bluuebunny/crossref_metadata_2025 huggingface dataset:
Tyrosinases: a family of copper-containing metalloenzymes
Authors: Pretzler Matthias , Rompel Annette
Published: November 2024

Tyrosinases (TYRs) are a family of copper-containing metalloenzymes that are present in all domains of life. TYRs catalyze the reactions that start the biosynthesis of melanin, the main pigment of the animal kingdom, and are also involved in the formation of the bright colors seen on the caps of mushrooms and in the petals of flowers. TYRs catalyze the ortho-hydroxylation and oxidation of phenols and the oxidation of catechols to the respective o-quinones. They only need molecular oxygen to do that, and the products of TYRs—o-quinones—are highly reactive and will usually react with the next available nucleophile. This reactivity can be harnessed for pharmaceutical applications as well as in environmental and food biotechnology. The majority of both basic and applied research on TYRs utilizes “mushroom tyrosinase”, a crude enzyme preparation derived from button mushroom (Agaricus bisporus) fruiting bodies. Access to pure TYR preparations comes almost exclusively from the production of recombinant TYRs as the purification of these enzymes from the natural source is usually very laborious and plagued by low yields. In this text an introduction into the biochemistry of the enzyme TYR will be given, followed by an overview of available structural data of TYRs, the current model for the catalytic mechanism, a survey of reports on the recombinant production of this important metalloenzyme family, and a review of the applications of TYRs for the synthesis of catechols, as biosensors, in bioremediation, for the cross-linking of proteins and medical hydrogels as well as for melanoma treatment.

Graphical Abstract
ChatGPT as a modern tool for Bible teaching in confessional religious education: a German view
Authors: Chrostowski Mariusz , Najda Andrzej Jacek
Published: November 2024

Biblical didactics is an important element of confessional religious education. In traditional settings, it is primarily associated with working with the text, alone or in groups, in plenary discussion or pantomime. Nowadays, however, young people are increasingly acquiring their knowledge—including about the Bible—on the Internet, using new technologies such as conversational Artificial Intelligence (AI), of which ChatGPT (Generative Pre-trained Transformers) is perhaps the best-known example. In this context, the following article seeks to answer the question of whether, and if so to what extent, ChatGPT can be a helpful tool for teaching the Bible in the classroom. To answer this question, the authors present a theoretical framework that encompasses both foundational insights into conversational AI and ChatGPT, as well as their implications for religious education and biblical teaching in Germany. In the next step, based on J. Theis’ five-step model of Bible didactics [(1) initial perception; (2) analysis of the text; (3) in-depth reflection; (4) critical interpretation; (5) creative assimilation], ways of using ChatGPT in biblical teaching in the classroom are presented and their potential limitations are discussed. The article concludes with six final theses that summarise the investigation findings and offer some suggestions for the future.
Probing the High-Entropy Concept Through the Irradiation Response of Near-Equimolar (CrNbTaTiW)C Ceramic Coatings
Authors: Osinger Barbara , Tunes Matheus A. , Willenshofer Patrick , Greaves Graeme , Ström Petter , Malinovskis Paulius , Vishnyakov Vladimir M. , Lewin Erik , Fritze Stefan
Published: November 2024

High-entropy ceramics have been studied as potential candidates for applications in extreme environments, such as nuclear fusion reactors. Their beneficial properties and increased radiation tolerance are often attributed to their compositional complexity achieved through equimolarity. A near-equimolar (CrNbTaTiW)C carbide, obtained by magnetron sputtering, was investigated using in situ TEM whilst being exposed to 300-keV Xe heavy ion irradiation at 573 K. The material did not show structural changes or amorphisation after irradiation to 8.5 dpa. The pristine material showed partial elemental segregation of Cr and Ti and after irradiation redistribution and homogenisation of the solid solution was observed. Furthermore, the coating showed signs of erosion damage near the surface and along some of the grain boundaries, likely due to sputtering during the energetic particle bombardment. This work suggests the response to irradiation in these novel multicomponent ceramics to be multifaceted—determined by an interplay of composition, microstructure, and constituent elements’ chemistry—going beyond simply equimolarity.
The Normativity of Law
Authors: Giudice Michael
Published: November 2024

In the philosophy of law there has been a proliferation of advanced work in the last thirty years on the normativity of law. Recent theories explore law's character as a special kind of convention, shared cooperative activity, and social artifact, among other perspectives, to explain the precise way in which law provides subjects with reasons for action. Yet, for all their sophistication, such accounts fail to deliver on their promise, which is to establish how law creates more than just legal reasons for action. This Element aims to survey these views and others, situate them in a broader context of theories about the nature of law, and subsequently suggest a path forward based on the methodological continuity between analytical, evaluative, and empirical approaches to law's normativity.
Reflective Practice for Early Career Language Teachers
Authors: Farrell Thomas S. C.
Published: November 2024

Based on a range of detailed case studies, this innovative book presents a model for early career language teacher development. It showcases the lived experiences of English language teachers in their training years, as well as the reflections of two more experienced English language teachers, and uses these case studies to provide practical guidelines on early career needs and development. It outlines four essential and highly connected conditions that will enable teachers to survive and thrive in the profession: reflection, support, resilience, and well-being. Using an innovative, evidence-based, data-informed approach to reflective practice, the book covers teachers' philosophy, principles, theory, practice, and critical reflection beyond practice. Each chapter contains practical reflection activities, to encourage reflection throughout from the reader on what the research reveals. It is essential reading for graduate students who are training to become language teachers, as well as language teacher trainers and lecturers.
Literacies of Migration
Authors: Smith Patriann
Published: November 2024

Drawing on the lived experiences of high school-aged young Black immigrants, this book paints imaginaries of racialized translanguaging and transsemiotizing, leveraged transnationally by teenagers across the Caribbean and the United States. The Black Caribbean youth reflect a full range of literacy practices – six distinct holistic literacies – identified as a basis for flourishing. These literacies of migration encapsulate numerous examples of how the youth are racialized transgeographically, based on their translanguaging and transsemiotizing with Englishes, both institutionally and individually. In turn, the book advances a heuristic of semiolingual innocence containing eight elements, informed by the Black immigrant literacies of Caribbean youth. Through the eight elements presented – flourishing, purpose, comfort, expansion, paradox, originality, interdependence, and imagination – stakeholders and systems will be positioned to better understand and address the urgent needs of these youth. Ultimately, the heuristic supports a reinscribing of semiolingual innocence for Black Caribbean immigrant and transnational youth, as well as for all youth.
Effects of Mesoscale Eddies on Southern Ocean Biogeochemistry
Authors: Keppler Lydia , Eddebbar Yassir A. , Gille Sarah T. , Guisewhite Nicola , Mazloff Matthew R. , Tamsitt Veronica , Verdy Ariane , Talley Lynne D.
Published: November 2024

The Southern Ocean is rich in highly dynamic mesoscale eddies and substantially modulates global biogeochemical cycles. However, the overall surface and subsurface effects of eddies on the Southern Ocean biogeochemistry have not been quantified observationally at a large scale. Here, we co‐locate eddies, identified in the Meta3.2DT satellite altimeter‐based product, with biogeochemical Argo floats to determine the effects of eddies on the dissolved inorganic carbon (DIC), nitrate, and dissolved oxygen concentrations in the upper 1,500 m of the ice‐free Southern Ocean, as well as the eddy effects on the carbon fluxes in this region. DIC and nitrate concentrations are lower in anticyclonic eddies (AEs) and increased in cyclonic eddies (CEs), while dissolved oxygen anomalies switch signs above (CEs: positive, AEs: negative) and below the mixed layer (CEs: negative, AEs: positive). We attribute these anomalies primarily to eddy pumping (isopycnal heave), as well as eddy trapping for oxygen. Maximum anomalies in all tracers occur at greater depths in the subduction zone north of the Antarctic Circumpolar Current (ACC) compared to the upwelling region in the ACC, reflecting differences in background vertical structures. Eddy effects on air–sea exchange have significant seasonal variability, with additional outgassing in CEs in fall (physical process) and additional oceanic uptake in AEs and CEs in spring (biological and physical process). Integrated over the Southern Ocean, AEs contribute 0.01 Pg C (7 ) to the Southern Ocean carbon uptake, and CEs offset this by 0.01 Pg C (2 ). These findings underscore the importance of considering eddy impacts in observing networks and climate models.
Effect of Regional Housing Hardship on Spatial Variation in Cancer Incidence: Does Housing Stress Increase Cancer Incidence?
Authors: Yu Haishi , Huang Jinyu , Wang Yang , Yue Xiaoli , Wu Yingmei , Zhang Hong'ou
Published: November 2024

Housing hardship can create a range of health issues. However, little attention has been paid to the relationship between housing hardship and cancer incidence. This study examines the Yangtze River Economic Belt (YREB) in China as a case study to develop a model of factors related to housing hardship that can affect cancer incidence. This study employs spatial regression models to investigate the correlation between housing hardship and cancer incidence and further explores the variation in the correlation between urban areas (UAs) and non‐urban areas (NUAs). The research conclusions are as follows: (a) a palpable correlation exists between housing hardship and cancer incidence. The housing price‐to‐income ratio (HPIR) and the rental household proportion (RHP) are positively correlated to cancer incidence, whereas the per capita living area (PCLA) has a negative correlation with cancer incidence. (b) The differences in the impact of housing hardship on cancer incidence between the UAs and the NUAs are reflected mainly in the differences in the PCLA and the RHP. The PCLA has a strong association with cancer incidence in the UAs, whereas the RHP demonstrates a strong correlation with cancer incidence in the NUAs. (c) Significant spatial heterogeneity is observed in housing hardship in the YREB.
Weakened and Lowered Sensitivity of Extreme Precipitation Over the Global Land Monsoon Regions During the Last Glacial Maximum
Authors: Kong Xiaohan , Yan Qing , Wei Ting
Published: November 2024

The Last Glacial Maximum (LGM) provides an opportunity to estimate how extreme precipitation may respond to large radiative forcing and hence the constraints for its future behavior. Using daily outputs from the Paleoclimate Modeling Intercomparison Project, we illustrate a decrease in extreme precipitation intensity over the global monsoon regions during the LGM relative to preindustrial, accompanied by increased extreme precipitation frequency, although regional differences exist. The weakened extreme precipitation is dominated by the thermodynamics (∼92%) linked to change in temperature, with the dynamic component linked to change in vertical velocity contributing to regional differences. Furthermore, we show a ∼3.6% decrease in extreme precipitation per 1°C cooling during the LGM, lower than the sensitivity (∼5%/°C) in future warming scenarios. Our results are in line with the proxies‐based drier conditions and lower equilibrium climate sensitivity during the LGM, and may advance understanding of extreme precipitation variation in a warmer future.
Attribution of the Record‐Breaking Extreme Cold Event Over Northern East Asia in December 2023
Authors: Gong Hainan , Ma Kangjie , Wang Lin , Chen Wen
Published: November 2024

Against the backdrop of global warming, Northern East Asia experienced a record‐breaking extreme cold event during December 13 to 19 in 2023. The mechanisms behind this extreme cold event remain unclear. This study uses the circulation projection method to detect and quantify the contributions of various factors to this extreme cold event. The findings indicate that large‐scale atmospheric circulation anomalies are the predominant factors triggering this cold wave. The Polar‐Eurasian (POL)‐like teleconnection pattern is identified as a key driver for the cold anomalies, contributing approximately 85% of total cold anomalies in Northern East Asia in this event. Although the POL‐like teleconnection is largely internally generated, the preceding low sea ice levels in the Barents and Kara Seas can strengthen and maintain POL teleconnection. Additionally, preceding November increased snow cover in Northern East Asia can further amplify this cold event by enhancing local surface albedo and reducing incoming solar shortwave radiation.
Sorting and Weathering Trends of Soil at Gale Crater, Mars: Implications for Regional Pedological Processes
Authors: Shi Yutong , Zhao Siyuan , Karunatillake Suniti , Cousin Agnes , Zhao Jiannan , Xiao Long
Published: November 2024

Detailed soil characterization at Gale crater based on in situ observations has revealed compositional trends within soils, while the physical and chemical processes underlying the compositional trends remain to be evaluated. Here we use the grain‐morphometrical and geochemical trends across the Wentworth‐classes of 48 in situ soil targets at Gale crater to evaluate underlying pedological processes and potential chemical weathering signatures. The concentration of olivine minerals within the ∼250 to ∼500 μm size range indicates the prevalence of heavy mineral sorting in a granulometric sense in Gale soils that surpasses the possible effect of the cratering‐induced mixing processes. The extent of olivine sorting in soils varies spatially and is influenced by the targets' aeolian setting. The finest portion of Gale soils (<125 μm) is likely a mixture of allochthonous sediment, globally sourced from atmospheric suspension, and autochthonous counterparts from the weathering of local rocks, while the coarser soils (>125 μm) are mostly sourced from local rocks, with possible inputs from both the unaltered parent rock of the Stimson formation and the bedrocks that have undergone diagenetic alteration. If applicable globally, this would reinforce prior inferences that even dust‐mantled regions are geochemically heterogeneous owing to a substantial fraction of soils derived from underlying lithology. The low chemical weathering intensity and coupling of mobile elements in soils suggest localized, low pH and low water‐to‐rock ratio aqueous weathering conditions under predominantly cold and arid climates, which may occur either during post‐pedogenetic alteration in soils or during the acidic alteration of source rocks.
Improving Prediction of Marine Low Clouds Using Cloud Droplet Number Concentration in a Convolutional Neural Network
Authors: Cao Yang , Zhu Yannian , Wang Minghuai , Rosenfeld Daniel , Zhou Chen , Liu Jihu , Liang Yuan , Huang Kang‐En , Wang Quan , Bai Heming , Wang Yichuan , Wang Hao , Zhang Haipeng
Published: November 2024

Marine low clouds play a crucial role in cooling the climate, but accurately predicting them remains challenging due to their highly non‐linear response to various factors. Previous studies usually overlook the effects of cloud droplet number concentration (Nd) and the non‐local information of the target grids. To address these challenges, we introduce a convolutional neural network model (CNNMet‐Nd) that uses both local and non‐local information and includes Nd as a cloud‐controlling factor to enhance the predictive ability of daily cloud cover, albedo, and cloud radiative effects (CRE) for global marine low clouds. CNNMet‐Nd demonstrates superior performance, explaining over 70% of the variance in these three cloud variables for scenes of 1° × 1°, a notable improvement over past efforts. CNNMet‐Nd also accurately replicates geographical patterns of trends in marine low clouds from 2003 to 2022. In contrast, a similar model without Nd (CNNMet) struggles to predict long‐term trends in cloud properties effectively. Permutation importance analysis further highlights the critical role of Nd in CNNMet‐N's predictive success. Further comparisons with an artificial neural network (ANNMet‐Nd) model, which uses the same inputs but without considering spatial dependence, show CNNMet‐Nd's superior performance with R2 values for cloud cover, albedo, and CRE being 0.16, 0.12, and 0.18 higher, respectively. This highlights the importance of incorporating non‐local information, at least on a daily scale, into low cloud predictions to enhance climate model parameterizations.
Imaging of the Ionosphere and Plasmasphere Using GNSS Slant TEC Obtained From LEO Satellites
Authors: Schreiter Lucas , Brack Andreas , Männel Benjamin , Schuh Harald , Arnold Daniel , Jäggi Adrian
Published: November 2024

Satellites with dual‐frequency Global Navigation Satellite Systems (GNSS) receivers can measure integrated electron density, known as slant Total Electron Content (sTEC), between the receiver and transmitter. Precise relative variations of sTEC are achievable using phase measurements on L1 and L2 frequencies, yielding an accuracy of around 0.1 TECU or better. However, CubeSats like Spire LEMUR, with simpler setups (e.g., patch antennas) and code noise in the order of several meters, face limitations in accuracy. Their precision, determined by phase observations, remains in the 0.1–0.3 TECU range. With a substantial number of observations and comprehensive coverage of lines of sight between Low Earth Orbit (LEO) and GNSS satellites, global electron density can be reconstructed from sTEC measurements. Utilizing 27 satellites from various missions, including Swarm, Gravity Recovery And Climate Experiment Follow‐On, Jason‐3, Sentinel 1/2/3, COSMIC‐2, and Spire CubeSats, a cubic B‐spline expansion in magnetic latitude, magnetic local time, and altitude is employed to model the logarithmic electron density. Hourly snapshots of the three‐dimensional electron density are generated, adjusting the model parameters through non‐linear least squares based on sTEC observations. Results demonstrate that including Spire significantly enhances estimates, showcasing exceptional agreement with in situ observations from Swarm and Defense Meteorological Satellite Program LEO satellites. The model outperforms contemporary climatological models, such as International Reference Ionosphere (IRI)‐2020 and the neural network‐based NET model. Validation efforts include comparisons with ground‐based sTEC measurements, space‐based vertical TEC from Jason‐3 altimetry, and global TEC maps from the Center for Orbit Determination in Europe and the German Research Center for Geosciences (GFZ).
The Growth and Decay of Intense GNSS Amplitude and Phase Scintillation During Non‐Storm Conditions
Authors: Madhanakumar Mahith , Spicher Andres , Vierinen Juha , Oksavik Kjellmar , Coster Anthea J. , Huyghebaert Devin Ray , Martin Carley J. , Häggström Ingemar , Paxton Larry J.
Published: November 2024

A multi‐instrument study is conducted at the dayside polar ionosphere to investigate the spatio‐temporal evolution of scintillation in Global Navigation Satellite System (GNSS) signals during non‐storm conditions. Bursts of intense amplitude and phase scintillation started to occur at 9 MLT and persisted for more than 1 hour implying the simultaneous existence of Fresnel and large‐scale sized irregularities of significant strength in the pre‐noon sector. Measurements from the EISCAT radar in Svalbard (ESR) revealed the presence of dense plasma structures with significant gradients in regions of strong Joule heating/fast flows and soft precipitation when scintillation was enhanced. Plasma structuring down to Fresnel scales were observed both in the auroral oval as well as inside the polar cap with the associated amplitude scintillation exhibiting similar strengths regardless of whether the density structures were in regions of active auroral dynamics or not. The observations are placed within the context of different sources of free energy, providing insights into the important mechanisms that generate irregularities capable of perturbing GNSS signal properties in the dayside ionosphere. Furthermore, a strong negative excursion in the interplanetary magnetic field (IMF) component during the northward turning of led to the transport of a depleted region of plasma density into the post‐noon sector that significantly weakened both amplitude and phase scintillation.
Comparison of nasal microbiota between preterm and full-term infants in early life
Authors: Gorlanova Olga , Nissen-Kratzert Annika , Mostacci Nadja , Rüttimann Céline , Künstle Noemi , Marten Andrea , Gisler Amanda , Bacher Katharina , Decrue Fabienne , Salem Yasmin , Usemann Jakob , Korten Insa , Yammine Sophie , Nahum Uri , Schulzke Sven , Latzin Philipp , Röösli Martin , Fuchs Oliver ,   BILD study consortium, Beck Fiona , Bovermann Xenia , Casaulta Carmen , Curdy Marion , Sena Carla Rebeca Da Silva , de Hoogh Kees , Frauchiger Bettina , Frey Urs , Gorlanova Olga , Dac Léa Kim-Mi Ho , Kieninger Elisabeth , Korten Insa , Künstle Noëmi , Latzin Philipp , Marten Andrea , Müller Loretta , Nahum Uri , Oestreich Marc-Alexander , Röösli Martin , Rüttimann Céline , Schulzke Sven , Sinues Pablo , Steinberg Ruth , Stöcklin Benjamin , Streibel Carmen , Usemann Jakob , Wyler Florian , Yammine Sophie , Hilty Markus , Frey Urs
Published: November 2024

Background

The respiratory microbiota influences infant immune system maturation. Little is known about how perinatal, physiological, and environmental exposures impact the nasal microbiota in preterm infants after discharge, or nasal microbiota differences between preterm and healthy full-term infants.

Methods

Nasal swabs (from 136 preterm and 299 full-term infants at mean postmenstrual age of 45 weeks from the prospective Basel-Bern Infant Lung Development cohort) were analyzed by 16S-rRNA gene amplification and sequencing (Illumina MiSeq). Associations were tested with multivariable linear regression and principal coordinate analysis.

Results

Presence of older siblings in preterm infants was associated with β-diversity (PERMANOVA p = 0.001) and an increased abundance of Moraxella and Haemophilus. The nasal microbiota of preterm infants exhibited a distinct composition compared to that of full-term infants (PERMANOVA, R2 = 0.014, p = 0.001), characterized by a reduced abundance of the Moraxella and Dolosigranulum genera (ANCOM-BC, p < 0.05).

Conclusion

Our results indicate that, despite both infant groups having similar nasal microbiota patterns, there are some disparities which suggest that prematurity influences the initial microbiota colonization. In preterm infants the presence of older siblings had an effect on the nasal microbiota, whereas perinatal and early postnatal factors did not show significant effects.

Impact

Presence of older siblings affected the nasal microbiota of preterm infants.

This study demonstrated that microbiota composition differs between full-term and preterm infants, with a lower abundance of Moraxella and Dolosigranulum in preterm infants.

Examining the differences in nasal microbiota between preterm and full-term infants may contribute to understanding the trajectory of the bacterial component of the nasal microbiota of preterm infants.
Oral health-related quality of life in Egyptian children with Molar Incisor Hypomineralisation. An observational study
Authors: Gadallah Lamia Khairy , Korayem Eman , Wahby Reem
Published: November 2024

Aim

The aim of this study was to study the effect of Molar Incisor Hypomineralisation (MIH) on Oral Health-Related Quality of Life (OHRQoL) in children at the mixed dentition stage and correlate it with their caries experience.

Subjects and methods

One hundred two children aged from 8 to 10 years were recruited, 51 with MIH and 51 as control. Caries experience was recorded using DMFT/deft and ICDAS II. MIH-TNI index was used for classifying MIH severity. CPQ8–10 with its Arabic version was used to evaluate OHRQoL. Mann–Whitney U test and Kruskal–Wallis test were used for comparisons (p ≤ 0.05).

Results

The mean value for CPQ8–10 in MIH group was 24.67 (±11.84; median 23; range 6–55) in comparison to 21.04 (±12.3; median 18; range 2–54) for the control group, with no significant difference between groups (p = 0.109). A significantly higher value (p = 0.011) was recorded in patients with MIH-TNI 4 mean 32.16 (±13.9; median 35; range from 7 to 55) in comparison to other categories of MIH.

Conclusion

Children with and without MIH, with similar caries experience showed no difference in OHRQoL. However, the presence of the severe form of MIH including hypersensitivity and enamel disintegration negatively impacted those children’s OHRQoL.
A novel AI-based score for assessing the prognostic value of intra-epithelial lymphocytes in oral epithelial dysplasia
Authors: Shephard Adam J. , Mahmood Hanya , Raza Shan E. Ahmed , Khurram Syed Ali , Rajpoot Nasir M.
Published: November 2024

Background

Oral epithelial dysplasia (OED) poses a significant clinical challenge due to its potential for malignant transformation and the lack of reliable prognostic markers. Current OED grading systems do not reliably predict transformation and suffer from considerable observer variability. Recent studies have highlighted that peri-epithelial lymphocytes may play an important role in OED malignant transformation, with indication that intra-epithelial lymphocytes (IELs) may also be important.

Methods

We propose a novel artificial intelligence (AI) based IEL score from Haematoxylin and Eosin (H&E) stained Whole Slide Images (WSIs) of OED tissue slides. We determine the prognostic value of our IEL score on a digital dataset of 219 OED WSIs (acquired using three different scanners), compared to pathologist-led clinical grading.

Results

Our IEL scores demonstrated significant prognostic value (C-index = 0.67, p < 0.001) and were shown to improve both the binary/WHO grading systems in multivariate analyses (p < 0.001). Nuclear analyses confirmed the positive association between higher IEL scores, more severe OED and malignant transformation (p < 0.05).

Conclusions

This underscores the potential importance of IELs, and by extension our IEL score, as prognostic indicators in OED. Further validation through prospective multi-centric studies is warranted to confirm the clinical utility of IELs.
High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML)
Authors: Bajrami Saipi Mihada , Ruiba Alessia , Schittenhelm Marcus Matthias , Blumenstock Gunnar , Győrffy Balázs , Fazio Serena , Hafner Marlon , Ahrens Anna-Lena , Aldinger Lara , Aellig Vanessa , Kavelaars François G. , Nombela-Arrieta César , Fend Falko , Valk Peter J. M. , Christoph Driessen , Kampa-Schittenhelm Kerstin Maria
Published: November 2024

Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome. Four independent patient cohorts comprising about 1500 patient samples were analysed and consistently confirm an association of high iASPP expression with unfavourable clinical characteristics and shorter survival. Notably, the predictive role of iASPP is independent of, and adds information to, the European LeukemiaNET (ELN) risk classification. iASPP-interference cell models were developed to investigate the underlying functional aspects of iASPP in AML biology. Attenuation of iASPP expression resulted in reduced proliferation rates of leukemic blasts and rendered cells more susceptible towards induction of apoptosis in response to cytotoxic therapy. In line, independent NSG xenograft mouse experiments demonstrate that attenuation of iASPP results in a significant delay of disease onset and tumor burden and this translates to longer overall survival of mice. In conclusion, deregulation of iASPP has direct functional consequences in AML. Determination of iASPP expression levels provides valuable additional information as a predictive marker in AML and may guide treatment decisions.
A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis
Authors: Guo Zeyi , Li Zhongzhe , Guo Jinhao , Gan Luxiang , Mo Haiyu , Zhang Jiajun , Fu Yu , Wang Yi , Jin Meixian , Wu Yanping , Xie Qingyu , Tan Kunjiang , Wang Chunming , Xu Yuyan , He Guolin , Cai Lei , Gao Yi , Pan Mingxin , Fu Shunjun
Published: November 2024

Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway. To investigate the upstream regulatory mechanism, the results from RNA Immunoprecipitation and RNA pull-down indicated that the specific region of circIPP2A2 interacted with Hornerin. Additionally, patients with circIPP2A2 upregulation exhibited a poorer survival outcome following surgery compared to the cases with downregulated circIPP2A2. After the structure verification of circIPP2A2, loss-of-function studies using a lentiviral vector revealed that circIPP2A2 downregulation significantly inhibited HCC tumorigenesis and progression both in vitro and in vivo. Mechanistically, the m7G-MeRIP results demonstrated significant enrichment of circIPP2A2. Subsequent studies validated that METTL1 influenced the stability of circIPP2A2 and its binding affinity with Hornerin. Immunoprecipitation and immunofluorescence indicated that circIPP2A2 served as a molecular scaffold to facilitate Hornerin to interact with PI3K. In conclusion, our findings reveal that circIPP2A2, regulated by N7-methylguanosine modification, promotes malignant behaviors in HCC by serving as a molecular scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis. Targeting circIPP2A2 may be a promising therapeutic strategy for patients with HCC.
A wide range of chromosome numbers result from unreduced gamete production in Brassica juncea × B. napus (AABC) interspecific hybrids
Authors: Addo Nyarko Charles , Katche Elvis , Báez Mariana , Lv Zhenling , Mason Annaliese S.
Published: November 2024

The establishment of successful interspecies hybrids requires restoration of a stable “2n” chromosome complement which can produce viable “n” gametes. This may occur (rarely) via recombination between non-homologous chromosomes, or more commonly is associated with a doubling of parental chromosome number to produce new homologous pairing partners in the hybrid. The production of unreduced “2n” gametes (gametes with the somatic chromosome number) may therefore be evolutionarily useful by serving as a key pathway for the formation of new polyploid hybrids, as might specific mechanisms permitting recombination between non-homologous chromosomes. Here, we investigated chromosome complements and fertility in third generation interspecific hybrids (AABC) resulting from a cross between allopolyploids Brassica juncea (AABB) × B. napus (AACC) followed by self-pollination for two generations. Chromosome numbers ranged from 2n = 48–74 in the experimental population (35 plants), with 9–16 B genome chromosomes and up to 4 copies of A genome chromosomes. Unreduced gamete production leading to a putative genome structure of approximately AAAABBCC was hence predicted to explain the high chromosome numbers observed. Additionally, the estimation of nuclei number in post-meiotic sporads revealed a higher frequency of unreduced gametes (0.04–5.21%) in the third generation AABC interspecific hybrids compared to the parental Brassica juncea (0.07%) and B. napus (0.13%). Our results suggest that unreduced gamete production in the subsequent generations following interspecific hybridization events may play a critical role in restoration of more stable, fertile chromosome complements.
Approaches to investigate tissue-resident innate lymphocytes metabolism at the single-cell level
Authors: Corkish Carrie , Aguiar Cristhiane Favero , Finlay David K.
Published: November 2024

Tissue-resident innate immune cells have important functions in both homeostasis and pathological states. Despite advances in the field, analyzing the metabolism of tissue-resident innate lymphocytes is still challenging. The small number of tissue-resident innate lymphocytes such as ILC, NK, iNKT and γδ T cells poses additional obstacles in their metabolic studies. In this review, we summarize the current understanding of innate lymphocyte metabolism and discuss potential pitfalls associated with the current methodology relying predominantly on in vitro cultured cells or bulk-level comparison. Meanwhile, we also summarize and advocate for the development and adoption of single-cell metabolic assays to accurately profile the metabolism of tissue-resident immune cells directly ex vivo.
Origin of competing charge density waves in kagome metal ScV6Sn6
Authors: Wang Kang , Chen Siyu , Kim Sun-Woo , Monserrat Bartomeu
Published: November 2024

Understanding competing charge density wave (CDW) orders in the bilayer kagome metal ScV6Sn6 remains challenging. Experimentally, upon cooling, short-range order with wave vector $${{{{\bf{q}}}}}_{2}=(\frac{1}{3},\frac{1}{3},\frac{1}{2})$$

q

2

=

(

1

3

,

1

3

,

1

2

)

forms, which is subsequently suppressed by the condensation of long-range $${{{{\bf{q}}}}}_{3}=(\frac{1}{3},\frac{1}{3},\frac{1}{3})$$

q

3

=

(

1

3

,

1

3

,

1

3

)

CDW order at lower temperature. Theoretically, however, the q2 CDW is predicted as the ground state, leaving the CDW mechanism elusive. Here, using anharmonic phonon-phonon calculations combined with density functional theory, we predict a temperature-driven structural phase transitions from the high-temperature pristine phase to the q2 CDW, followed by the low-temperature q3 CDW, explaining experimental observations. We demonstrate that semi-core electron states stabilize the q3 CDW over the q2 CDW. Furthermore, we find that the out-of-plane lattice parameter controls the competing CDWs, motivating us to propose compressive bi-axial strain as an experimental protocol to stabilize the q2 CDW. Finally, we suggest Ge or Pb doping at the Sn site as another potential avenue to control CDW instabilities. Our work provides a full theory of CDWs in ScV6Sn6, rationalizing experimental observations and resolving earlier discrepancies between theory and experiment.
SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections
Authors: Rosenheim Joshua , Gupta Rishi K. , Thakker Clare , Mann Tiffeney , Bell Lucy C. K. , Broderick Claire M. , Madon Kieran , Papargyris Loukas , Dayananda Pete , Kwok Andrew J. , Greenan-Barrett James , Wagstaffe Helen R. , Conibear Emily , Fenn Joe , Hakki Seran , Lindeboom Rik G. H. , Dratva Lisa M. , Lemetais Briac , Weight Caroline M. , Venturini Cristina , Kaforou Myrsini , Levin Michael , Kalinova Mariya , Mann Alex J. , Catchpole Andrew , Knight Julian C. , Nikolić Marko Z. , Teichmann Sarah A. , Killingley Ben , Barclay Wendy , Chain Benjamin M. , Lalvani Ajit , Heyderman Robert S. , Chiu Christopher , Noursadeghi Mahdad
Published: November 2024

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.
Subtilase SBT5.2 inactivates flagellin immunogenicity in the plant apoplast
Authors: Buscaill Pierre , Sanguankiattichai Nattapong , Kaschani Farnusch , Huang Jie , Mooney Brian C. , Li Yuge , Lyu Joy , Sueldo Daniela , Kaiser Markus , van der Hoorn Renier A. L.
Published: November 2024

Most angiosperm plants recognise the 22-residue flagellin (flg22) epitope in bacterial flagellin via homologs of cell surface receptor FLS2 (flagellin sensitive-2) and mount pattern-triggered immune responses. However, flg22 is buried within the flagellin protein indicating that proteases might be required for flg22 release. Here, we demonstrate the extracellular subtilase SBT5.2 not only releases flg22, but also inactivates the immunogenicity of flagellin and flg22 by cleaving within the flg22 epitope, consistent with previous reports that flg22 is unstable in the apoplast. The prolonged lifetime of flg22 in sbt5.2 mutant plants results in increased bacterial immunity in priming assays, indicating that SBT5.2 counterbalances flagellin immunogenicity to provide spatial-temporal control and restrict costly immune responses and that bacteria take advantage of the host proteolytic machinery to avoid detection by flagellin having a protease-sensitive flg22 epitope.
A single nanophotonic platform for producing circularly polarized white light from non-chiral emitters
Authors: Mendoza-Carreño Jose , Bertucci Simone , Garbarino Mauro , Cirignano Matilde , Fiorito Sergio , Lova Paola , Garriga Miquel , Alonso Maria Isabel , Di Stasio Francesco , Mihi Agustín
Published: November 2024

Direct manipulation of light spin-angular momentum is desired in optoelectronic applications such as, displays, telecommunications, or imaging. Generating polarized light from luminophores avoids using optical components that cause brightness losses and hamper on-chip integration of light sources. Endowing chirality to achiral emitters for direct generation of polarized light benefits from existing materials and can be achieved by chiral nanophotonics. However, most chiral nanostructures operate in narrow wavelength ranges and involve nanofabrication processes incompatible with high-throughput production. Here, a single nanophotonic architecture is designed to sustain chiroptical resonances along the visible spectrum. This platform, fabricated with scalable soft-nanoimprint lithography transfers its chirality to conventional emitters (CdSe/CdS nanoplatelets, CdSe/CdS quantum dots, CsPbBr3, CsPbI3 perovskite nanocrystals and F8BT) placed atop, achieving a high dissymmetry emission factor (glum > 1). The dynamics study suggests enhanced out-coupling efficiency for one helicity by the photonic structure. Finally, a white light-emitting blend containing different emitters shows simultaneous dissymmetric emission values along the visible spectrum with this chiral nanophotonic platform.
Immune digital twins for complex human pathologies: applications, limitations, and challenges
Authors: Niarakis Anna , Laubenbacher Reinhard , An Gary , Ilan Yaron , Fisher Jasmin , Flobak Åsmund , Reiche Kristin , Rodríguez Martínez María , Geris Liesbet , Ladeira Luiz , Veschini Lorenzo , Blinov Michael L. , Messina Francesco , Fonseca Luis L. , Ferreira Sandra , Montagud Arnau , Noël Vincent , Marku Malvina , Tsirvouli Eirini , Torres Marcella M. , Harris Leonard A. , Sego T. J. , Cockrell Chase , Shick Amanda E. , Balci Hasan , Salazar Albin , Rian Kinza , Hemedan Ahmed Abdelmonem , Esteban-Medina Marina , Staumont Bernard , Hernandez-Vargas Esteban , Martis B Shiny , Madrid-Valiente Alejandro , Karampelesis Panagiotis , Sordo Vieira Luis , Harlapur Pradyumna , Kulesza Alexander , Nikaein Niloofar , Garira Winston , Malik Sheriff Rahuman S. , Thakar Juilee , Tran Van Du T. , Carbonell-Caballero Jose , Safaei Soroush , Valencia Alfonso , Zinovyev Andrei , Glazier James A.
Published: November 2024

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as “proof of concept” regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality.
Microarray integrated spatial transcriptomics (MIST) for affordable and robust digital pathology
Authors: Juwayria  , Shrivastava Priyansh , Yadav Kaustar , Das Sourabh , Mittal Shubham , Kumar Sunil , Jain Deepali , Malik Prabhat Singh , Gupta Ishaan
Published: November 2024

10X Visium, a popular Spatial transcriptomics (ST) method, faces limited adoption due to its high cost and restricted sample usage per slide. To address these issues, we propose Microarray Integrated Spatial Transcriptomics (MIST), combining conventional tissue microarray (TMA) with Visium, using laser-cutting and 3D printing to enhance slide throughput. Our design facilitates independent replication and customization in individual labs to suit specific experimental needs. We provide a step-by-step guide from designing TMAs to the library preparation step. We demonstrate MIST’s cost-effectiveness and technical benefits over Visium and GeoMx Nanostring. We also introduce ‘AnnotateMap’, a novel computational tool for efficient analysis of multiple ROIs processed through MIST.
A global patent dataset of bioeconomy-related inventions
Authors: Kriesch Lukas , Losacker Sebastian
Published: November 2024

Many governments worldwide have proposed transitioning from a fossil-based economy to a bioeconomy to address climate change, resource depletion, and other environmental concerns. The bioeconomy utilizes renewable biological resources across all sectors and is strongly founded on scientific advances and technological progress. Given that the bioeconomy spans multiple sectors, industries, and technological fields, tracking it is challenging, and both policymakers and researchers lack a comprehensive understanding of the bioeconomy transition’s progress. We aim to solve this problem by providing a dataset on patents, a commonly used indicator to study the development of novel knowledge and technological change, that identifies bioeconomy-related inventions. We leverage the advanced semantic understanding embedded in pre-trained transformer models to identify bioeconomy-related patents based on patent abstracts, and we use a topic modelling approach to identify several coherent technological fields within the corpus of bioeconomy patents. The dataset can be linked to other patent databases and therefore provides rich opportunities to study the technological knowledge base of the bioeconomy.
Deep phenotyping the right ventricle to establish translational MRI biomarkers for characterization of adaptive and maladaptive states in pulmonary hypertension
Authors: Baxan Nicoleta , Zhao Lin , Ashek Ali , Niglas Marili , Wang Dingyi , Khassafi Fatemeh , Sabrin Farah , Dubois Olivier , Chen Chien-Nien , Pullamsetti Soni Savai , Wilkins Martin , Zhao Lan
Published: November 2024

Deep phenotyping the right ventricle (RV) is essential for understanding the mechanisms of adaptive and maladaptive RV responses to pulmonary hypertension (PH). In this study, feature selection coupled with machine learning classification/ranking of specific cardiac magnetic resonance imaging (MRI) features from cine-MRI, flow-sensitized, and extracellular-volume techniques were used to assess RV remodelling in monocrotaline (MCT) and Sugen hypoxia (SuHx) PH rats. Early physiological changes associated with RV adaptation were detected along with prediction of RV maladaptive outcomes. Key adaptation features included haemodynamic alterations of pulmonary blood flow ejection and wave reflection, mild RV dilatation, progressive RV hypertrophy with subtle extracellular volume growth of RV wall. A dominant component of maladaptation was the extracellular matrix increase at RV insertion points and septum, observations compatible with histopathologic and RNA-sequencing results. The upregulation of mammalian target of rapamycin (mTOR) paralleled by AMP-activated protein kinase (AMPK) deactivation was seen at 4-week MCT and 8-week SuHx, along with reduced sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA2) expression, strongly associated with the RV systolic malfunction seen at this stage in vivo. The here established MRI features can serve as potential imaging biomarkers to evaluate PH treatment efficacy in preclinical studies and build up translational markers for the PH clinic.