively. Here, we find two independent coding variants that associate with the number of mDNMs transmitted to offspring; The minor allele of a missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.
Single cell Hi-C identifies plastic chromosome conformations underlying the gastrulation enhancer landscape
Authors: Rappoport Nimrod , Chomsky Elad , Nagano Takashi , Seibert Charlie , Lubling Yaniv , Baran Yael , Lifshitz Aviezer , Leung Wing , Mukamel Zohar , Shamir Ron , Fraser Peter , Tanay Amos
Published: June 2023

Embryonic development involves massive proliferation and differentiation of cell lineages. This must be supported by chromosome replication and epigenetic reprogramming, but how proliferation and cell fate acquisition are balanced in this process is not well understood. Here we use single cell Hi-C to map chromosomal conformations in post-gastrulation mouse embryo cells and study their distributions and correlations with matching embryonic transcriptional atlases. We find that embryonic chromosomes show a remarkably strong cell cycle signature. Despite that, replication timing, chromosome compartment structure, topological associated domains (TADs) and promoter-enhancer contacts are shown to be variable between distinct epigenetic states. About 10% of the nuclei are identified as primitive erythrocytes, showing exceptionally compact and organized compartment structure. The remaining cells are broadly associated with ectoderm and mesoderm identities, showing only mild differentiation of TADs and compartment structures, but more specific localized contacts in hundreds of ectoderm and mesoderm promoter-enhancer pairs. The data suggest that while fully committed embryonic lineages can rapidly acquire specific chromosomal conformations, most embryonic cells are showing plastic signatures driven by complex and intermixed enhancer landscapes.
Lattice oxygen-mediated electron tuning promotes electrochemical hydrogenation of acetonitrile on copper catalysts
Authors: Wei Cong , Fang Yanyan , Liu Bo , Tang Chongyang , Dong Bin , Yin Xuanwei , Bian Zenan , Wang Zhandong , Liu Jun , Qian Yitai , Wang Gongming
Published: June 2023

Copper is well-known to be selective to primary amines via electrocatalytic nitriles hydrogenation. However, the correlation between the local fine structure and catalytic selectivity is still illusive. Herein, we find that residual lattice oxygen in oxide-derived Cu nanowires (OD-Cu NWs) plays vital roles in boosting the acetonitrile electroreduction efficiency. Especially at high current densities of more than 1.0 A cm−2, OD-Cu NWs exhibit relatively high Faradic efficiency. Meanwhile, a series of advanced in situ characterizations and theoretical calculations uncover that oxygen residues, in the form of Cu4-O configuration, act as electron acceptors to confine the free electron flow on the Cu surface, consequently improving the kinetics of nitriles hydrogenation catalysis. This work could provide new opportunities to further improve the hydrogenation performance of nitriles and beyond, by employing lattice oxygen-mediated electron tuning engineering.
Inhibition of chitin deacetylases to attenuate plant fungal diseases
Authors: Liu Lin , Xia Yeqiang , Li Yingchen , Zhou Yong , Su Xiaofeng , Yan Xiaojing , Wang Yan , Liu Wende , Cheng Hongmei , Wang Yuanchao , Yang Qing
Published: June 2023

Phytopathogenic fungi secrete chitin deacetylase (CDA) to escape the host’s immunological defense during infection. Here, we showed that the deacetylation activity of CDA toward chitin is essential for fungal virulence. Five crystal structures of two representative and phylogenetically distant phytopathogenic fungal CDAs, VdPDA1 from Verticillium dahliae and Pst_13661 from Puccinia striiformis f. sp. tritici, were obtained in ligand-free and inhibitor-bound forms. These structures suggested that both CDAs have an identical substrate-binding pocket and an Asp-His-His triad for coordinating a transition metal ion. Based on the structural identities, four compounds with a benzohydroxamic acid (BHA) moiety were obtained as phytopathogenic fungal CDA inhibitors. BHA exhibited high effectiveness in attenuating fungal diseases in wheat, soybean, and cotton. Our findings revealed that phytopathogenic fungal CDAs share common structural features, and provided BHA as a lead compound for the design of CDA inhibitors aimed at attenuating crop fungal diseases.
The intersection of the retrieval state and internal attention
Authors: Long Nicole M.
Published: June 2023

Large-scale brain states or distributed patterns of brain activity modulate downstream processing and behavior. Sustained attention and memory retrieval states impact subsequent memory, yet how these states relate to one another is unclear. I hypothesize that internal attention is a central process of the retrieval state. The alternative is that the retrieval state specifically reflects a controlled, episodic retrieval mode, engaged only when intentionally accessing events situated within a spatiotemporal context. To test my hypothesis, I developed a mnemonic state classifier independently trained to measure retrieval state evidence and applied this classifier to a spatial attention task. I find that retrieval state evidence increases during delay and response intervals when participants are maintaining spatial information. Critically, retrieval state evidence is positively related to the amount of maintained spatial location information and predicts target detection reaction times. Together, these findings support the hypothesis that internal attention is a central process of the retrieval state.
The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells
Authors: Leoni Cristina , Bataclan Marian , Ito-Kureha Taku , Heissmeyer Vigo , Monticelli Silvia
Published: June 2023

Mast cells are central players in allergy and asthma, and their dysregulated responses lead to reduced quality of life and life-threatening conditions such as anaphylaxis. The RNA modification N6-methyladenosine (m6A) has a prominent impact on immune cell functions, but its role in mast cells remains unexplored. Here, by optimizing tools to genetically manipulate primary mast cells, we reveal that the m6A mRNA methyltransferase complex modulates mast cell proliferation and survival. Depletion of the catalytic component Mettl3 exacerbates effector functions in response to IgE and antigen complexes, both in vitro and in vivo. Mechanistically, deletion of Mettl3 or Mettl14, another component of the methyltransferase complex, lead to the enhanced expression of inflammatory cytokines. By focusing on one of the most affected mRNAs, namely the one encoding the cytokine IL-13, we find that it is methylated in activated mast cells, and that Mettl3 affects its transcript stability in an enzymatic activity-dependent manner, requiring consensus m6A sites in the Il13 3’-untranslated region. Overall, we reveal that the m6A machinery is essential in mast cells to sustain growth and to restrain inflammatory responses.
Hierarchical conductive metal-organic framework films enabling efficient interfacial mass transfer
Authors: Huang Chuanhui , Shang Xinglong , Zhou Xinyuan , Zhang Zhe , Huang Xing , Lu Yang , Wang Mingchao , Löffler Markus , Liao Zhongquan , Qi Haoyuan , Kaiser Ute , Schwarz Dana , Fery Andreas , Wang Tie , Mannsfeld Stefan C. B. , Hu Guoqing , Feng Xinliang , Dong Renhao
Published: June 2023

Heterogeneous reactions associated with porous solid films are ubiquitous and play an important role in both nature and industrial processes. However, due to the no-slip boundary condition in pressure-driven flows, the interfacial mass transfer between the porous solid surface and the environment is largely limited to slow molecular diffusion, which severely hinders the enhancement of heterogeneous reaction kinetics. Herein, we report a hierarchical-structure-accelerated interfacial dynamic strategy to improve interfacial gas transfer on hierarchical conductive metal-organic framework (c-MOF) films. Hierarchicalc-MOF films are synthesized via the in-situ transformation of insulating MOF film precursors usingπ-conjugated ligands and comprise both a nanoporous shell and hollow inner voids. The introduction of hollow structures in thec-MOF films enables an increase of gas permeability, thus enhancing the motion velocity of gas molecules toward thec-MOF film surface, which is more than 8.0-fold higher than that of bulk-type film. Thec-MOF film-based chemiresistive sensor exhibits a faster response towards ammonia than other reported chemiresistive ammonia sensors at room temperature and a response speed 10 times faster than that of the bulk-type film.
Interpretable discovery of semiconductors with machine learning
Authors: Choubisa Hitarth , Todorović Petar , Pina Joao M. , Parmar Darshan H. , Li Ziliang , Voznyy Oleksandr , Tamblyn Isaac , Sargent Edward H.
Published: June 2023

Machine learning models of material properties accelerate materials discovery, reproducing density functional theory calculated results at a fraction of the cost1–6. To bridge the gap between theory and experiments, machine learning predictions need to be distilled in the form of interpretable chemical rules that can be used by experimentalists. Here we develop a framework to address this gap by combining evolutionary algorithm-powered search with machine-learning surrogate models. We then couple the search results with supervised learning and statistical testing. This strategy enables the efficient search of a materials space while providing interpretable design rules. We demonstrate its effectiveness by developing rules for the design of direct bandgap materials, stable UV emitters, and IR perovskite emitters. Finally, we conclusively show how DARWIN-generated rules are statistically more robust and applicable to a wide range of applications including the design of UV halide perovskites.
Optimal measurement structures for contextuality applications
Authors: Liu Yuan , Ramanathan Ravishankar , Horodecki Karol , Rosicka Monika , Horodecki Paweł
Published: June 2023

The Kochen-Specker (KS) theorem is a cornerstone result in the foundations of quantum mechanics describing the fundamental difference between quantum theory and classical non-contextual theories. Recently specific substructures termed 01-gadgets were shown to exist within KS proofs that capture the essential contradiction of the theorem. Here, we show these gadgets and their generalizations provide an optimal toolbox for contextuality applications including (i) constructing classical channels exhibiting entanglement-assisted advantage in zero-error communication, (ii) identifying large separations between quantum theory and binary generalized probabilistic theories, and (iii) finding optimal tests for contextuality-based semi-device-independent randomness generation. Furthermore, we introduce and study a generalization to definite prediction sets for more general logical propositions, that we term higher-order gadgets. We pinpoint the role these higher-order gadgets play in KS proofs by identifying these as induced subgraphs within KS graphs and showing how to construct proofs of state-independent contextuality using higher-order gadgets as building blocks. The constructions developed here may help in solving some of the remaining open problems regarding minimal proofs of the Kochen-Specker theorem.
Massively scalable Kerr comb-driven silicon photonic link
Authors: Rizzo Anthony , Novick Asher , Gopal Vignesh , Kim Bok Young , Ji Xingchen , Daudlin Stuart , Okawachi Yoshitomo , Cheng Qixiang , Lipson Michal , Gaeta Alexander L. , Bergman Keren
Published: June 2023

The growth of computing needs for artificial intelligence and machine learning is critically challenging data communications in today’s data-centre systems. Data movement, dominated by energy costs and limited ‘chip-escape’ bandwidth densities, is perhaps the singular factor determining the scalability of future systems. Using light to send information between compute nodes in such systems can dramatically increase the available bandwidth while simultaneously decreasing energy consumption. Through wavelength-division multiplexing with chip-based microresonator Kerr frequency combs, independent information channels can be encoded onto many distinct colours of light in the same optical fibre for massively parallel data transmission with low energy. Although previous high-bandwidth demonstrations have relied on benchtop equipment for filtering and modulating Kerr comb wavelength channels, data-centre interconnects require a compact on-chip form factor for these operations. Here we demonstrate a massively scalable chip-based silicon photonic data link using a Kerr comb source enabled by a new link architecture and experimentally show aggregate single-fibre data transmission of 512 Gb s−1 across 32 independent wavelength channels. The demonstrated architecture is fundamentally scalable to hundreds of wavelength channels, enabling massively parallel terabit-scale optical interconnects for future green hyperscale data centres.
Photonic radar for contactless vital sign detection
Authors: Zhang Ziqian , Liu Yang , Stephens Tegan , Eggleton Benjamin J.
Published: June 2023

Vital sign detection is used across ubiquitous scenarios in medical and health settings, and contact and wearable sensors have been widely deployed. However, they are unsuitable for patients with burn wounds or infants with insufficient areas for attachment. Contactless detection can be achieved using camera imaging, but it is susceptible to ambient light conditions and has privacy concerns. Here we report a photonic radar for non-contact vital sign detection to overcome these challenges. This photonic radar can achieve millimetre-level range resolution based on synthesized radar signals with a bandwidth of up to 30 GHz. The high resolution of the radar system enables accurate respiratory detection from breathing simulators and a cane toad as a human proxy. Moreover, we demonstrate that the optical signals generated from the proposed system can enable vital sign detection based on light detection and ranging (LiDAR). This demonstration reveals the potential of a sensor-fusion architecture that can combine the complementary features of radar and LiDAR to achieve improved sensing accuracy and system resilience. The work provides a technical basis for contactless and high-resolution vital sign detection to meet the increasing demands of future medical and healthcare applications.
Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID
Authors: Bernardini Andrea , Mukherjee Pooja , Scheer Elisabeth , Kamenova Ivanka , Antonova Simona , Mendoza Sanchez Paulina Karen , Yayli Gizem , Morlet Bastien , Timmers H.T. Marc , Tora László
Published: June 2023

Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunit basal transcription factor TFIID nucleates the RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation (RIP) experiments, single-molecule imaging, proteomics and structure–function analyses, we show that human TFIID biogenesis occurs co-translationally. We discovered that all protein heterodimerization steps happen during protein synthesis. We identify TAF1—the largest protein in the complex—as a critical factor for TFIID assembly. TAF1 acts as a flexible scaffold that drives the co-translational recruitment of TFIID submodules preassembled in the cytoplasm. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly of the complex onto the nascent TAF1 polypeptide. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.
A nationwide collapse of a priority grassland bird related to livestock conversion and intensification
Authors: Silva João Paulo , Marques Ana Teresa , Carrapato Carlos , Machado Rui , Alcazar Rita , Delgado Ana , Godinho Carlos , Elias Gonçalo , Gameiro João
Published: June 2023

Grassland birds are among the most threatened and fastest declining terrestrial vertebrate species in Europe, principally due to agricultural intensification and transformation. The little bustard is a priority grassland bird under the European Directive (2009/147/CE) that led to the classification of a network of Special Protected Areas (SPAs) in Portugal. A third national survey carried out in 2022 reveals a worsening of an ongoing population collapse at a national scale. The population declined by 77% and 56% compared to the previous surveys in 2006 and 2016, respectively. We found that the little bustard has greatly disappeared outside SPAs, while the remaining breeding population concentrated within the protected area network is showing a steep decline at a rate of 9% a year. This decline is now twice as fast when compared to the period 2006–2016. Analysis of the variation of the breeding densities between 2006 and 2022 at 49 survey sites revealed that those that initially had higher bustard densities and shifted toward a higher proportion of cattle among the total stocking rate experienced steeper declines. Areas where the density of roads increased also experienced declines over the course of the study period. Agricultural areas converted to or dominated by beef production likely relate to low breeding success and mortality of nesting females in fodder crops. Still, major habitat conversion outside SPAs to permanent crops led to overall habitat destruction, which contributed to the species decline and range contraction. Other threats are likely acting synergistically such as fragmentation, climate change and anthropogenic mortality. The extinction of the little bustard in Portugal is expected in the short term if no conservation actions are put in place.
Divalent cations in human liver pyruvate kinase exemplify the combined effects of complex-equilibrium and allosteric regulation
Authors: Martin Tyler A. , Fenton Aron W.
Published: June 2023

There is growing recognition that the functional outcome of binding of an allosteric regulator to a protein/enzyme is influenced by the presence of other ligands. Here, this complexity is exemplified in the allosteric regulation of human liver pyruvate kinase (hLPYK) that is influenced by the presence of a range of divalent cation types and concentrations. For this system, fructose-1,6-bisphosphate (activator) and alanine (inhibitor) both influence the protein’s affinity for the substrate, phosphoenolpyruvate (PEP). Mg2+, Mn2+, Ni2+, and Co2+ were the primary divalent cations evaluated, although Zn2+, Cd2+, V2+, Pb2+, Fe2+, and Cu2+also supported activity. Allosteric coupling between Fru-1,6-BP and PEP and between Ala and PEP varied depending on divalent cation type and concentration. Due to complicating interactions among small molecules, we did not attempt the fitting of response trends and instead we discuss a range of potential mechanisms that may explain those observed trends. Specifically, observed “substrate inhibition” may result from substrate A in one active site acting as an allosteric regulator for the affinity for substrate B in a second active site of a multimer. We also discuss apparent changes in allosteric coupling that can result from a sub-saturating concentration of a third allosteric ligand.
Effect of sub-dermal exposure of silver nanoparticles on hepatic, renal and cardiac functions accompanying oxidative damage in male Wistar rats
Authors: Olugbodi Janet Olayemi , Lawal Bashir , Bako Godiya , Onikanni Amos Sunday , Abolenin Sulama M. , Mohammud Soliman S. , Ataya Farid S. , Batiha Gaber El-Saber
Published: June 2023

Silver nanoparticles (AgNPs) have been generally used due to their strong antibacterial, antiviral and antifungal and antimicrobial properties. However, their toxicity is a subject of sustained debate, thus requiring further studies. Hence, this study examines the adverse effects of the sub-dermal administered dose of AgNPs (200 nm) on the liver, kidney and heart of male Wistar rats. Thirty male rats were randomly distributed into six groups of five animals per group. Group A and D served as the control and received distilled water for 14 and 28 days respectively. Groups B and C were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 14 days while E and F were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 28 days. The liver, kidney and heart of the animals were collected, processed and used for biochemical and histological analysis. Our results revealed that the subdermal administration of AgNPs induced significant increased (p < 0.05) activities of aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), urea, creatinine, and malondialdehyde (MDA) while decreasing the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total thiol groups in the rat tissues. Our findings suggest that the subdermal administration of AgNPs induced oxidative stress and impaired the hepatic, renal and cardiac functions of male Wistar rats.
Measuring real-time cognitive engagement in remote audiences
Authors: Levordashka Ana , Stanton Fraser Danaë , Gilchrist Iain D.
Published: June 2023

Responses to arts and entertainment media offer a valuable window into human behaviour. Many individuals worldwide spend the vast majority of their leisure time engaging with video content at home. However, there are few ways to study engagement and attention in this natural home viewing context. We used motion-tracking of the head via a web-camera to measure real-time cognitive engagement in 132 individuals while they watched 30 min of streamed theatre content at home. Head movement was negatively associated with engagement across a constellation of measures. Individuals who moved less reported feeling more engaged and immersed, evaluated the performance as more engaging, and were more likely to express interest in watching further. Our results demonstrate the value of in-home remote motion tracking as a low-cost, scalable metric of cognitive engagement, which can be used to collect audience behaviour data in a natural setting.
Feasibility of using intermittent active monitoring of vital signs by smartphone users to predict SARS-CoV-2 PCR positivity
Authors: Dolezalova Nikola , Gkrania-Klotsas Effrossyni , Morelli Davide , Moore Alex , Cunningham Adam C. , Booth Adam , Plans David , Reed Angus B. , Aral Mert , Rennie Kirsten L. , Wareham Nicholas J.
Published: June 2023

Early detection of highly infectious respiratory diseases, such as COVID-19, can help curb their transmission. Consequently, there is demand for easy-to-use population-based screening tools, such as mobile health applications. Here, we describe a proof-of-concept development of a machine learning classifier for the prediction of a symptomatic respiratory disease, such as COVID-19, using smartphone-collected vital sign measurements. The Fenland App study followed 2199 UK participants that provided measurements of blood oxygen saturation, body temperature, and resting heart rate. Total of 77 positive and 6339 negative SARS-CoV-2 PCR tests were recorded. An optimal classifier to identify these positive cases was selected using an automated hyperparameter optimisation. The optimised model achieved an ROC AUC of 0.695 ± 0.045. The data collection window for determining each participant’s vital sign baseline was increased from 4 to 8 or 12 weeks with no significant difference in model performance (F(2) = 0.80, p = 0.472). We demonstrate that 4 weeks of intermittently collected vital sign measurements could be used to predict SARS-CoV-2 PCR positivity, with applicability to other diseases causing similar vital sign changes. This is the first example of an accessible, smartphone-based remote monitoring tool deployable in a public health setting to screen for potential infections.
SpineTool is an open-source software for analysis of morphology of dendritic spines
Authors: Pchitskaya Ekaterina , Vasiliev Peter , Smirnova Daria , Chukanov Vyacheslav , Bezprozvanny Ilya
Published: June 2023

Dendritic spines form most excitatory synaptic inputs in neurons and these spines are altered in many neurodevelopmental and neurodegenerative disorders. Reliable methods to assess and quantify dendritic spines morphology are needed, but most existing methods are subjective and labor intensive. To solve this problem, we developed an open-source software that allows segmentation of dendritic spines from 3D images, extraction of their key morphological features, and their classification and clustering. Instead of commonly used spine descriptors based on numerical metrics we used chord length distribution histogram (CLDH) approach. CLDH method depends on distribution of lengths of chords randomly generated within dendritic spines volume. To achieve less biased analysis, we developed a classification procedure that uses machine-learning algorithm based on experts’ consensus and machine-guided clustering tool. These approaches to unbiased and automated measurements, classification and clustering of synaptic spines that we developed should provide a useful resource for a variety of neuroscience and neurodegenerative research applications.
Modified ulnar lengthening for correction of the Masada type 2 forearm deformity in hereditary multiple exostosis
Authors: Cao Shu , Zeng Jian-Fa , Xiao Sheng , Dong Zhong-Gen , Xu Zi-Li , Liu Hong , Li Xin , Fang Ke , Wen Jie , Zeng Ming , Tang Zhong-Wen , Li Bo , Gong Hao-Li , Li Fan-Ling
Published: June 2023

Few articles have reported on the treatment of Masada type 2 forearm deformities in hereditary multiple exostosis, possibly because of the high redislocation rate and other complications. This study precisely declares the use of modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities. 20 children with Masada type 2 forearm deformities were admitted for surgical treatment at our hospital from February 2014 to February 2021. There were 13 girls and 7 boys, ranging in age from 3.5 to 15 years (mean: 9 years) at the time of operation. We removed the prominent osteochondromas of the distal ulna and the proximal radius, positioned a classic Ilizarov external fixator on the forearm and then performed ulnar transverse one-third proximal diaphyseal subperiosteal osteotomy. We adopted modified ulnar lengthening postoperatively. The effects of surgical correction of deformity and functional improvement of the limb were assessed via regular follow-up and X-ray. The patients were followed up for 36 months, and the ulna was lengthened 26.99 mm on average; all radial heads remained relocated. The radiographic evaluations, including relative ulnar shortening, radial articular angle, and carpal slip, were improved. The functions of the elbow and forearm were all improved after surgery. Modified ulnar lengthening by an Ilizarov external fixation with tumour excision for the treatment of Masada type 2 forearm deformities in hereditary multiple exostoses has been proven to be an effective and reliable technique in the early stage.
Novel gain-tuning for sliding mode control of second-order mechanical systems: theory and experiments
Authors: Xuan-Mung Nguyen , Nguyen Ngoc Phi , Pham Dinh Ba , Dao Nhu-Ngoc , Nguyen Huu Tiep , Ha Le Nhu Ngoc Thanh , Vu Mai The , Hong Sung Kyung
Published: June 2023

The sliding mode control is well-known as a useful control technique that can be applied in several real-world applications. However, a straightforward and efficient process of selecting the sliding mode control gains remains a challenging but interesting topic. This paper investigates a novel gain tuning method for the sliding mode control of second-order mechanical systems. Firstly, we obtain relations between the gains and the natural and damping ratio of the closed-loop system. Secondly, the time constant of the system’s actuators and the system response performance criteria, including settling time and delay time, are taken into consideration to determine appropriate ranges of the gains. These gain ranges allow control designers to select the controller gains in a time-saving manner and ensure that the desired system performance is met and the actuators work properly. Finally, the proposed method is applied to the gain tuning process of a sliding mode altitude controller for an actual quadcopter unmanned aerial vehicle. Simulation and experimental results demonstrate the applicability and effectiveness of this method.
Sickness absence transitions among Swedish twins with back, neck or shoulder pain and common mental disorders applying a multi-state approach
Authors: Kärkkäinen Sanna , Bergström Jakob , Ropponen Annina , Wang Mo , Narusyte Jurgita , Svedberg Pia
Published: June 2023

We aimed to investigate transitions to and from sickness absence, or disability pension among individuals with back, neck, or shoulder pain and/or with common mental disorders (CMDs), and the role of familial (genetics and shared environment) influences on the transitions. Swedish twins born 1935–1985 who responded to pain and CMDs survey items (N = 41,516) were followed on average 8.7 years for sickness absence states in national registers. Multi-state Cox regression models were applied for three exposure groups: pain, CMDs, and presence of both, compared to unexposed. Exposure discordant twin pairs, stratified by zygosity, were analysed to assess the role of familial factors. Hazard Ratios (HR) with 95% confidence intervals and transition intensities were calculated. HRs were similar for transitions between states among those with pain or CMDs. The highest HRs were for transitions from entry to sickness absence and sickness absence to disability pension among those with both pain and CMDs (HRs: 1.61 and 1.43, respectively). Higher HRs for dizygotic compared to monozygotic twins for the first transition to sickness absence and for altering back to not being sickness absent indicate familial confounding. Back, neck, or shoulder pain and/or CMDs indicate a higher risk to become sickness absent and for repeated sickness absence episodes over time compared to unaffected.
The aversive bystander effect whereby egalitarian bystanders overestimate the confrontation of prejudice
Authors: Szekeres Hanna , Halperin Eran , Kende Anna , Saguy Tamar
Published: June 2023

Everyday expression of prejudice continues to pose a social challenge across societies. We tend to assume that to the extent people are egalitarian, they are more likely to confront prejudice—but this might not necessarily be the case. We tested this assumption in two countries (US and Hungary) among majority members of society, using a behavioral paradigm for measuring confronting. Prejudice was directed at various outgroup minority individuals (African Americans, Muslims and Latinos in the US, and Roma in Hungary). Across four experiments (N = 1116), we predicted and found that egalitarian (anti-prejudiced) values were only associated with hypothetical confronting intentions, but not with actual confronting, and stronger egalitarians were more likely to overestimate their confronting than weaker egalitarians—to the point that while intentions differed, the actual confronting rate of stronger and weaker egalitarians were similar. We also predicted and found that such overestimation was associated with internal (and not external) motivation to respond without prejudice. We also identified behavioral uncertainty (being uncertain how to intervene) as a potential explanation for egalitarians’ overestimation. The implications of these findings for egalitarians’ self-reflection, intergroup interventions, and research are discussed.
A refined information processing capacity metric allows an in-depth analysis of memory and nonlinearity trade-offs in neurocomputational systems
Authors: Schulte to Brinke Tobias , Dick Michael , Duarte Renato , Morrison Abigail
Published: June 2023

Since dynamical systems are an integral part of many scientific domains and can be inherently computational, analyses that reveal in detail the functions they compute can provide the basis for far-reaching advances in various disciplines. One metric that enables such analysis is the information processing capacity. This method not only provides us with information about the complexity of a system’s computations in an interpretable form, but also indicates its different processing modes with different requirements on memory and nonlinearity. In this paper, we provide a guideline for adapting the application of this metric to continuous-time systems in general and spiking neural networks in particular. We investigate ways to operate the networks deterministically to prevent the negative effects of randomness on their capacity. Finally, we present a method to remove the restriction to linearly encoded input signals. This allows the separate analysis of components within complex systems, such as areas within large brain models, without the need to adapt their naturally occurring inputs.
Physiology of Saccharomyces cerevisiae during growth on industrial sugar cane molasses can be reproduced in a tailor-made defined synthetic medium
Authors: Eliodório Kevy Pontes , Cunha Gabriel Caetano de Gois e , Lino Felipe Senne de Oliveira , Sommer Morten Otto Alexander , Gombert Andreas Karoly , Giudici Reinaldo , Basso Thiago Olitta
Published: June 2023

Fully defined laboratory media have the advantage of allowing for reproducibility and comparability of results among different laboratories, as well as being suitable for the investigation of how different individual components affect microbial or process performance. We developed a fully defined medium that mimics sugarcane molasses, a frequently used medium in different industrial processes where yeast is cultivated. The medium, named 2SMol, builds upon a previously published semi-defined formulation and is conveniently prepared from some stock solutions: C-source, organic N, inorganic N, organic acids, trace elements, vitamins, Mg + K, and Ca. We validated the 2SMol recipe in a scaled-down sugarcane biorefinery model, comparing the physiology of Saccharomyces cerevisiae in different actual molasses-based media. We demonstrate the flexibility of the medium by investigating the effect of nitrogen availability on the ethanol yield during fermentation. Here we present in detail the development of a fully defined synthetic molasses medium and the physiology of yeast strains in this medium compared to industrial molasses. This tailor-made medium was able to satisfactorily reproduce the physiology of S. cerevisiae in industrial molasses. Thus, we hope the 2SMol formulation will be valuable to researchers both in academia and industry to obtain new insights and developments in industrial yeast biotechnology.
Laboratory investigation of GO-SA-MWCNTs ternary hybrid nanoparticles efficacy on dynamic viscosity and wear properties of oil (5W30) and modeling based on machine learning
Authors: Sepehrnia Mojtaba , Davoodabadi Farahani Somayeh , Hamidi Arani Abolfazl , Taghavi Ali , Golmohammadi Hamidreza
Published: June 2023

In the present study, the properties of ternary hybrid nanofluid (THNF) of oil (5W30) - Graphene Oxide (GO)-Silica Aerogel (SA)-multi-walled carbon nanotubes (MWCNTs) in volume fractions ($$\varphi )$$φ)of 0.3%, 0.6%, 0.9%, 1.2%, and 1.5% and at temperatures 5 to 65 °C has been measured. This THNF is made in a two-step method and a viscometer device made in USA is used for viscosity measurements. The wear test was performed via a pin-on-disk tool according to the ASTM G99 standard. The outcomes show that the viscosity increases with the increase in the$$\varphi$$φ, and the reduction in temperature. By enhancing the temperature by 60 °C, at$$\varphi$$φ= 1.2% and a shear rate (SR) of 50 rpm, a viscosity reduction of approximately 92% has been observed. Also, the results showed that with the rise in SR, the shear stress increased and the viscosity decreased. The estimated values of THNF viscosity at various SRs and temperatures show that its behavior is non-Newtonian. The efficacy of adding nanopowders (NPs) on the stability of the friction and wear behavior of the base oil has been studied. The findings of the test display that the wear rate and friction coefficient increased about 68% and 4.5% for$$\varphi$$φ= 1.5% compared to$$\varphi$$φ= 0. Neural network (NN), Adaptive Neuro-Fuzzy Inference System (ANFIS), and Gaussian process regression (GPR) based on machine learning (ML) have been used to model viscosity. Each model predicted the viscosity of the THNF well, and Rsquare > 0.99.
Cancer associated macrophage-like cells in metastatic renal cell carcinoma predicts for poor prognosis and tracks treatment response in real time
Authors: Ali Amama , Adams Daniel L. , Kasabwala Dimpal M. , Tang Cha-Mei , Ho Thai H.
Published: June 2023

Renal Cell Carcinoma (RCC) is a fatal urological cancer, with one third of patients diagnosed with metastasis, resulting in a 5-year survival of only 12%. Recent advancements in therapies have increased survival in mRCC, but lack efficacy in subtypes, due to treatment resistance and toxic side effects. Currently, white blood cells, hemoglobin, and platelets are limitedly used as blood based biomarkers to help determine RCC prognosis. Cancer associated macrophage-like cells (CAMLs) are a potential mRCC biomarker which have been identified in peripheral blood of patients with malignant tumors and have been shown to predict poor clinical patient outcomes based on their number and size. In this study, blood samples from 40 RCC patients were obtained to evaluate the clinical utility of CAMLs. CAML changes were monitored during treatment regimens to evaluate their ability to predict treatment efficacy. It was observed that patients with smaller CAMLs had better progression free survival (HR = 2.84, 95% CI 1.22–6.60, p = 0.0273) and overall survival (HR = 3.95, 95% CI 1.45–10.78, p = 0.0154) versus patients with larger CAMLs. These findings suggest that CAMLs can be used as a diagnostic, prognostic, and predictive biomarker for patients with RCC which may help improve management of advanced RCC.