bluuebunny/crossref_metadata_2025 huggingface dataset:
WDR5 facilitates recruitment of N-MYC to conserved WDR5 gene targets in neuroblastoma cell lines
Authors: Bumpous Leigh A. , Moe Kylie C. , Wang Jing , Carver Logan A. , Williams Alexandria G. , Romer Alexander S. , Scobee Jesse D. , Maxwell Jack N. , Jones Cheyenne A. , Chung Dai H. , Tansey William P. , Liu Qi , Weissmiller April M.
Published: June 2023

Collectively, the MYC family of oncoprotein transcription factors is overexpressed in more than half of all malignancies. The ability of MYC proteins to access chromatin is fundamental to their role in promoting oncogenic gene expression programs in cancer and this function depends on MYC–cofactor interactions. One such cofactor is the chromatin regulator WDR5, which in models of Burkitt lymphoma facilitates recruitment of the c-MYC protein to chromatin at genes associated with protein synthesis, allowing for tumor progression and maintenance. However, beyond Burkitt lymphoma, it is unknown whether these observations extend to other cancers or MYC family members, and whether WDR5 can be deemed as a “universal” MYC recruiter. Here, we focus on N-MYC amplified neuroblastoma to determine the extent of colocalization between N-MYC and WDR5 on chromatin while also demonstrating that like c-MYC, WDR5 can facilitate the recruitment of N-MYC to conserved WDR5-bound genes. We conclude based on this analysis that N-MYC and WDR5 colocalize invariantly across cell lines at predicted sites of facilitated recruitment associated with protein synthesis genes. Surprisingly, we also identify N-MYC-WDR5 cobound genes that are associated with DNA repair and cell cycle processes. Dissection of chromatin binding characteristics for N-MYC and WDR5 at all cobound genes reveals that sites of facilitated recruitment are inherently different than most N-MYC-WDR5 cobound sites. Our data reveals that WDR5 acts as a universal MYC recruiter at a small cohort of previously identified genes and highlights novel biological functions that may be coregulated by N-MYC and WDR5 to sustain the neuroblastoma state.
Longitudinal study of dietary patterns and hypertension in adults: China Health and Nutrition Survey 1991–2018
Authors: Zhang Jiguo , Du Wenwen , Huang Feifei , Li Li , Bai Jing , Wei Yanli , Wang Zhihong , Zhang Bing , Wang Huijun
Published: June 2023

China is undergoing the nutrition transition that may explain partly the high prevalence of hypertension. We aimed to investigate the longitudinal association between dietary patterns and hypertension in Chinese adults over 28 years of follow-up. We used data collected in the China Health and Nutrition Survey from 1991 to 2018. Adults aged 18 years and above (n = 15,929) were included in the analysis, for whom questionnaires and anthropometric data were collected during at least two waves. Factor analysis was conducted to derive food patterns based on 18 foods or food groups. We constructed three-level mixed-effect linear regression models to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP) in relation to quartiles of dietary pattern score and performed three-level mixed-effect logistic regression models to assess the risk of hypertension. Participants in the top quartile of the modern pattern had a decrease in SBP (β = − 0.51; 95% CI −0.86, −0.16; P < 0.01) when adjusted for all potential confounders, whereas participants in the top quartile of the meat pattern had an increase in DBP (β = 0.31; 95% CI 0.08, 0.53; P < 0.01). Participants in the highest quartile of the meat pattern were more likely to have hypertension (OR = 1.14; 95% CI 1.03, 1.24; P < 0.01). Adherence to the modern pattern characterized by high intake of fruits and dairy products was inversely associated with SBP, whereas the meat pattern was positively associated with DBP and the risk of hypertension. These findings may well have important public health implications.
Neural correlates of hierarchical predictive processes in autistic adults
Authors: Sapey-Triomphe Laurie-Anne , Pattyn Lauren , Weilnhammer Veith , Sterzer Philipp , Wagemans Johan
Published: June 2023

Bayesian theories of autism spectrum disorders (ASD) suggest that atypical predictive mechanisms could underlie the autistic symptomatology, but little is known about their neural correlates. Twenty-six neurotypical (NT) and 26 autistic adults participated in an fMRI study where they performed an associative learning task in a volatile environment. By inverting a model of perceptual inference, we characterized the neural correlates of hierarchically structured predictions and prediction errors in ASD. Behaviorally, the predictive abilities of autistic adults were intact. Neurally, predictions were encoded hierarchically in both NT and ASD participants and biased their percepts. High-level predictions were following activity levels in a set of regions more closely in ASD than NT. Prediction errors yielded activation in shared regions in NT and ASD, but group differences were found in the anterior cingulate cortex and putamen. This study sheds light on the neural specificities of ASD that might underlie atypical predictive processing.
Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3
Authors: Torosyan Hayarpi , Paul Michael D. , Forget Antoine , Lo Megan , Diwanji Devan , Pawłowski Krzysztof , Krogan Nevan J. , Jura Natalia , Verba Kliment A.
Published: June 2023

PEAK pseudokinases are molecular scaffolds which dimerize to regulate cell migration, morphology, and proliferation, as well as cancer progression. The mechanistic role dimerization plays in PEAK scaffolding remains unclear, as there are no structures of PEAKs in complex with their interactors. Here, we report the cryo-EM structure of dimeric PEAK3 in complex with an endogenous 14-3-3 heterodimer. Our structure reveals an asymmetric binding mode between PEAK3 and 14-3-3 stabilized by one pseudokinase domain and the SHED domain of the PEAK3 dimer. The binding interface contains a canonical phosphosite-dependent primary interaction and a unique secondary interaction not observed in previous structures of 14-3-3/client complexes. Additionally, we show that PKD regulates PEAK3/14-3-3 binding, which when prevented leads to PEAK3 nuclear enrichment and distinct protein-protein interactions. Altogether, our data demonstrate that PEAK3 dimerization forms an unusual secondary interface for 14-3-3 binding, facilitating 14-3-3 regulation of PEAK3 localization and interactome diversity.
Collective photothermal bending of flexible organic crystals modified with MXene-polymer multilayers as optical waveguide arrays
Authors: Yang Xuesong , Lan Linfeng , Li Liang , Yu Jinyang , Liu Xiaokong , Tao Ying , Yang Quan-Hong , Naumov Panče , Zhang Hongyu
Published: June 2023

The performance of any engineering material is naturally limited by its structure, and while each material suffers from one or multiple shortcomings when considered for a particular application, these can be potentially circumvented by hybridization with other materials. By combining organic crystals with MXenes as thermal absorbers and charged polymers as adhesive counter-ionic components, we propose a simple access to flexible hybrid organic crystal materials that have the ability to mechanically respond to infrared light. The ensuing hybrid organic crystals are durable, respond fast, and can be cycled between straight and deformed state repeatedly without fatigue. The point of flexure and the curvature of the crystals can be precisely controlled by modulating the position, duration, and power of thermal excitation, and this control can be extended from individual hybrid crystals to motion of ordered two-dimensional arrays of such crystals. We also demonstrate that excitation can be achieved over very long distances (>3 m). The ability to control the shape with infrared light adds to the versatility in the anticipated applications of organic crystals, most immediately in their application as thermally controllable flexible optical waveguides for signal transmission in flexible organic electronics.
400nm ultra-broadband gratings for near-single-cycle 100 Petawatt lasers
Authors: Han Yuxing , Li Zhaoyang , Zhang Yibin , Kong Fanyu , Cao Hongchao , Jin Yunxia , Leng Yuxin , Li Ruxin , Shao Jianda
Published: June 2023

Compressing high-energy laser pulses to a single-cycle and realizing the “λ3 laser concept”, where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750–1150 nm spectral range with a > 90% −1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from −15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100–200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future.
Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein
Authors: Wagner Andreas
Published: June 2023

Can evolvability—the ability to produce adaptive heritable variation—itself evolve through adaptive Darwinian evolution? If so, then Darwinian evolution may help create the conditions that enable Darwinian evolution. Here I propose a framework that is suitable to address this question with available experimental data on adaptive landscapes. I introduce the notion of an evolvability-enhancing mutation, which increases the likelihood that subsequent mutations in an evolving organism, protein, or RNA molecule are adaptive. I search for such mutations in the experimentally characterized and combinatorially complete fitness landscapes of a protein and an RNA molecule. I find that such evolvability-enhancing mutations indeed exist. They constitute a small fraction of all mutations, which shift the distribution of fitness effects of subsequent mutations towards less deleterious mutations, and increase the incidence of beneficial mutations. Evolving populations which experience such mutations can evolve significantly higher fitness. The study of evolvability-enhancing mutations opens many avenues of investigation into the evolution of evolvability.
ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion
Authors: Menolfi Demis , Lee Brian J. , Zhang Hanwen , Jiang Wenxia , Bowen Nicole E. , Wang Yunyue , Zhao Junfei , Holmes Antony , Gershik Steven , Rabadan Raul , Kim Baek , Zha Shan
Published: June 2023

The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in the replication stress response is well defined, the mechanisms by which ATR supports normal cell proliferation remain elusive. Here, we show that ATR is dispensable for the viability of G0-arrested naïve B cells. However, upon cytokine-induced proliferation, Atr-deficient B cells initiate DNA replication efficiently, but by mid-S phase they display dNTP depletion, fork stalling, and replication failure. Nonetheless, productive DNA replication and dNTP levels can be restored in Atr-deficient cells by suppressing origin firing, such as partial inhibition of CDC7 and CDK1 kinase activities. Together, these findings indicate that ATR supports the proliferation of normal unstressed cells by tempering the pace of origin firing during the early S phase to avoid exhaustion of dNTPs and importantly also other replication factors.
Structural basis for DARC binding in reticulocyte invasion by Plasmodium vivax
Authors: Moskovitz Re’em , Pholcharee Tossapol , DonVito Sophia M. , Guloglu Bora , Lowe Edward , Mohring Franziska , Moon Robert W. , Higgins Matthew K.
Published: June 2023

The symptoms of malaria occur during the blood stage of infection, when the parasite replicates within human red blood cells. The human malaria parasite, Plasmodium vivax, selectively invades reticulocytes in a process which requires an interaction between the ectodomain of the human DARC receptor and the Plasmodium vivax Duffy-binding protein, PvDBP. Previous studies have revealed that a small helical peptide from DARC binds to region II of PvDBP (PvDBP-RII). However, it is also known that sulphation of tyrosine residues on DARC affects its binding to PvDBP and these residues were not observed in previous structures. We therefore present the structure of PvDBP-RII bound to sulphated DARC peptide, showing that a sulphate on tyrosine 41 binds to a charged pocket on PvDBP-RII. We use molecular dynamics simulations, affinity measurements and growth-inhibition experiments in parasites to confirm the importance of this interaction. We also reveal the epitope for vaccine-elicited growth-inhibitory antibody DB1. This provides a complete understanding of the binding of PvDBP-RII to DARC and will guide the design of vaccines and therapeutics to target this essential interaction.
Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis
Authors: Lee Ivan T. , Nachbagauer Raffael , Ensz David , Schwartz Howard , Carmona Lizbeth , Schaefers Kristi , Avanesov Andrei , Stadlbauer Daniel , Henry Carole , Chen Ren , Huang Wenmei , Schrempp Daniela Ramirez , Ananworanich Jintanat , Paris Robert
Published: June 2023

Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains. In the active-comparator-controlled Part 2, mRNA-1010 (25 µg, 50 µg, or 100 µg) elicited higher HAI titers than a standard dose, inactivated seasonal influenza vaccine for influenza A strains and comparable HAI titers for influenza B strains. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator. These interim data support continued development of mRNA-1010.
Low power flexible monolayer MoS2 integrated circuits
Authors: Tang Jian , Wang Qinqin , Tian Jinpeng , Li Xiaomei , Li Na , Peng Yalin , Li Xiuzhen , Zhao Yanchong , He Congli , Wu Shuyu , Li Jiawei , Guo Yutuo , Huang Biying , Chu Yanbang , Ji Yiru , Shang Dashan , Du Luojun , Yang Rong , Yang Wei , Bai Xuedong , Shi Dongxia , Zhang Guangyu
Published: June 2023

Monolayer molybdenum disulfide (ML-MoS2) is an emergent two-dimensional (2D) semiconductor holding potential for flexible integrated circuits (ICs). The most important demands for the application of such ML-MoS2 ICs are low power consumption and high performance. However, these are currently challenging to satisfy due to limitations in the material quality and device fabrication technology. In this work, we develop an ultra-thin high-κ dielectric/metal gate fabrication technique for the realization of thin film transistors based on high-quality wafer scale ML-MoS2 on both rigid and flexible substrates. The rigid devices can be operated in the deep-subthreshold regime with low power consumption and show negligible hysteresis, sharp subthreshold slope, high current density, and ultra-low leakage currents. Moreover, we realize fully functional large-scale flexible ICs operating at voltages below 1 V. Our process could represent a key step towards using energy-efficient flexible ML-MoS2 ICs in portable, wearable, and implantable electronics.
Production of high-energy 6-Ah-level Li | |LiNi0.83Co0.11Mn0.06O2 multi-layer pouch cells via negative electrode protective layer coating strategy
Authors: Feng Yangyang , Li Yong , Lin Jing , Wu Huyue , Zhu Lei , Zhang Xiang , Zhang Linlin , Sun Chuan-Fu , Wu Maoxiang , Wang Yaobing
Published: June 2023

Stable lithium metal negative electrodes are desirable to produce high-energy batteries. However, when practical testing conditions are applied, lithium metal is unstable during battery cycling. Here, we propose poly(2-hydroxyethyl acrylate-co-sodium benzenesulfonate) (PHS) as negative electrode protective layer. The PHS contains soft poly (2-hydroxyethyl acrylate) and poly(sodium p-styrene sulfonate), which improve electrode flexibility, connection with the Cu current collector and transport of Li ions. Transmission electron cryomicroscopy measurements reveal that PHS induces the formation of a solid electrolyte interphase with a fluorinated rigid and crystalline internal structure. Furthermore, theoretical calculations suggest that the -SO3- group of poly(sodium p-styrene sulfonate) promotes Li-ion motion towards interchain migration through cation-dipole interaction, thus, enabling uniform Li-ion diffusion. Electrochemical measurements of Li | |PHS-coated-Cu coin cells demonstrate an average Coulombic efficiency of 99.46% at 1 mA/cm2, 6 mAh/cm2 and 25 °C. Moreover, when the PHS-coated Li metal negative electrode is paired with a high-areal-capacity LiNi0.83Co0.11Mn0.06O2-based positive electrode in multi-layer pouch cell configuration, the battery delivers an initial capacity of 6.86 Ah (corresponding to a specific energy of 489.7 Wh/kg) and, a 91.1% discharge capacity retention after 150 cycles at 2.5 mA/cm2, 25 °C and 172 kPa.
The use of double-mode RR Lyrae stars as robust distance and metallicity indicators
Authors: Chen Xiaodian , Zhang Jianxing , Wang Shu , Deng Licai
Published: June 2023

RR Lyrae stars are one of the primary distance indicators for old stellar populations such as globular clusters, dwarf galaxies and galaxies. Typically, fundamental-mode RR Lyr stars are used for distance measurements, and their accuracy is strongly limited by the dependence of absolute magnitudes on metallicity, in both the optical and infrared bands. Here, we report the discovery of a period–(period ratio)–metallicity relation for double-mode RR Lyr stars, which can predict metallicity as accurately as the low-resolution spectra. With theoretical and observational evidence, we propose that the period–luminosity relation of double-mode RR Lyr stars is not affected by the metallicity. Combining the Large Magellanic Cloud distance and Gaia parallaxes, we calibrate the zero point of the period–luminosity relation to an error of 0.022 mag, which means that in the best case double-mode RR Lyr stars can anchor galaxy distances to an accuracy of 1.0%. For four globular clusters and two dwarf galaxies, we obtain distances using double-mode RR Lyr stars with a distance accuracy of 2–3% and 1–2%, respectively. With future telescopes such as the China Space Station Telescope and the Vera C. Rubin Observatory, double-mode RR Lyr stars will be established as an independent distance ladder in the near-field universe.
No thick carbon dioxide atmosphere on the rocky exoplanet TRAPPIST-1 c
Authors: Zieba Sebastian , Kreidberg Laura , Ducrot Elsa , Gillon Michaël , Morley Caroline , Schaefer Laura , Tamburo Patrick , Koll Daniel D. B. , Lyu Xintong , Acuña Lorena , Agol Eric , Iyer Aishwarya R. , Hu Renyu , Lincowski Andrew P. , Meadows Victoria S. , Selsis Franck , Bolmont Emeline , Mandell Avi M. , Suissa Gabrielle
Published: June 2023

Seven rocky planets orbit the nearby dwarf star TRAPPIST-1, providing a unique opportunity to search for atmospheres on small planets outside the Solar System1. Thanks to the recent launch of the James Webb Space Telescope (JWST), possible atmospheric constituents such as carbon dioxide (CO2) are now detectable2,3. Recent JWST observations of the innermost planet TRAPPIST-1 b showed that it is most probably a bare rock without any CO2 in its atmosphere4. Here we report the detection of thermal emission from the dayside of TRAPPIST-1 c with the Mid-Infrared Instrument (MIRI) on JWST at 15 µm. We measure a planet-to-star flux ratio of fp/f⁎ = 421 ± 94 parts per million (ppm), which corresponds to an inferred dayside brightness temperature of 380 ± 31 K. This high dayside temperature disfavours a thick, CO2-rich atmosphere on the planet. The data rule out cloud-free O2/CO2 mixtures with surface pressures ranging from 10 bar (with 10 ppm CO2) to 0.1 bar (pure CO2). A Venus-analogue atmosphere with sulfuric acid clouds is also disfavoured at 2.6σ confidence. Thinner atmospheres or bare-rock surfaces are consistent with our measured planet-to-star flux ratio. The absence of a thick, CO2-rich atmosphere on TRAPPIST-1 c suggests a relatively volatile-poor formation history, with less than $${9.5}_{-2.3}^{+7.5}$$

9.5

−
2.3

+
7.5

Earth oceans of water. If all planets in the system formed in the same way, this would indicate a limited reservoir of volatiles for the potentially habitable planets in the system.
Control and coding of pupil size by hypothalamic orexin neurons
Authors: Grujic Nikola , Tesmer Alexander , Bracey Ed , Peleg-Raibstein Daria , Burdakov Denis
Published: June 2023

Brain orexin (hypocretin) neurons are implicated in sleep–wake switching and reward-seeking but their roles in rapid arousal dynamics and reward perception are unclear. Here, cell-specific stimulation, deletion and in vivo recordings revealed strong correlative and causal links between pupil dilation—a quantitative arousal marker—and orexin cell activity. Coding of arousal and reward was distributed across orexin cells, indicating that they specialize in rapid, multiplexed communication of momentary arousal and reward states.
Reappraising the evolutionary history of the largest known gecko, the presumably extinct Hoplodactylus delcourti, via high-throughput sequencing of archival DNA
Authors: Heinicke Matthew P. , Nielsen Stuart V. , Bauer Aaron M. , Kelly Ryan , Geneva Anthony J. , Daza Juan D. , Keating Shannon E. , Gamble Tony
Published: June 2023

Hoplodactylus delcourtiis a presumably extinct species of diplodactylid gecko known only from a single specimen of unknown provenance. It is by far the largest known gekkotan, approximately 50% longer than the next largest-known species. It has been considered a member of the New Zealand endemic genusHoplodactylusbased on external morphological features including shared toe pad structure. We obtained DNA from a bone sample of the only known specimen to generate high-throughput sequence data suitable for phylogenetic analysis of its evolutionary history. Complementary sequence data were obtained from a broad sample of diplodactylid geckos. Our results indicate that the species is not most closely related to extantHoplodactylusor any other New Zealand gecko. Instead, it is a member of a clade whose living species are endemic to New Caledonia. Phylogenetic comparative analyses indicate that the New Caledonian diplodactylid clade has evolved significantly more disparate body sizes than either the Australian or New Zealand clades. Toe pad structure has changed repeatedly across diplodactylids, including multiple times in the New Caledonia clade, partially explaining the convergence in form betweenH. delcourtiand New ZealandHoplodactylus. Based on the phylogenetic results, we placeH. delcourtiin a new genus.
Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats
Authors: Johra Fatima Tuj , Hossain Sukria , Jain Preeti , Bristy Anika Tabassum , Emran Tushar , Ahmed Rezwana , Sharker Shazid Md , Bepari Asim Kumar , Reza Hasan Mahmud
Published: June 2023

Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects ofGanoderma lucidumagainst CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract ofG. lucidumat 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1β, IL-6, IL-10, TNF-α, and TGF-β genes. Gas Chromatography-Mass Spectroscopy (GC–MS) analysis revealed thatG. lucidumis rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with theG. lucidumextract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by theG. lucidumtreatment. The increased expression of inflammatory cytokines TNF-α, TGF-β, IL-1 β, and IL-6 were markedly suppressed byG. lucidumextract treatment.G. lucidumalso prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests thatG. lucidumextract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.
Meridional binocular rivalry reveals a trace of uncorrected oblique input during development in the adult brain
Authors: Serero Gad , Lev Maria , Polat Uri
Published: June 2023

Binocular rivalry (BR) is a visual perception phenomenon that occurs when each eye perceives different images and stimuli, causing alternating monocular dominance. To measure BR, many studies have used two monocular conflicting images to induce monocular alternations. Here we chose a group of participants with oblique astigmatism (OA) and who produced blur on the orthogonal oblique meridian in each eye, resulting in two conflicting images, which may enhance the stimulation of monocular alternations. Our results show that OA participants tend to have a high rate of BR when viewing natural images, whereas the control group does not have BR for the same images. We suggest that this low ability to fuse could indicate the presence of a trace due to uncorrected vision during the critical period, which could be retained in the adult brain.
Infants’ interoception is associated with eye contact in dyadic social interactions
Authors: Imafuku Masahiro , Yoshimoto Hiromasa , Hiraki Kazuo
Published: June 2023

Interoception, that is, the perception of visceral stimuli, is the basis of socio-emotional development. However, no studies have demonstrated the relationship between the two in infants. This study aimed to elucidate the relationship between interoception and social behavior in infants and mothers. Visual preference for cardio-visual synchronous and asynchronous stimuli was assessed using a preferential-looking paradigm in 6-month infants and their mothers. The infant–mother interaction was also measured to assess social behavior, such as eye contact and positive facial expressions. The results showed that infants looked at asynchronous cardio-visual stimuli longer than synchronous cardio-visual stimuli, whereas mothers looked at synchronous cardio-visual stimuli longer than asynchronous cardio-visual stimuli. The proportion of looking time toward asynchronous cardio-visual stimuli in infants was positively correlated with infant–mother gaze and affect (positive facial expression) synchrony. Furthermore, mediation analyses showed that the relationship between infants’ interoception and eye contact behavior is attributable to mother’s positive facial expression. Our findings suggest that in infant–mother interactions, infants’ interoception may play a role in eye contact behavior through the mother's positive facial expression, highlighting the importance of infants’ interoception on social cognitive development.
Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
Authors: Lee Kyoungmin , Lee Jongwon , Choi Jungmin , Sim Sung Hoon , Kim Jeong Eun , Kim Min Hwan , Park Yeon Hee , Kim Jee Hyun , Koh Su-Jin , Park Kyong Hwa , Kang Myoung Joo , Ahn Mi Sun , Lee Kyoung Eun , Kim Hee-Jun , Ahn Hee Kyung , Kim Han Jo , Park Keon Uk , Park In Hae
Published: June 2023

We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.
Explainable sequence-to-sequence GRU neural network for pollution forecasting
Authors: Mirzavand Borujeni Sara , Arras Leila , Srinivasan Vignesh , Samek Wojciech
Published: June 2023

The goal of pollution forecasting models is to allow the prediction and control of the air quality. Non-linear data-driven approaches based on deep neural networks have been increasingly used in such contexts showing significant improvements w.r.t. more conventional approaches like regression models and mechanistic approaches. While such deep learning models were deemed for a long time as black boxes, recent advances in eXplainable AI (XAI) allow to look through the model’s decision-making process, providing insights into decisive input features responsible for the model’s prediction. One XAI technique to explain the predictions of neural networks which was proven useful in various domains is Layer-wise Relevance Propagation (LRP). In this work, we extend the LRP technique to a sequence-to-sequence neural network model with GRU layers. The explanation heatmaps provided by LRP allow us to identify important meteorological and temporal features responsible for the accumulation of four major pollutants in the air ($$\text {PM}_{10}$$

PM
10

, $$\text {NO}_{2}$$

NO
2

, $$\text {NO}$$
NO
, $$\text {O}_{3}$$

O
3

), and our findings can be backed up with prior knowledge in environmental and pollution research. This illustrates the appropriateness of XAI for understanding pollution forecastings and opens up new avenues for controlling and mitigating the pollutants’ load in the air.
Impact of heat stress, water stress, and their combined effects on the metabolism and transcriptome of grape berries
Authors: Hewitt Seanna , Hernández-Montes Esther , Dhingra Amit , Keller Markus
Published: June 2023

Recurring heat and drought episodes present challenges to the sustainability of grape production worldwide. We investigated the impacts of heat and drought stress on transcriptomic and metabolic responses of berries from two wine grape varieties. Cabernet Sauvignon and Riesling grapevines were subjected to one of four treatments during early fruit ripening: (1) drought stress only, (2) heat stress only, (3) simultaneous drought and heat stress, (4) no drought or heat stress (control). Berry metabolites, especially organic acids, were analyzed, and time-course transcriptome analysis was performed on samples before, during, and after the stress episode. Both alone and in conjunction with water stress, heat stress had a much more significant impact on berry organic acid content, pH, and titratable acidity than water stress. This observation contrasts with previous reports for leaves, which responded more strongly to water stress, indicating that grape berries display a distinct, organ-specific response to environmental stresses. Consistent with the metabolic changes, the global transcriptomic analysis revealed that heat stress had a more significant impact on gene expression in grape berries than water stress in both varieties. The differentially expressed genes were those associated with the tricarboxylic acid cycle and glyoxylate cycle, mitochondrial electron transport and alternative respiration, glycolysis and gluconeogenesis, carbohydrate allocation, ascorbate metabolism, and abiotic stress signaling pathways. Knowledge regarding how environmental stresses, alone and in combination, impact the berry metabolism of different grape varieties will form the basis for developing recommendations for climate change mitigation strategies and genetic improvement.
Placebo effects on nausea and motion sickness are resistant to experimentally-induced stress
Authors: Jacob Carmen , Olliges Elisabeth , Haile Anja , Hoffmann Verena , Jacobi Benjamin , Steinkopf Leander , Lanz Marina , Wittmann Marc , Tschöp Matthias H. , Meissner Karin
Published: June 2023

Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains unclear whether stress has an impact on these effects. The aim of this experimental study was to investigate the interplay between acute stress and placebo effects in nausea. 80 healthy female volunteers susceptible to motion sickness were randomly assigned to either the Maastricht Acute Stress Test or a non-stress control condition, and to either placebo treatment or no treatment. Nausea was induced by a virtual vection drum and behavioral, psychophysiological as well as humoral parameters were repeatedly assessed. Manipulation checks confirmed increased cortisol levels and negative emotions in the stressed groups. In the non-stressed groups, the placebo intervention improved nausea, symptoms of motion sickness, and gastric myoelectrical activity (normo-to-tachy (NTT) ratio). In the stressed groups, the beneficial effects of the placebo intervention on nausea and motion sickness remained unchanged, whereas no improvement of the gastric NTT ratio was observed. Results suggest that placebo effects on symptoms of nausea and motion sickness are resistant to experimentally-induced stress. Stress most likely interfered with the validity of the gastric NTT ratio to measure nausea and thus the gastric placebo effect.
Optical and rogue type soliton solutions of the (2+1) dimensional nonlinear Heisenberg ferromagnetic spin chains equation
Authors: Islam Shariful , Halder Bishnupada , Refaie Ali Ahmed
Published: June 2023

In this study, the uses of unified method for finding solutions of a nonlinear Schrödinger equation that describes the nonlinear spin dynamics of (2+1) dimensional Heisenberg ferromagnetic spin chains equation. We successfully construct solutions to these equations. For each of the derived solutions, we provide the parametric requirements for the existence of a valid soliton. In order to visualize some of the discovered solutions, we plot the 2D and 3D graphics. The results of this investigation, which have been presented, might be useful in elucidating the model's physical significance. These are a highly useful tool for studying how electrical solitons, which travel as voltage waves in nonlinear dispersive media, spread out, as well as for doing various physical calculations. The study’s findings, which have been disclosed, might be useful in illuminating the models under consideration's physical significance and electrical field.
Comprehensive power quality performance assessment for electrical system of a nuclear research reactor
Authors: Elsotohy Asmaa M. , Soliman Ahmed Mohammed Attiya , Adail Ahmed S. , Eisa Ayman A. , Othman El-said A
Published: June 2023

Studying the power quality (PQ) is an essential issue to ensure the safe and accurate operation of sensitive equipment particularly for nuclear installations. Assessment of PQ involves collecting and analysing data resources and then evaluating it with reference to PQ standards. There are many alternatives for PQ and it is difficult to make an appropriate selection among them in the existence of their multiple criteria which are usually conflicted. So this selection subject can be classified as a Multi Criteria Decision Making (MCDM) problem. To do so, a reliable and scientific method for studying and evaluating the overall system PQ is required. This study aims to assess performance of PQ for the electrical power system at a Nuclear Research Reactor (NRR) during a certain period using multiple measures for the most decisive PQ phenomena. It focuses on a number of the most important PQ phenomena namely frequency fluctuation (deviation), unbalances of current and voltage, current and voltage harmonic distortion, flicker and power factor. After combining all results into six samples (alternatives), the criteria weights are determined based on an objective method for weighting which is called CRITIC method. Then, the alternatives are ranked using compromise MCDM method-VIKOR method. The obtained results are analyzed and discussed to evaluate performance of NRR electrical system from the PQ view. It showed that the compromise solution that obtained by CRITIC-VIKOR can be a guide to facilitate the PQ evaluation of nuclear installation electrical system. Also, it can empower the operators with the benefits of benchmarking and monitoring a single index instead of several indices. Moreover, it is very useful for helping stakeholders to understand how the PQ performance changes under a certain operating condition of the facility. Finally, it is can be considered as a good model to weight each PQ phenomena and identify the time intervals for best and worst total PQ in NRR.
Circularly polarized differential intra-oral antenna design validation and characterization for tongue drive system
Authors: Ahlawat Sarita , Kanaujia Binod Kumar , Rambabu Karumudi , Peter Ildiko , Matekovits Ladislau
Published: June 2023

Assistive devices are becoming increasingly popular for physically disabled persons suffering tetraplegia and spinal cord injuries. Intraoral tongue drive system (iTDS) is one of the most feasible and non-invasive assistive technology (AT), which utilises the transferring and inferring of user intentions through different tongue gestures. Wireless transferring is of prime importance and requires a suitable design of the intra-oral antenna. In this paper, a compact circularly polarized differential intra-oral antenna is designed, and its performance is analysed within heterogeneous multilayer mouth and head models. It works at 2.4 GHz in the Industrial, Scientific, and Medical (ISM) band. The footprint of the differential antenna prototype is 0.271 λg$$\times$$
×
0.271 λg$$\times$$
×
0.015 λg. It is achieved using two pairs of spiral segments loaded in diagonal form near the edges of the central rotated square slot and a high dielectric constant substrate. Its spiral-slotted geometry further provides the desired swirling and miniaturization at the desired frequency band for both mouth scenarios. Additionally, corner triangular slits on the radiating patch assist in tuning the axial ratio (< 3 dB) in the desired ISM band. To validate the performance of the proposed in-mouth antenna, the measurement was carried out using the minced pork and the saline solution for closed and opened mouth cases, respectively. The measured − 10 dB impedance bandwidth and peak gain values in the minced pork are from 2.28 to 2.53 GHz (10.39%) and − 18.17 dBi, respectively, and in the saline solution, are from 2.3 to 2.54 GHz (9.92%) and − 15.47 dBi, respectively. Further, the specific absorption rate (SAR) is estimated, and the data communication link is computed with and without a balun loss. This confirms that the proposed differential intraoral antenna can establish direct interfacing at the RF front end of the intraoral tongue drive system.
Mid- to late Holocene sea-level rise recorded in Hells Bells 234U/238U ratio and geochemical composition
Authors: Schorndorf Nils , Frank Norbert , Ritter Simon M. , Warken Sophie F. , Scholz Christian , Keppler Frank , Scholz Denis , Weber Michael , Aviles Olguin Jeronimo , Stinnesbeck Wolfgang
Published: June 2023

Hells Bells are underwater secondary carbonates discovered in sinkholes (cenotes) southeast of Cancun on the north-eastern Yucatán peninsula, Mexico. These authigenic calcite precipitates, reaching a length of up to 4 m, most likely grow in the pelagic redoxcline. Here we report on detailed 230Th/U-dating and in-depth geochemical and stable isotope analyses of specimens from cenotes El Zapote, Maravilla and Tortugas. Hells Bells developed since at least ~ 8000 years ago, with active growth until present day. Initial (234U/238U) activity ratios (δ234U0) in Hells Bells calcite decreas from 55 to 15‰ as sea level converges toward its present state. The temporal evolution of the geochemistry and isotope composition of Hells Bells calcites thus appears to be closely linked to sea-level rise and reflects changing hydrological conditions (desalinization) of the aquifer. We suggest that decelerated leaching of excess 234U from the previously unsaturated bedrock traces Holocene relative sea-level rise. Considering this proxy, the resulting mean sea-level reconstruction contains half as much scatter, i.e. improves by a factor of two, when compared to previously published work for the period between 8 and 4 ky BP.
The plasma degradome reflects later development of NASH fibrosis after liver transplant
Authors: Li Jiang , Sato Toshifumi , Hernández-Tejero María , Beier Juliane I. , Sayed Khaled , Benos Panayiotis V. , Wilkey Daniel W. , Humar Abhinav , Merchant Michael L. , Duarte-Rojo Andres , Arteel Gavin E.
Published: June 2023

Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease and decreased survival. Lack of risk stratification strategies hampers early intervention against development of post-LT NASH fibrosis. The liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., ‘degradome’) of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether liver injury caused by post-LT NASH would yield a unique degradome profile that is predictive of severe post-LT NASH fibrosis, a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without) was performed. Total plasma peptides were isolated and analyzed by 1D-LC–MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC–MS/MS yielded ~ 2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (~ 15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. The plasma degradome profile of post-LT patients yielded stark difference based on later development of post-LT NASH fibrosis. This approach could yield new “fingerprints” that can serve as minimally-invasive biomarkers of negative outcomes post-LT.
Host–pathogen interaction unveiled by immune, oxidative stress, and cytokine expression analysis to experimental Saprolegnia parasitica infection in Nile tilapia
Authors: El Gamal Samar A. , Adawy Rawia Saad , Zaki Viola Hassan , Zahran Eman
Published: June 2023

The present study evaluated the pathogenicity, immunological, and oxidant/antioxidant responses against Saprolegnia parasitica (S. parasitica) infection in Nile tilapia (Oreochromis niloticus). Three groups of Nile tilapia were assigned as the control group (no zoospores exposure). The other two groups were challenged by Saprolegnia zoospores; one was used for sampling, and the other for mortality monitoring. The study lasted 3 weeks and was sampled at three point times at 1, 2, and 3 weeks. Results showed that S. parasitica zoospores were pathogenic to Nile tilapia, causing a cumulative mortality rate of 86.6%. Immunoglobulin M and C- reactive protein (IgM and CRP) levels showed a similar trend being significantly (P < 0.05, P < 0.001) higher in the infected group at weeks 1, 2, and 3, respectively, compared to the control group. Oxidant and antioxidant parameters in gills revealed that Malondialdehyde (MDA) level was significantly higher in the infected group compared to the control group. While catalase, glutathione peroxidase, and superoxide dismutase (CAT, GSH, and SOD) levels were significantly decreased in the infected group compared to the control group. Compared to the control, the tumor necrosis factor-α (TNF-α) gene was firmly upregulated in gill tissue at all-time points, particularly at day 14 post-infection. Meanwhile, Interleukin 1-β (IL-1 β) gene was significantly upregulated only at days 7 and 14 post-infection compared to control. Histopathological examination revealed destructive and degenerative changes in both skin and gills of experimentally infected Nile tilapia. Our findings suggest that Nile tilapia-S. parasitica infection model was successful in better understanding of pathogenicity and host (fish)-pathogen (oomycete) interactions, where the induced oxidative stress and upregulation of particular immune biomarkers in response to S. parasitica infection may play a crucial role in fish defense against oomycetes in fish.