bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel
Authors: Zhang Mingfeng , Shan Yuanyue , Pei Duanqing 
Published: March 2023

AbstractThe transmembrane voltage gradient is a general physico-chemical cue that regulates diverse biological function through voltage-gated ion channels. How voltage sensing mediates ion flows remains unknown at the molecular level. Here, we report six conformations of the human Eag2 (hEag2) ranging from closed, pre-open, open, and pore dilation but non-conducting states captured by cryo-electron microscopy (cryo-EM). These multiple states illuminate dynamics of the selectivity filter and ion permeation pathway with delayed rectifier properties and Cole-Moore effect at the atomic level. Mechanistically, a short S4-S5 linker is coupled with the constrict sites to mediate voltage transducing in a non-domain-swapped configuration, resulting transitions for constrict sites of F464 and Q472 from gating to open state stabilizing for voltage energy transduction. Meanwhile, an additional potassium ion occupied at positions S6 confers the delayed rectifier property and Cole-Moore effects. These results provide insight into voltage transducing and potassium current across membrane, and shed light on the long-sought Cole-Moore effects.
MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients
Authors: Zhong Zhenggang , Li Jiabao , Zhong Jiayuan , Huang Yilin , Hu Jiaqi , Zhang Piao , Zhang Baowen , Jin Yabin , Luo Wei , Liu Rui , Zhang Yuhu , Ling Fei 
Published: March 2023

AbstractOne of the important pathological features of Parkinson’s disease (PD) is the pathological aggregation of α-synuclein (α-Syn) in the substantia nigra. Preventing the aggregation of α-Syn has become a potential strategy for treating PD. However, the molecular mechanism of α-Syn aggregation is unclear. In this study, using the dynamic network biomarker (DNB) method, we first identified the critical time point when α-Syn undergoes pathological aggregation based on a SH-SY5Y cell model and found that DNB genes encode transcription factors that regulated target genes that were differentially expressed. Interestingly, we found that these DNB genes and their neighbouring genes were significantly enriched in the cellular senescence pathway and thus proposed that the DNB genes HSF1 and MAPKAPK2 regulate the expression of the neighbouring gene SERPINE1. Notably, in Gene Expression Omnibus (GEO) data obtained from substantia nigra, prefrontal cortex and peripheral blood samples, the expression level of MAPKAPK2 was significantly higher in PD patients than in healthy people, suggesting that MAPKAPK2 has potential as an early diagnostic biomarker of diseases related to pathological aggregation of α-Syn, such as PD. These findings provide new insights into the mechanisms underlying the pathological aggregation of α-Syn.
Metabolomics integrated with machine learning to discriminate the geographic origin of Rougui Wuyi rock tea
Authors: Peng Yifei , Zheng Chao , Guo Shuang , Gao Fuquan , Wang Xiaxia , Du Zhenghua , Gao Feng , Su Feng , Zhang Wenjing , Yu Xueling , Liu Guoying , Liu Baoshun , Wu Chengjian , Sun Yun , Yang Zhenbiao , Hao Zhilong , Yu Xiaomin 
Published: March 2023

AbstractThe geographic origin of agri-food products contributes greatly to their quality and market value. Here, we developed a robust method combining metabolomics and machine learning (ML) to authenticate the geographic origin of Wuyi rock tea, a premium oolong tea. The volatiles of 333 tea samples (174 from the core region and 159 from the non-core region) were profiled using gas chromatography time-of-flight mass spectrometry and a series of ML algorithms were tested. Wuyi rock tea from the two regions featured distinct aroma profiles. Multilayer Perceptron achieved the best performance with an average accuracy of 92.7% on the training data using 176 volatile features. The model was benchmarked with two independent test sets, showing over 90% accuracy. Gradient Boosting algorithm yielded the best accuracy (89.6%) when using only 30 volatile features. The proposed methodology holds great promise for its broader applications in identifying the geographic origins of other valuable agri-food products.
Synthetic multiantigen MVA vaccine COH04S1 and variant-specific derivatives protect Syrian hamsters from SARS-CoV-2 Omicron subvariants
Authors: Wussow Felix , Kha Mindy , Kim Taehyun , Ly Minh , Yll-Pico Marcal , Kar Swagata , Lewis Mark G. , Chiuppesi Flavia , Diamond Don J. 
Published: March 2023

AbstractEmerging SARS-CoV-2 Omicron subvariants continue to disrupt COVID-19 vaccine efficacy through multiple immune mechanisms including neutralizing antibody evasion. We developed COH04S1, a synthetic modified vaccinia Ankara vector that co-expresses Wuhan-Hu-1-based spike and nucleocapsid antigens. COH04S1 demonstrated efficacy against ancestral virus and Beta and Delta variants in animal models and was safe and immunogenic in a Phase 1 clinical trial. Here, we report efficacy of COH04S1 and analogous Omicron BA.1- and Beta-specific vaccines to protect Syrian hamsters from Omicron subvariants. Despite eliciting strain-specific antibody responses, all three vaccines protect hamsters from weight loss, lower respiratory tract infection, and lung pathology following challenge with Omicron BA.1 or BA.2.12.1. While the BA.1-specifc vaccine affords consistently improved efficacy compared to COH04S1 to protect against homologous challenge with BA.1, all three vaccines confer similar protection against heterologous challenge with BA.2.12.1. These results demonstrate efficacy of COH04S1 and variant-specific derivatives to confer cross-protective immunity against SARS-CoV-2 Omicron subvariants.
Negativity drives online news consumption
Authors: Robertson Claire E. , Pröllochs Nicolas , Schwarzenegger Kaoru , Pärnamets Philip , Van Bavel Jay J. , Feuerriegel Stefan 
Published: March 2023

AbstractOnline media is important for society in informing and shaping opinions, hence raising the question of what drives online news consumption. Here we analyse the causal effect of negative and emotional words on news consumption using a large online dataset of viral news stories. Specifically, we conducted our analyses using a series of randomized controlled trials (N = 22,743). Our dataset comprises ~105,000 different variations of news stories from Upworthy.com that generated ∼5.7 million clicks across more than 370 million overall impressions. Although positive words were slightly more prevalent than negative words, we found that negative words in news headlines increased consumption rates (and positive words decreased consumption rates). For a headline of average length, each additional negative word increased the click-through rate by 2.3%. Our results contribute to a better understanding of why users engage with online media.
Adapted clustering method for generic analysis of histological fibrosis staining as an open source tool
Authors: Remes Anca , Noormalal Marie , Schmiedel Nesrin , Frey Norbert , Frank Derk , Müller Oliver J. , Graf Markus 
Published: March 2023

AbstractPathological remodeling of the extracellular matrix is a hallmark of cardiovascular disease. Abnormal fibrosis causes cardiac dysfunction by reducing ejection fraction and impairing electrical conductance, leading to arrhythmias. Hence, accurate quantification of fibrosis deposition in histological sections is of extreme importance for preclinical and clinical studies. Current automatic tools do not perform well under variant conditions. Moreover, users do not have the option to evaluate data from staining methods of their choice according to their purpose. To overcome these challenges, we underline a novel machine learning-based tool (FibroSoft) and we show its feasibility in a model of cardiac hypertrophy and heart failure in mice. Our results demonstrate that FibroSoft can identify fibrosis in diseased myocardium and the obtained results are user-independent. In addition, the results acquired using our software strongly correlate to those obtained by Western blot analysis of collagen 1 expression. Additionally, we could show that this method can be used for Masson’s Trichrome and Picosirius Red stained histological images. The evaluation of our method also indicates that it can be used for any particular histology segmentation and quantification. In conclusion, our approach provides a powerful example of the feasibility of machine learning strategies to enable automatic analysis of histological images.
A microwave scattering spectral method to detect the nanomechanical vibrations embedded in a superconducting qubit
Authors: Gao H. Y. , Wei L. F. 
Published: March 2023

AbstractNanomechanical resonators (NMRs), as the quantum mechanical sensing probers, have played the important roles for various high-precision quantum measurements. Differing from the previous emission spectral probes (i.e., the NMR modified the atomic emission), in this paper we propose an alternative approach, i.e., by probing the scattering spectra of the quantum mechanical prober coupled to the driving microwaves, to characterize the physical features of the NMR embedded in a rf-SQUID based superconducting qubit. It is shown that, from the observed specifical frequency points in the spectra, i.e., either the dips or the peaks, the vibrational features (i.e., they are classical vibration or quantum mechanical one) and the physical parameters (typically such as the vibrational frequency and displacements) of the NMR can be determined effectively. The proposal is feasible with the current technique and should be useful to design the desired NMRs for various quantum metrological applications.
Synthesis and structure–activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors
Authors: Moghadam Farid Sara , Noori Milad , Nazari Montazer Mohammad , Khalili Ghomi Minoo , Mollazadeh Marjan , Dastyafteh Navid , Irajie Cambyz , Zomorodian Kamiar , Mirfazli Seyedeh Sara , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Larijani Bagher , Iraji Aida , Mahdavi Mohammad 
Published: March 2023

AbstractIn this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.
Bio-efficacy of aluminum phosphide and cypermethrin against some physiological and biochemical aspects of Chrysomya megacephala maggots
Authors: Tony Mahran , Ashry Mahmoud , Tanani Mohammad M. A. , Abdelreheem Abdelbaset M. A. , Abdel-Samad Mohammad R. K. 
Published: March 2023

AbstractCarrion flies play a significant role in forensic entomotoxicology, where they are employed as alternative samples when traditional samples are unavailable. In situations of poisoned death, these toxins disrupt insect development and affect forensic entomology analyses. So, forensic entomotoxicologists must be aware of this impact. The present study aimed to determine the effects of aluminum phosphide (AlP) and cypermethrin (CP) on the biochemical parameters and antioxidant enzymes of the third instar of Chrysomya megacephala maggots. C. megacephala was reared on normal and poisoned rabbit carcasses with aluminum phosphide and cypermethrin. The third larval instar of C. megacephala was studied using by spectrophotometer for detection of total protein, (TP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione s-transferase (GST), catalase (CAT) and malondialdehyde (MDA). The results indicated to significantly decrease of TP, TAC, SOD, GST and CAT and increase of AST, ALT and MDA in the maggots reared on the poisoned carcasses with AlP or CP compared with control group. In conclusion, the tested insecticides brought about a decrease antioxidant enzyme activity and increase of MDA could be involved in free radicals in C. megacephala larvae leading to oxidative stress by these insecticidal components.
Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1
Authors: Bhandari Seema Khattri , Wiest Nathaniel , Sallmyr Annahita , Du Ruofei , Ferry Laure , Defossez Pierre-Antoine , Tomkinson Alan E. 
Published: March 2023

AbstractDNA ligase I (LigI), the predominant enzyme that joins Okazaki fragments, interacts with PCNA and Pol δ. LigI also interacts with UHRF1, linking Okazaki fragment joining with DNA maintenance methylation. Okazaki fragments can also be joined by a relatively poorly characterized DNA ligase IIIα (LigIIIα)-dependent backup pathway. Here we examined the effect of LigI-deficiency on proteins at the replication fork. Notably, LigI-deficiency did not alter the kinetics of association of the PCNA clamp, the leading strand polymerase Pol ε, DNA maintenance methylation proteins and core histones with newly synthesized DNA. While the absence of major changes in replication and methylation proteins is consistent with the similar proliferation rate and DNA methylation levels of the LIG1 null cells compared with the parental cells, the increased levels of LigIIIα/XRCC1 and Pol δ at the replication fork and in bulk chromatin indicate that there are subtle replication defects in the absence of LigI. Interestingly, the non-replicative histone H1 variant, H1.0, is enriched in the chromatin of LigI-deficient mouse CH12F3 and human 46BR.1G1 cells. This alteration was not corrected by expression of wild type LigI, suggesting that it is a relatively stable epigenetic change that may contribute to the immunodeficiencies linked with inherited LigI-deficiency syndrome.
Characterization of pancreatic cancer with ultra-low tumor mutational burden
Authors: Imamura Taisuke , Ashida Ryo , Ohshima Keiichi , Uesaka Katsuhiko , Sugiura Teiichi , Ohgi Katsuhisa , Yamada Mihoko , Otsuka Shimpei , Hatakeyama Keiichi , Nagashima Takeshi , Sugino Takashi , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken 
Published: March 2023

AbstractIn pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (< 5.0, ≥ 1.0), or Ultra-low (< 1.0). Nineteen samples (20%) were classified as TMB-low, and 74 (80%) were classified as TMB-ultra-low; no samples were TMB-high. TMB-ultra-low PC had significantly fewer borderline resectable lesions (P = 0.028) and fewer adenosquamous carcinomas (P = 0.003) than TBM-low PC. Furthermore, the TMB-ultra-low PC showed significantly lower detection rates of driver mutations and copy number variations. Microsatellite instability was not significantly correlated with the TMB status. The TMB-ultra-low PC had a significantly better prognosis than TBM-low PC (P = 0.023). A multivariate analysis identified TMB-ultra-low PC as an independent favorable prognostic factor (hazard ratio, 2.11; P = 0.019). A gene expression analysis showed that TMB-ultra-low PC was associated with reduced TP53 inactivation (P = 0.003) and reduced chromosomal instability (P = 0.001) compared to TBM-low PC. TMB-ultra-low PC had specific gene expression signatures and a better prognosis than TMB-low PC.
Ultrafast hole relaxation dynamics in quantum dots revealed by two-dimensional electronic spectroscopy
Authors: Brosseau Patrick J. , Geuchies Jaco J. , Jasrasaria Dipti , Houtepen Arjan J. , Rabani Eran , Kambhampati Patanjali 
Published: March 2023

AbstractElucidating the population dynamics of correlated electron-hole pairs (bound excitons) in semiconducting quantum dots (QDs) is key for developing our fundamental understanding of nanoscale photophysics as well as for the optimal design of devices, such as lasers. For decades, it was assumed that holes did not contribute to band edge bleach signals in QDs. Here, we employ two-dimensional electronic spectroscopy to monitor electron and hole dynamics in both CdSe and CdSe/CdS/ZnS QDs to probe electron and hole dynamics. Based on a combination of time and frequency resolution, we observe a previously unresolved bleaching signal in CdSe QDs on timescales faster than 30 fs due to hole cooling. Atomistic semiempirical pseudopotential calculations are used to rationalize the order of magnitude difference in the observed hole dynamics in CdSe and CdSe/CdS/ZnS QDs. This picture advances our understanding of QD excitonics past the prevailing continuum effective mass theories generally used to describe QD electronic structure and dynamics.
A Community-Based Approach to Longitudinal Language Research With Racially and Ethnically Minoritized Autistic Young Adults: Lessons Learned and New Directions
Authors: Girolamo Teresa , Ghali Samantha , Eigsti Inge-Marie 
Published: March 2023

Purpose:
Language and autism research each typically excludes racially and ethnically minoritized (REM) autistic individuals. In addition, in the case of autistic individuals with language impairment, investigators often approach caregivers to discuss research participation, rather than autistic individuals themselves. This gap limits the ecological validity of language research in autism. To address this gap, this clinical focus article describes strategies for engaging REM autistic young adults with language impairment using lessons learned from 5 years of longitudinal research with this population. This approach involved an ongoing community partnership, as well as participatory partnerships with REM autistic individuals and community stakeholders, consistent with a “slow science” approach.

Conclusions:
The approach yielded excellent retention of participants over 5 years and led to co-development of research projects aimed at priorities described by REM autistic individuals and their families, including understanding self-determination, social determinants of health, and language variability in autistic REM individuals with language impairment. Findings support the utility of community-based methods with autistic REM young adults with language impairment, with key takeaways for diversifying research while replicating, extending, and building theory.
New optimal planning strategy for plug‐in electric vehicles charging stations in a coupled power and transportation network
Authors: Keleshteri Sobhan Farjam , Niknam Taher , Ghiasi Mohammad , Chabok Hossein 
Published: March 2023

AbstractThe use of plug‐in electric vehicles (PEV) and their developing technology can create new challenges to the smart power system. The type, method, and time of charging electric vehicles are also other issues. Allocating and determining the optimal capacity of electric vehicle charging stations (EVCS) is related to the technical requirements of the distribution network. This is economically important for the construction of charging stations. This paper proposes a new approach for optimal siting and sizing of PEV charging stations in a coupled electrical and transportation network. This work presents the problem from a techno‐economic point of view of the electrical network as a multi‐objective problem with the objectives of simultaneously reducing the cost of building EVCSs and active power losses. The Pareto method is used to solve the problem and to display optimal points. In order to carry out the simulation, the proposed method is tested on a case study of the standard IEEE 37‐bus network with a 25‐node transport system and the proposed solution in the subject environment. The Floyd–Warshall method is utilized to determine the shortest travel routes for PEVs. The obtained results confirm the effectiveness of the optimal planning of PEV charging stations.
Eisentherapie bei chronischer Nierenkrankheit: Viel hilft viel oder ist weniger mehr?
Authors: Artunc Ferruh 
Published: March 2023

ZUSAMMENFASSUNGDas Spurenelement Eisen ist ein essenzieller Bestandteil des Hämoglobins. Patienten mit chronischer Nierenkrankheit weisen in hohem Maße einen Eisenmangel auf, was entscheidend zur Entstehung der renalen Anämie beiträgt. Bei diesen Patienten ist daher eine Eisensubstitution zur Behandlung der renalen Anämie erforderlich. Häufig werden hohe Dosen benötigt, die sehr effektiv intravenös verabreicht werden können. Bei der oralen Eisensubstitution erscheint eine täglich alternierende Einnahme Vorteile zu haben. Klinische Studien belegen, dass die Anämie durch eine Eisensubstitution positiv beeinflusst wird und den Bedarf an Erythropoetin reduziert.
Stabilisatoren des HIF-Signalwegs
Authors: Schork Anja 
Published: March 2023

ZUSAMMENFASSUNGMit der Zulassung des ersten Stabilisators des Hypoxie induzierten Faktors (HIF: Hypoxia-Inducible Factor) Roxadustat durch die europäische Zulassungsbehörde EMA (EMA: European Medicines Agency) steht seit August 2021 eine neuartige, orale Therapie der renalen Anämie zur Verfügung. HIF-Stabilisatoren verhindern durch die Inhibition des Enzyms Prolylhydroxylase den Abbau des Transkriptionsfaktors HIF. HIF-Stabilisatoren bewirken eine Wiedererweckung der endogenen Erythropoetinbildung durch die (exkretorisch insuffizienten) Nieren und eine verbesserte Eisenbereitstellung. Aufgrund der bislang kurzen Beobachtungsdauer können jedoch potenzielle Risiken des pleiotropen Wirkmechanismus noch nicht abschließend beurteilt werden. HIF-Stabilisatoren eignen sich zunächst insbesondere für die Behandlung von Patienten mit renaler Anämie und unzureichendem Ansprechen auf die Erythropoetintherapie oder mit einem Wunsch zu einer oralen Therapiealternative.
Euglenozoan kleptoplasty illuminates the early evolution of photoendosymbiosis
Authors: Karnkowska Anna , Yubuki Naoji , Maruyama Moe , Yamaguchi Aika , Kashiyama Yuichiro , Suzaki Toshinobu , Keeling Patrick J. , Hampl Vladimír , Leander Brian S. 
Published: March 2023

Kleptoplasts (kP) are distinct among photosynthetic organelles in eukaryotes (i.e., plastids) because they are routinely sequestered from prey algal cells and function only temporarily in the new host cell. Therefore, the hosts of kleptoplasts benefit from photosynthesis without constitutive photoendosymbiosis. Here, we report that the euglenozoan
Rapaza viridis
has only kleptoplasts derived from a specific strain of green alga,
Tetraselmis
sp., but no canonical plastids like those found in its sister group, the Euglenophyceae.
R. viridis
showed a dynamic change in the accumulation of cytosolic polysaccharides in response to light–dark cycles, and
13
C isotopic labeling of ambient bicarbonate demonstrated that these polysaccharides originate in situ via photosynthesis; these data indicate that the kleptoplasts of
R. viridis
are functionally active. We also identified 276 sequences encoding putative plastid-targeting proteins and 35 sequences of presumed kleptoplast transporters in the transcriptome of
R. viridis
. These genes originated in a wide range of algae other than
Tetraselmis
sp., the source of the kleptoplasts, suggesting a long history of repeated horizontal gene transfer events from different algal prey cells. Many of the kleptoplast proteins, as well as the protein-targeting system, in
R. viridis
were shared with members of the Euglenophyceae, providing evidence that the early evolutionary stages in the green alga-derived secondary plastids of euglenophytes also involved kleptoplasty.