bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian-optimization-assisted discovery of stereoselective aluminum complexes for ring-opening polymerization of racemic lactide
Authors: Wang Xiaoqian , Huang Yang , Xie Xiaoyu , Liu Yan , Huo Ziyu , Lin Maverick , Xin Hongliang , Tong Rong 
Published: June 2023

AbstractStereoselective ring-opening polymerization catalysts are used to produce degradable stereoregular poly(lactic acids) with thermal and mechanical properties that are superior to those of atactic polymers. However, the process of discovering highly stereoselective catalysts is still largely empirical. We aim to develop an integrated computational and experimental framework for efficient, predictive catalyst selection and optimization. As a proof of principle, we have developed a Bayesian optimization workflow on a subset of literature results for stereoselective lactide ring-opening polymerization, and using the algorithm, we identify multiple new Al complexes that catalyze either isoselective or heteroselective polymerization. In addition, feature attribution analysis uncovers mechanistically meaningful ligand descriptors, such as percent buried volume (%Vbur) and the highest occupied molecular orbital energy (EHOMO), that can access quantitative and predictive models for catalyst development.
USP25 regulates KEAP1-NRF2 anti-oxidation axis and its inactivation protects acetaminophen-induced liver injury in male mice
Authors: Cai Changzhou , Ma Huailu , Peng Jin , Shen Xiang , Zhen Xinghua , Yu Chaohui , Zhang Pumin , Ji Feng , Wang Jiewei 
Published: June 2023

AbstractNuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor responsible for mounting an anti-oxidation gene expression program to counter oxidative stress. Under unstressed conditions, Kelch-like ECH-associated protein 1 (KEAP1), an adaptor protein for CUL3 E3 ubiquitin ligase, mediates NRF2 ubiquitination and degradation. We show here that the deubiquitinase USP25 directly binds to KEAP1 and prevents KEAP1’s own ubiquitination and degradation. In the absence of Usp25 or if the DUB is inhibited, KEAP1 is downregulated and NRF2 is stabilized, allowing the cells to respond to oxidative stress more readily. In acetaminophen (APAP) overdose-induced oxidative liver damage in male mice, the inactivation of Usp25, either genetically or pharmacologically, greatly attenuates liver injury and reduces the mortality rates resulted from lethal doses of APAP.
Epistatic interactions between the high pathogenicity island and other iron uptake systems shape Escherichia coli extra-intestinal virulence
Authors: Royer Guilhem , Clermont Olivier , Marin Julie , Condamine Bénédicte , Dion Sara , Blanquart François , Galardini Marco , Denamur Erick 
Published: June 2023

AbstractThe intrinsic virulence of extra-intestinal pathogenic Escherichia coli is associated with numerous chromosomal and/or plasmid-borne genes, encoding diverse functions such as adhesins, toxins, and iron capture systems. However, the respective contribution to virulence of those genes seems to depend on the genetic background and is poorly understood. Here, we analyze genomes of 232 strains of sequence type complex STc58 and show that virulence (quantified in a mouse model of sepsis) emerged in a sub-group of STc58 due to the presence of the siderophore-encoding high-pathogenicity island (HPI). When extending our genome-wide association study to 370 Escherichia strains, we show that full virulence is associated with the presence of the aer or sit operons, in addition to the HPI. The prevalence of these operons, their co-occurrence and their genomic location depend on strain phylogeny. Thus, selection of lineage-dependent specific associations of virulence-associated genes argues for strong epistatic interactions shaping the emergence of virulence in E. coli.
The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii
Authors: Aghabi Dana , Sloan Megan , Gill Grace , Hartmann Elena , Antipova Olga , Dou Zhicheng , Guerra Alfredo J. , Carruthers Vern B. , Harding Clare R. 
Published: June 2023

AbstractIron is essential to cells as a cofactor in enzymes of respiration and replication, however without correct storage, iron leads to the formation of dangerous oxygen radicals. In yeast and plants, iron is transported into a membrane-bound vacuole by the vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii. Here, we assess the role of VIT and iron storage in T. gondii. By deleting VIT, we find a slight growth defect in vitro, and iron hypersensitivity, confirming its essential role in parasite iron detoxification, which can be rescued by scavenging of oxygen radicals. We show VIT expression is regulated by iron at transcript and protein levels, and by altering VIT localization. In the absence of VIT, T. gondii responds by altering expression of iron metabolism genes and by increasing antioxidant protein catalase activity. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.
EEG repetition and change detection responses in infancy predict adaptive functioning in preschool age: a longitudinal study
Authors: Deguire Florence , López-Arango Gabriela , Knoth Inga Sophia , Côté Valérie , Agbogba Kristian , Lippé Sarah 
Published: June 2023

AbstractNeurodevelopmental disorders (NDDs) are mostly diagnosed around the age of 4–5 years, which is too late considering that the brain is most susceptive to interventions during the first two years of life. Currently, diagnosis of NDDs is based on observed behaviors and symptoms, but identification of objective biomarkers would allow for earlier screening. In this longitudinal study, we investigated the relationship between repetition and change detection responses measured using an EEG oddball task during the first year of life and at two years of age, and cognitive abilities and adaptive functioning during preschool years (4 years old). Identification of early biomarkers is challenging given that there is a lot of variability in developmental courses among young infants. Therefore, the second aim of this study is to assess whether brain growth is a factor of interindividual variability that influences repetition and change detection responses. To obtain variability in brain growth beyond the normative range, infants with macrocephaly were included in our sample. Thus, 43 normocephalic children and 20 macrocephalic children were tested. Cognitive abilities at preschool age were assessed with the WPPSI-IV and adaptive functioning was measured with the ABAS-II. Time–frequency analyses were conducted on the EEG data. Results indicated that repetition and change detection responses in the first year of life predict adaptive functioning at 4 years of age, independently of head circumference. Moreover, our findings suggested that brain growth explains variability in neural responses mostly in the first years of life, so that macrocephalic children did not display repetition suppression responses, while normocephalic children did. This longitudinal study demonstrates that the first year of life is an important period for the early screening of children at risk of developing NDDs.
Transcranial magnetic stimulation of the left middle frontal gyrus modulates the information people communicate in different social contexts
Authors: Martín-Luengo Beatriz , Vorobiova Alicia Nunez , Feurra Matteo , Myachykov Andriy , Shtyrov Yury 
Published: June 2023

AbstractNeocortical structures of the left frontal lobe, middle frontal gyrus (MFG) in particular, have been suggested to be linked to the processing of punishing and unpleasant outcomes in decision tasks. To assess the role of left MFG (lMFG) in communicative decisions, we used repetitive transcranial magnetic stimulation (rTMS) to inhibit its function during communicational exchanges under two types of social contexts: formal and informal. Three groups of participants received an offline 1-Hz inhibitory rTMS of lMFG, right MFG as an active control site, or lMFG sham/placebo TMS as a passive control condition. Participants’ task included answering difficult general-knowledge questions, rating their confidence in their answers’ correctness, and, finally, deciding if they would report or withhold these answers in formal and informal social contexts. There were significantly more reported than withheld answers in the informal context in all groups. The formal context showed no differences between reported and withheld answers in both control conditions, while, crucially, real rTMS of lMFG produced a different pattern, with more withheld than reported answers. Thus, lMFG inhibition seems to result in more rational decisions made only in formal communication contexts, where there is a perception of a certain pressure or possible negative outcomes. In informal social contexts and in the absence of negative consequences the pattern of answers did not change, regardless of the reporting strategy or the TMS protocol used. These results suggest selective context-dependent involvement of the lMFG in decision-making processes during communicational exchanges taking place under social pressure.
Mapping gut parasitism patterns in a cohort of Egyptians
Authors: El-Wakil Eman S. , Zalat Rabab S. , El-Badry Ayman A. 
Published: June 2023

AbstractIn developing countries, the prevalence of intestinal parasitic infection is still significant, particularly due to geographical and socioeconomic variables. The objective of this study was to map the distribution pattern of intestinal parasitic infection in a cohort of the Egyptian population, as well as to assess associated risk factors. A cross-sectional hospital-based study was conducted on 386 patients. A single fecal specimen was collected from the study individual and examined microscopically for the detection of parasitic infection. DNA was extracted from all samples and utilized to amplify Entamoeba histolytica complex species, Cryptosporidium species, Giardia intestinalis assemblages, and Blastocystis species using PCRs. Typing of Cryptosporidium species and Giardia intestinalis assemblages was performed using restriction enzymes RasI and HaeIII respectively. While Blastocystis spp. subtypes (ST) were identified through sequencing of PCR products and phylogenetic analysis. 59.6% (230/386) of the study patients were infected with one or more intestinal parasites, 87.4%; 201/230 of patients had mono-parasitic infections, and 12.6%; 29/230 had multiple-parasitic infections (P < 0.0001). The predominant protozoa were Blastocystis, followed by Entamoeba histolytica complex, and Giardia intestinalis both as mono-parasites and as part of multiple parasites. Molecular assays showed that Blastocystis ST3, Entamoeba dispar, Giardia intestinalis assemblage B, and Cryptosporidium hominis were the most prevalent species. Intestinal parasitic infection was significantly associated with age, gender, residence, and water source. Multi-parasitism showed that residency in a rural area was a risk factor (OR 4.49; 95% CI 1.51–13.37; P = 0.007). Egyptians residing in rural areas have a high prevalence of intestinal multi-parasitism. Therefore, to lessen the prevalence and effects of these infections in this group, effective and sustainable control methods, providing health education focusing on good personal hygiene habits, and providing a safe drinking water supply should be implemented.
TGFβ inhibition and mesenchymal to epithelial transition initiation by Xenopus egg extract: first steps towards early reprogramming in fish somatic cell
Authors: Chênais Nathalie , Le Cam Aurelie , Guillet Brigitte , Lareyre Jean-Jacques , Labbé Catherine 
Published: June 2023

AbstractXenopus egg extract is a powerful material to modify cultured cells fate and to induce cellular reprogramming in mammals. In this study, the response of goldfish fin cells to in vitro exposure to Xenopus egg extract, and subsequent culture, was studied using a cDNA microarray approach, gene ontology and KEGG pathways analyses, and qPCR validation. We observed that several actors of the TGFβ and Wnt/β-catenin signaling pathways, as well as some mesenchymal markers, were inhibited in treated cells, while several epithelial markers were upregulated. This was associated with morphological changes of the cells in culture, suggesting that egg extract drove cultured fin cells towards a mesenchymal-epithelial transition. This indicates that Xenopus egg extract treatment relieved some barriers of somatic reprogramming in fish cells. However, the lack of re-expression of pou2 and nanog pluripotency markers, the absence of DNA methylation remodeling of their promoter region, and the strong decrease in de novo lipid biosynthesis metabolism, indicate that reprogramming was only partial. The observed changes may render these treated cells more suitable for studies on in vivo reprogramming after somatic cell nuclear transfer.
Vulnerability of cocoa-based agroforestry systems to climate change in West Africa
Authors: Ariza-Salamanca Antonio Jesús , Navarro-Cerrillo Rafael M. , Quero-Pérez José L. , Gallardo-Armas Belinda , Crozier Jayne , Stirling Clare , de Sousa Kauê , González-Moreno Pablo 
Published: June 2023

AbstractPrevious research indicates that some important cocoa cultivated areas in West Africa will become unsuitable for growing cocoa in the next decades. However, it is not clear if this change will be mirrored by the shade tree species that could be used in cocoa-based agroforestry systems (C-AFS). We characterized current and future patterns of habitat suitability for 38 tree species (including cocoa), using a consensus method for species distribution modelling considering for the first time climatic and soil variables. The models projected an increase of up to 6% of the potential suitable area for cocoa by 2060 compared to its current suitable area in West Africa. Furthermore, the suitable area was highly reduced (14.5%) once considering only available land-use not contributing to deforestation. Regarding shade trees, 50% of the 37 shade tree species modelled will experience a decrease in geographic rate extent by 2040 in West Africa, and 60% by 2060. Hotspots of shade tree species richness overlap the current core cocoa production areas in Ghana and Côte d’Ivoire, suggesting a potential mismatch for the outer areas in West Africa. Our results highlight the importance of transforming cocoa-based agroforestry systems by changing shade tree species composition to adapt this production systems for future climate conditions.
Stability analysis and selection of sugar beet (Beta vulgaris L.) genotypes using AMMI, BLUP, GGE biplot and MTSI
Authors: Taleghani Dariush , Rajabi Abazar , Saremirad Ali , Fasahat Parviz 
Published: June 2023

AbstractThe methods utilized to analyze genotype by environment interaction (GEI) and assess the stability and adaptability of genotypes are constantly changing and developing. In this regard, often instead of depending on a single analysis, it is better to use a combination of several methods to measure the nature of the GEI from various dimensions. In this study, the GEI was investigated using different methods. For this purpose, 18 sugar beet genotypes were evaluated in randomized complete block design in five research stations over 2 years. The additive effects analysis of the additive main effects and multiplicative interaction (AMMI) model showed that the effects of genotype, environment and GEI were significant for root yield (RY), white sugar yield (WSY), sugar content (SC), and extraction coefficient of sugar (ECS). The multiplicative effect's analysis of AMMI into interaction principal components (IPCs) showed that the number of significant components varies from one to four in the studied traits. According to the biplot of the mean yield against the weighted average of absolute scores (WAAS) of the IPCs, G2 and G16 for RY, G16 and G2 for WSY, G6, G4, and G1 for SC and G8, G10 and G15 for ECS were identified as stable genotypes with optimum performance. The likelihood ratio test showed that the effects of genotype and GEI was significant for all studied traits. In terms of RY and WSY, G3 and G4 had high mean values of the best linear unbiased predictions (BLUP), so they were identified as suitable genotypes. However, in terms of SC and ECS, G15 obtained high mean values of the BLUP. The GGE biplot method classified environments into four (RY and ECS) and three (WSY and SC) mega-environments (MEs). Based on the multi-trait stability index (MTSI), G15, G10, G6, and G1 were the most ideal genotypes.
An oral cancer vaccine using Bifidobacterium vector augments combination of anti-PD-1 and anti-CTLA-4 antibodies in mouse renal cell carcinoma model
Authors: Ueki Hideto , Kitagawa Koichi , Kato Mako , Yanase Shihoko , Okamura Yasuyoshi , Bando Yukari , Hara Takuto , Terakawa Tomoaki , Furukawa Junya , Nakano Yuzo , Fujisawa Masato , Shirakawa Toshiro 
Published: June 2023

AbstractRecently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60–70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.
Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness
Authors: Frohlich Joel , Mediano Pedro A. M. , Bavato Francesco , Gharabaghi Alireza 
Published: June 2023

AbstractLow-frequency (<4 Hz) neural activity, particularly in the delta band, is generally indicative of loss of consciousness and cortical down states, particularly when it is diffuse and high amplitude. Remarkably, however, drug challenge studies of several diverse classes of pharmacological agents—including drugs which treat epilepsy, activate GABABreceptors, block acetylcholine receptors, or produce psychedelic effects—demonstrate neural activity resembling cortical down states even as the participants remain conscious. Of those substances that are safe to use in healthy volunteers, some may be highly valuable research tools for investigating which neural activity patterns are sufficient for consciousness or its absence.
Intrinsic randomness in epidemic modelling beyond statistical uncertainty
Authors: Penn Matthew J. , Laydon Daniel J. , Penn Joseph , Whittaker Charles , Morgenstern Christian , Ratmann Oliver , Mishra Swapnil , Pakkanen Mikko S. , Donnelly Christl A. , Bhatt Samir 
Published: June 2023

AbstractUncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.
Few-femtosecond phase-sensitive detection of infrared electric fields with a third-order nonlinearity
Authors: Kempf Hannes , Sulzer Philipp , Liehl Andreas , Leitenstorfer Alfred , Tenne Ron 
Published: June 2023

AbstractMeasuring an electric field waveform beyond radio frequencies is often accomplished via a second-order nonlinear interaction with a laser pulse shorter than half of the field’s oscillation period. However, synthesizing such a gate pulse is extremely challenging when sampling mid- (MIR) and near- (NIR) infrared transients. Here, we demonstrate an alternative approach: a third-order nonlinear interaction with a relatively long multi-cycle pulse directly retrieves an electric-field transient whose central frequency is 156 THz. A theoretical model, exploring the different nonlinear frequency mixing processes, accurately reproduces our results. Furthermore, we demonstrate a measurement of the real part of a sample’s dielectric function, information that is challenging to retrieve in time-resolved spectroscopy and is therefore often overlooked. Our method paves the way towards experimentally simple MIR-to-NIR time-resolved spectroscopy that simultaneously extracts the spectral amplitude and phase information, an important extension of optical pump-probe spectroscopy of, e.g., molecular vibrations and fundamental excitations in condensed-matter physics.
Superlattice-stabilized structure and charge transfer assisted photoluminescence enhancement in a samarium-doped high entropy perovskite oxide
Authors: Xia Lei , Mao Zhan , Wang Xin , Zhu Jing , Xie Jiyang , Wang Zhe , Hu Wanbiao 
Published: June 2023

A new orange-red-emitting phosphor, A-site Sm3+ doped high-entropy perovskite oxide Ca(Zr0.2Ti0.2Sn0.2Hf0.2Nb0.2)O3 is reported, which brings about superlattice satellites and charge transfer states to exhibit significantly enhanced PL property.