bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive plant species interact with drought to shift key functions and families in the native rhizosphere
Authors: Ettinger Cassandra L. , LaForgia Marina L.
Published: September 2023

Background and aims

Interactions between species invasions and climate change have the potential to drive changes in plant communities more than either factor alone. One pathway through which these effects can occur is via changes to the rhizosphere microbial community. Invasive plants can alter these microbial communities affecting natives’ abilities to compete with invaders. At the same time, climate change is leading to more frequent extreme wet and dry events. Understanding the response of plant communities to these combined global change drivers requires a comprehensive approach that assesses the relationship between plant competition and belowground rhizosphere microbial community responses.

Methods

Here we use a field experiment in a California grassland with a set of six native annual forbs (i.e., wildflowers) and three invasive annual grasses to test how competition with invasive plants alters both identity and function in the native rhizosphere microbiome, and whether competition between these groups interacts with rainfall to amplify or ameliorate microbial shifts.

Results

Metagenomics of rhizosphere communities revealed that drought combined with competition from invaders altered a higher number of functions and families in the native rhizosphere compared to invasive competition alone or drought alone. Watering combined with invasion led to fewer shifts.

Conclusion

This suggests invasion-driven shifts in the microbial community may be involved in weakening natives’ ability to cope with climate change, especially drought. Understanding the role of the microbial community under invasion and climate change may be critical to mitigating the negative effects of these interacting global change drivers on native communities.

Graphical abstract

Understanding plant community response to global change drivers requires a comprehensive approach that assesses the relationship between plant competition and belowground rhizosphere microbial community responses. (a) In this work, we use a field experiment in a California grassland with a set of native forbs (purple) and invasive grasses (teal) to assess the combined effects of competition and water availability (drought, control, watered) on the rhizosphere microbiome. (b) Drought combined with competition from invaders altered the relative abundance of 36 functions (white) and 22 microbial families (blue) in the native rhizosphere compared to the effects of competition (3 functions, 16 families) or drought alone on natives (not shown: 5 functions, 0 families). (c) Additionally, regardless of watering treatment, invasive grasses sourced more of the taxonomic community in native-invasive mixes and this was exacerbated during drought. Overall, these results suggest invasion-driven shifts in the microbiome may be involved in weakening natives’ ability to cope with climate change, especially drought.
Optimal control theory techniques for nitrogen vacancy ensembles in single crystal diamond
Authors: Liddy Madelaine S. Z. , Borneman Troy , Sprenger Peter , Cory David
Published: September 2023

Nitrogen vacancy centre ensembles are excellent candidates for quantum sensors due to their vector magnetometry capabilities, deployability at room temperature and simple optical initialization and readout. This work describes the engineering and characterization methods required to control all four principle axis systems (P.A.S.) of NV ensembles in a single crystal diamond without an applied static magnetic field. Circularly polarized microwaves enable arbitrary simultaneous control with spin-locking experiments and collective control using optimal control theory (OCT) in a (100) diamond. These techniques may be further improved and integrated to realize high-sensitivity NV-based quantum sensing devices using all four P.A.S. systems.
Using an $$A^*$$-based framework for decomposing combinatorial optimization problems to employ NISQ computers
Authors: Garhofer Simon , Bringmann Oliver
Published: September 2023

Combinatorial optimization problems such as the traveling salesperson problem are ubiquitous in practical applications and notoriously difficult to solve optimally. Hence, many current endeavors focus on producing approximate solutions. The use of quantum computers could accelerate the generation of those approximate solutions or yield more exact approximations in comparable time. However, quantum computers are presently very limited in size and fidelity. In this work, we aim to address the issue of limited problem size by developing a scheme that decomposes a combinatorial optimization problem instance into arbitrarily small subinstances that can be solved on a quantum machine. This process utilizes A* as a foundation. Additionally, we present heuristics that reduce the runtime of the algorithm effectively, albeit at the cost of optimality. In experiments, we find that the heavy dependence of our approach on the choice of the heuristics used allows for a modifiable framework that can be adapted case by case instead of a concrete procedure.
Grounds for Exemption from Criminal Liability? How Forensic Linguistics Can Contribute to Terrorism Trials
Authors: Giménez García Roser , Queralt Sheila
Published: September 2023

Drawing on Brown and Fraser’s (in: Giles, Scherer (eds) Social markers in speech, Cambridge University Press, Cambridge, pp 33–62, 1979) framework for the analysis of communicative situations and Fuentes Rodríguez’s (Lingüística pragmática y Análisis del discurso, Arco Libros, Madrid, 2000; in Estudios de Lingüística: Investigaciones lingüísticas en el siglo XXI, 2009. https://doi.org/10.14198/ELUA2009.Anexo3.04) model of pragmatic analysis, this paper examines three home-made recordings featuring some of the members of the terrorist cell responsible for the 2017 vehicle-ramming attacks in Barcelona and Cambrils weighted as evidence during the trial held between November 2020 and May 2021 in the Spanish National High Court. The aim of this qualitative analysis is to test whether the linguistic evidence available supports the allegation that the participation in these recordings by one of the accused, Mohamed Houli Chemlal, had been planned by his interlocutors. Results show, first, that the exchanges analyzed present features indicative of both spontaneity and (limited) planification. Second, that Houli makes key contributions to the unfolding of the interactions shown in the recordings and that he does so in a cooperative and apparently relaxed manner, which could at best provide only partial support to his allegations. It is claimed that forensic linguistic analysis can generate valuable insights within terrorism-related legal proceedings.
Poverty as a Driver of Stigma among Finnish Children during the Covid-19 Pandemic– Evidence from the 2021 Children’s Voice Survey
Authors: Vuorenlinna Emily , Välimäki Sanni , Lindberg Marja , Sarkia Aino , Hakovirta Mia , Nygård Mikael
Published: September 2023

Stigma is a social problem that can have severe outcomes on both individuals and society. Previous research shows that children’s experiences of stigma may increase during times of stress and hardship such as the Covid-19 pandemic, but also that poverty and a lack of resources can create stigmatization. However, both stigma and poverty are multidimensional phenomena that have been investigated mainly among adults using single indicators. This article contributes to literature by studying children’s experiences of stigma and its relation to poverty by using a multidimensional approach. More specifically, it investigates Finnish children’s experienced and internalized stigma during the second year of the Covid-19 pandemic, and analyses how these dimensions are associated with subjective poverty and material deprivation. We use data from the 2021 Children’s Voice survey conducted by Save the Children, Finland. The results show that both dimensions of stigma are correlated with subjective poverty as well as material deprivation, even when controlling for socio-economic and other variables. Also low psychological wellbeing is a significant driver of both forms of stigma, while living in a one-parent household was significantly associated with internalized stigma, but not experienced stigma. By contrast, while higher self-esteem seem to reduce both forms of stigma, a higher number of good friends was found to only reduce experienced stigma. As there are both short- and long-term negative outcomes of stigma, for example in terms of mental health problems and social exclusion, child poverty should be taken seriously – especially during times of crises such as pandemics.
Relationship Between Short-chain Fatty Acids and Parkinson’s Disease: A Review from Pathology to Clinic
Authors: Duan Wen-Xiang , Wang Fen , Liu Jun-Yi , Liu Chun-Feng
Published: September 2023

Parkinson’s disease (PD) is a complicated neurodegenerative disease, characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies and neurites, and massive loss of midbrain dopamine neurons. Increasing evidence suggests that gut microbiota and microbial metabolites are involved in the development of PD. Among these, short-chain fatty acids (SCFAs), the most abundant microbial metabolites, have been proven to play a key role in brain-gut communication. In this review, we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor symptoms. Future research should focus on further elucidating the role of SCFAs in neuroinflammation, as well as developing novel strategies employing SCFAs and their derivatives to treat PD.
The Effect of Hormonal Contraceptive Use on Skeletal Muscle Hypertrophy, Power and Strength Adaptations to Resistance Exercise Training: A Systematic Review and Multilevel Meta-analysis
Authors: Nolan David , McNulty Kelly L. , Manninen Mika , Egan Brendan
Published: September 2023

Background

Resistance exercise training is widely used by general and athletic populations to increase skeletal muscle hypertrophy, power and strength. Endogenous sex hormones influence various bodily functions, including possibly exercise performance, and may influence adaptive changes in response to exercise training. Hormonal contraceptive (HC) use modulates the profile of endogenous sex hormones, and therefore, there is increasing interest in the impact, if any, of HC use on adaptive responses to resistance exercise training.

Objective

Our aim is to provide a quantitative synthesis of the effect of HC use on skeletal muscle hypertrophy, power and strength adaptations in response to resistance exercise training.

Methods

A systematic review with meta-analysis was conducted on experimental studies which directly compared skeletal muscle hypertrophy, power and strength adaptations following resistance exercise training in hormonal contraceptive users and non-users conducted before July 2023. The search using the online databases PUBMED, SPORTDiscus, Web of Science, Embase and other supplementary search strategies yielded 4669 articles, with 8 articles (54 effects and 325 participants) meeting the inclusion criteria. The methodological quality of the included studies was assessed using the “Tool for the assessment of study quality and reporting in exercise”.

Results

All included studies investigated the influence of oral contraceptive pills (OCP), with no study including participants using other forms of HC. The articles were analysed using a meta-analytic multilevel maximum likelihood estimator model. The results indicate that OCP use does not have a significant effect on hypertrophy [0.01, 95% confidence interval (CI) [− 0.11, 0.13], t = 0.14, p = 0.90), power (− 0.04, 95% CI [− 0.93, 0.84], t =  − 0.29, p = 0.80) or strength (0.10, 95% CI [− 0.08, 0.28], t = 1.48, p = 0.20).

Discussion

Based on the present analysis, there is no evidence-based rationale to advocate for or against the use of OCPs in females partaking in resistance exercise training to increase hypertrophy, power and/or strength. Rather, an individualised approach considering an individual’s response to OCPs, their reasons for use and menstrual cycle history may be more appropriate.

Registration

The review protocol was registered on PROSPERO (ID number and hyperlink: CRD42022365677).
Experiences of Inclusive School Settings for Children and Young People on the Autism Spectrum in the UK: a Systematic Review
Authors: El-Salahi Shama , Khaki Zahra , Vohora Reena
Published: September 2023

Increasing numbers of Children and Young People on the Autism Spectrum (CYP-AS) are attending inclusive education settings in the UK, yet research about the impact on their psychosocial well-being is scarce. This qualitative review examined the experiences of CYP-AS in British inclusive education settings. Systematic data retrieval on nine electronic databases identified 22 papers reporting 19 studies that were eligible for inclusion. A combination of narrative synthesis and critical review described and synthesised studies’ findings and assessed the risk of bias. The findings reinforce the idea that integration into mainstream schools alone is insufficient to support the psychosocial well-being of CYP-AS. Social connectedness and a sense of belonging may be critical factors that improve school experiences for this population.
Experimental investigation on slip conditions during thread rolling with flat dies
Authors: Volz Stefan , Groche Peter
Published: September 2023

The process design of flat die rolling operations can be a tedious and costly process due to the challenges posed by small process windows. Within this work, an effort is made to closely investigate and understand the process limits caused by excessive slippage of the workpiece. Optical measurements are carried out to capture the characteristics of excessive slippage and the influence of the stroke rate and the tribological system on this process limit. Large differences in slippage were observed, depending on the tribological system. While systems with polymer based lubricants showed excessive slippage at low stroke rates, systems using oil or no lubricant endured higher stroke rates before process limits were reached. The optical measurements revealed three major forms of slippage: successful rolling without slippage, failure due to excessive slippage at process start, and failure due to excessive slippage at around one workpiece rotation.
What hinge epistemology and Bayesian epistemology can learn from each other
Authors: Vassend Olav Benjamin
Published: September 2023

Hinge epistemology and Bayesianism are two prominent approaches in contemporary epistemology, but the relationship between these approaches has not been systematically studied. This paper formalizes the central commitments of hinge epistemology in a Bayesian framework and argues for the following two theses: (1) many of the types of claims that are treated as paradigmatic hinges in the hinge epistemology literature, such as the claim that there exists an external world of physical objects, are not capable of enabling rational inquiry, even though this is typically regarded as a central property of hinges; (2) the standard Bayesian story of how rational inquiry proceeds is incorrect or at best incomplete.
Topologically enhanced nonlinear optical response of graphene nanoribbon heterojunctions
Authors: Deng Hanying , Qu Zhihao , He Yingji , Huang Changming , Panoiu Nicolae C. , Ye Fangwei
Published: September 2023

We study the nonlinear optical properties of heterojunctions made of graphene nanoribbons (GNRs) consisting of two segments with either the same or different topological properties. By utilizing a quantum mechanical approach that incorporates distant-neighbor interactions, we demonstrate that the presence of topological interface states significantly enhances the second- and third-order nonlinear optical response of GNR heterojunctions that are created by merging two topologically inequivalent GNRs. Specifically, GNR heterojunctions with topological interface states display third-order harmonic hyperpolarizabilities that are more than two orders of magnitude larger than those of their similarly sized counterparts without topological interface states, whereas the second-order harmonic hyperpolarizabilities exhibit a more than ten-fold contrast between heterojunctions with and without topological interface states. Additionally, we find that the topological state at the interface between two topologically distinct GNRs can induce a noticeable red-shift of the quantum plasmon frequency of the heterojunctions. Our results reveal a general and profound connection between the existence of topological states and an enhanced nonlinear optical response of graphene nanostructures and possible other photonic systems.
Education for All?
Authors: Martin Cathie Jo
Published: September 2023

Why did Denmark develop mass education for all in 1814, while Britain created a public-school system only in 1870 that primarily educated academic achievers? Cathie Jo Martin argues that fiction writers and their literary narratives inspired education campaigns throughout the nineteenth-century. Danish writers imagined mass schools as the foundation for a great society and economic growth. Their depictions fortified the mandate to educate all people and showed neglecting low-skill youth would waste societal resources and threaten the social fabric. Conversely, British authors pictured mass education as harming social stability, lower-class work, and national culture. Their stories of youths who overcame structural injustices with individual determination made it easier to blame students who failed to seize educational opportunities. Novel and compelling, Education for All? uses a multidisciplinary perspective to offer a unique gaze into historical policymaking. This title is part of the Flip it Open Programme and may also be available Open Access. Check our website Cambridge Core for details.
A failed but useful constitution-making process: How Bachelet’s process contributed to constitution-making in Chile
Authors: García José Francisco
Published: September 2023

This article shows how failed constitutional proposals may contribute to future constitution-making processes by exploring the relationship between the recently failed Chilean constitution-making process (2019–22) and the previous unsuccessful one led by former President Michelle Bachelet (2015–17). Comparative constitutional scholars are yet to fully understand how constitutional failures of this kind can take place, and Bachelet’s process has not received the attention it should. This article fills that gap by showing how both processes were driven by shared principles initially set by Bachelet. It also shows how those principles may serve as a blueprint for future constitutional changes in Chile. Bachelet had campaigned on the basis that any constitutional replacement attempt should beparticipatory, institutionalanddemocratic– all ideas that have remained popular in Chile’s political landscape. Those ideas have served the purpose of both reducing transaction costs among constitutional negotiators and securing large compromises in polarized political scenarios.
Cryovolcanism’s Song of Ice and Fire
Authors: Klemetti Erik
Published: September 2023

Ocean moons of the outer solar system hint at ice volcanoes, hydrothermal vents, and the tantalizing chance of habitability.
Micromechanical Contrast of Ordos Basin Sandstone‐Mudstone Interbedded Layered Rocks
Authors: Yang Ruiyue , Cong Richao , Gong Yanjin , Pang Zhaoyu , Huang Zhongwei , Li Gensheng
Published: September 2023

Layered rocks are heterogeneous media composed of multiscale minerals with contrasting geomechanical properties. It remains unclear how the mechanical responses of constituent minerals among different adjacent layers vary in a microscale. Based on the grid nanoindentation tests assisted by high‐resolution scanning electron microscopy and energy‐dispersive spectroscopy techniques, we quantified the mechanical responses of various minerals in an interbedded sandstone‐mudstone core sample and provided visual mineralogies and indentation patterns of different adjacent layers. Results show that the Young's modulus, hardness, and elasticity index of quartz and dolomite decrease, whereas their fracture toughness and plastic work ratio increase from the sandstone layer to the mudstone layer. Quartz displays elastic‐dominated deformations in the sandstone layer whereas transforms into medium‐plastic deformations in the mudstone layer. The mean values of Young's modulus, hardness, and elasticity index of quartz in the sandstone layer are 1.28, 2.00, and 1.56 times higher than that in the mudstone layer, respectively. Dolomite and phyllosilicate minerals show prominently plastic‐dominated deformations in each layer. When an indenter encounters multiple minerals simultaneously, the mechanical responses are determined by the softer phases and irregular indent impressions are generated. Shear and radical cracks are prone to occur in the elastic‐dominated minerals, while chipping damage is induced in the plastic‐dominated minerals. This work provides new insights and fundamental understandings in geomechanical properties contrasts in multilayered rocks, and can facilitate the geomechanical modeling and upscaling schemes in multilayered formations.
SE‐Dome II Ice Core Dating With Half‐Year Precision: Increasing Melting Events From 1799 to 2020 in Southeastern Greenland
Authors: Kawakami Kaoru , Iizuka Yoshinori , Sasage Mahiro , Matsumoto Mai , Saito Takeshi , Hori Akira , Ishino Sakiko , Fujita Shuji , Fujita Koji , Takasugi Keita , Hatakeyama Takumi , Hamamoto Saaya , Watari Akihisa , Esashi Nao , Otsuka Miu , Uemura Ryu , Horiuchi Kazuho , Minowa Masahiro , Hattori Shohei , Aoki Teruo , Hirabayashi Motohiro , Kawamura Kenji , Matoba Sumito
Published: September 2023

Arctic warming has accelerated surface melting even in the highland areas of the Greenland ice sheet (GrIS). Understanding the relationship between climate and surface melting is essential for improving the estimates of ice‐sheet mass loss due to warming. Here we analyze a 250 m‐long ice core from the southeastern dome of GrIS (SE‐Dome site; 67°19′17″ N, 36°47′03″ W, 3,161 m a.s.l.), where the annual mean temperature is −20.9°C and the accumulation rate is high and there is a large discrepancy among climate models regarding snow accumulation estimates. A time scale was established for 1799–2020 with a half‐year uncertainty using annual counting of H2O2 concentration and five time horizons determined by electrical conductivity, melt events, and tritium concentration. The annual accumulation rate from the ice core shows no significant trend over 221 years and has an average of 1.04 ± 0.20 m w.e. year−1. In contrast, the frequency and thickness of refrozen melt layer (ML) have increased over 221 years, and are synchronized with temperature changes in the Arctic. The thickness of MLs correlates positively with the time‐integrated summer temperature anomaly using a reanalysis of air temperature. The in‐situ accumulation records in the southeastern GrIS provide an important basis for correcting reanalysis data such as ERA5, which in turn are valuable for improving regional climate models.
Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study
Authors: Sun Juxian , Mao Feifei , Liu Chang , Zhang Fan , Jiang Dafeng , Guo Weixing , Huo Lei , Zhou Liping , Lau Wan Yee , Shi Jie , Cheng Shuqun
Published: September 2023

The majority of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage. Currently, there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis (EHM). Systemic chemotherapy, such as FOLFOX4 (infusions of fluorouracil, leucovorin, and oxaliplatin), has been reported for treating advanced HCC with EHM, but its effectiveness is very poor. In this randomized, double-blind, placebo-controlled study, we aimed to assess the efficacy and safety of FOLFOX4 with all-trans-retinoic acid (ATRA) as a palliative treatment for HCC patients with EHM, compared to FOLFOX4 with a placebo. The primary endpoint was overall survival (OS), and subsequently, an exploratory model was developed based on bioinformatics to predict the efficacy of FOLFOX4-ATRA treatment. A total of 108 patients were randomly assigned in a 1:1 ratio to receive either FOLFOX4-ATRA or FOLFOX4-placebo. The intention-to-treat (ITT) population showed a median OS of 16.2 months for the FOLFOX4-ATRA group, compared with 10.7 months for the FOLFOX4-placebo group (HR 0.56, 95% CI 0.33–0.93; p = 0.025). The median progression-free survival (PFS) was 7.1 months for the FOLFOX4-ATRA group and 4.2 months for the FOLFOX4-placebo group (HR 0.62, 95% CI 0.41–0.94; p = 0.024). A panel of proteins with unique upregulation during complete response (CR) (SOD3, TTR, SSC5D, GP5, IGKV1D-33) and partial response (PR) (TGFB1, GSS, IGHV5-10-1) effectively predicted CR and PR in patients treated with FOLFOX4-ATRA, as compared to FOLFOX4-placebo. The results suggest that FOLFOX4-ATRA is a safe and effective treatment for patients with advanced HCC and EHM in eastern China.
Development and validation of a multivariable model for prediction of malignant transformation and recurrence of oral epithelial dysplasia
Authors: Mahmood Hanya , Shephard Adam , Hankinson Paul , Bradburn Mike , Araujo Anna Luiza Damaceno , Santos-Silva Alan Roger , Lopes Marcio Ajudarte , Vargas Pablo Agustin , McCombe Kris D. , Craig Stephanie G. , James Jacqueline , Brooks Jill , Nankivell Paul , Mehanna Hisham , Rajpoot Nasir , Khurram Syed Ali
Published: September 2023

Background

Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes.

Methods

A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months.

Results

Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model.

Conclusions

This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication.
Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer
Authors: Lambrechts Yentl , Garg Abhishek D. , Floris Giuseppe , Punie Kevin , Neven Patrick , Nevelsteen Ines , Govaerts Jannes , Richard François , Laenen Annouschka , Desmedt Christine , Wildiers Hans , Hatse Sigrid
Published: September 2023

There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof of concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.
Resonant X-ray excitation of the nuclear clock isomer 45Sc
Authors: Shvyd’ko Yuri , Röhlsberger Ralf , Kocharovskaya Olga , Evers Jörg , Geloni Gianluca Aldo , Liu Peifan , Shu Deming , Miceli Antonino , Stone Brandon , Hippler Willi , Marx-Glowna Berit , Uschmann Ingo , Loetzsch Robert , Leupold Olaf , Wille Hans-Christian , Sergeev Ilya , Gerharz Miriam , Zhang Xiwen , Grech Christian , Guetg Marc , Kocharyan Vitali , Kujala Naresh , Liu Shan , Qin Weilun , Zozulya Alexey , Hallmann Jörg , Boesenberg Ulrike , Jo Wonhyuk , Möller Johannes , Rodriguez-Fernandez Angel , Youssef Mohamed , Madsen Anders , Kolodziej Tomasz
Published: September 2023

Resonant oscillators with stable frequencies and large quality factors help us to keep track of time with high precision. Examples range from quartz crystal oscillators in wristwatches to atomic oscillators in atomic clocks, which are, at present, our most precise time measurement devices1. The search for more stable and convenient reference oscillators is continuing2–6. Nuclear oscillators are better than atomic oscillators because of their naturally higher quality factors and higher resilience against external perturbations7–9. One of the most promising cases is an ultra-narrow nuclear resonance transition in 45Sc between the ground state and the 12.4-keV isomeric state with a long lifetime of 0.47 s (ref. 10). The scientific potential of 45Sc was realized long ago, but applications require 45Sc resonant excitation, which in turn requires accelerator-driven, high-brightness X-ray sources11 that have become available only recently. Here we report on resonant X-ray excitation of the 45Sc isomeric state by irradiation of Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser and subsequent detection of nuclear decay products. Simultaneously, the transition energy was determined as $${\mathrm{12,389.59}}_{+0.12\left({\rm{syst}}\right)}^{\pm 0.15\left({\rm{stat}}\right)}\,{\rm{eV}}$$

12,389.59

+
0.12

syst

±
0.15

stat

eV

with an uncertainty that is two orders of magnitude smaller than the previously known values. These advancements enable the application of this isomer in extreme metrology, nuclear clock technology, ultra-high-precision spectroscopy and similar applications.
The geography of climate and the global patterns of species diversity
Authors: Coelho Marco Túlio P. , Barreto Elisa , Rangel Thiago F. , Diniz-Filho José Alexandre F. , Wüest Rafael O. , Bach Wilhelmine , Skeels Alexander , McFadden Ian R. , Roberts David W. , Pellissier Loïc , Zimmermann Niklaus E. , Graham Catherine H.
Published: September 2023

Climate’s effect on global biodiversity is typically viewed through the lens of temperature, humidity and resulting ecosystem productivity1–6. However, it is not known whether biodiversity depends solely on these climate conditions, or whether the size and fragmentation of these climates are also crucial. Here we shift the common perspective in global biodiversity studies, transitioning from geographic space to a climate-defined multidimensional space. Our findings suggest that larger and more isolated climate conditions tend to harbour higher diversity and species turnover among terrestrial tetrapods, encompassing more than 30,000 species. By considering both the characteristics of climate itself and its geographic attributes, we can explain almost 90% of the variation in global species richness. Half of the explanatory power (45%) may be attributed either to climate itself or to the geography of climate, suggesting a nuanced interplay between them. Our work evolves the conventional idea that larger climate regions, such as the tropics, host more species primarily because of their size7,8. Instead, we underscore the integral roles of both the geographic extent and degree of isolation of climates. This refined understanding presents a more intricate picture of biodiversity distribution, which can guide our approach to biodiversity conservation in an ever-changing world.
Inactivation of the Kv2.1 channel through electromechanical coupling
Authors: Fernández-Mariño Ana I. , Tan Xiao-Feng , Bae Chanhyung , Huffer Kate , Jiang Jiansen , Swartz Kenton J.
Published: September 2023

The Kv2.1 voltage-activated potassium (Kv) channel is a prominent delayed-rectifier Kv channel in the mammalian central nervous system, where its mechanisms of activation and inactivation are critical for regulating intrinsic neuronal excitability1,2. Here we present structures of the Kv2.1 channel in a lipid environment using cryo-electron microscopy to provide a framework for exploring its functional mechanisms and how mutations causing epileptic encephalopathies3–7 alter channel activity. By studying a series of disease-causing mutations, we identified one that illuminates a hydrophobic coupling nexus near the internal end of the pore that is critical for inactivation. Both functional and structural studies reveal that inactivation in Kv2.1 results from dynamic alterations in electromechanical coupling to reposition pore-lining S6 helices and close the internal pore. Consideration of these findings along with available structures for other Kv channels, as well as voltage-activated sodium and calcium channels, suggests that related mechanisms of inactivation are conserved in voltage-activated cation channels and likely to be engaged by widely used therapeutics to achieve state-dependent regulation of channel activity.
piRNA processing by a trimeric Schlafen-domain nuclease
Authors: Podvalnaya Nadezda , Bronkhorst Alfred W. , Lichtenberger Raffael , Hellmann Svenja , Nischwitz Emily , Falk Torben , Karaulanov Emil , Butter Falk , Falk Sebastian , Ketting René F.
Published: September 2023

Transposable elements are genomic parasites that expand within and spread between genomes1. PIWI proteins control transposon activity, notably in the germline2,3. These proteins recognize their targets through small RNA co-factors named PIWI-interacting RNAs (piRNAs), making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. Although the processing of piRNA precursors is an essential step in this process, many of the molecular details remain unclear. Here, we identify an endoribonuclease, precursor of 21U RNA 5′-end cleavage holoenzyme (PUCH), that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain proteins (SLFL proteins), executes 5′-end piRNA precursor cleavage. PUCH-mediated processing strictly requires a 7-methyl-G cap (m7G-cap) and a uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds to piRNA precursors4, and that this interaction enhances piRNA production in vivo. The identification of PUCH concludes the search for the 5′-end piRNA biogenesis factor in C. elegans and uncovers a type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (SLFN) genes have been associated with immunity5, exposing a molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.
Proteome census upon nutrient stress reveals Golgiphagy membrane receptors
Authors: Hickey Kelsey L. , Swarup Sharan , Smith Ian R. , Paoli Julia C. , Miguel Whelan Enya , Paulo Joao A. , Harper J. Wade
Published: September 2023

During nutrient stress, macroautophagy degrades cellular macromolecules, thereby providing biosynthetic building blocks while simultaneously remodelling the proteome1,2. Although the machinery responsible for initiation of macroautophagy has been well characterized3,4, our understanding of the extent to which individual proteins, protein complexes and organelles are selected for autophagic degradation, and the underlying targeting mechanisms, is limited. Here we use orthogonal proteomic strategies to provide a spatial proteome census of autophagic cargo during nutrient stress in mammalian cells. We find that macroautophagy has selectivity for recycling membrane-bound organelles (principally Golgi and endoplasmic reticulum). Through autophagic cargo prioritization, we identify a complex of membrane-embedded proteins, YIPF3 and YIPF4, as receptors for Golgiphagy. During nutrient stress, YIPF3 and YIPF4 interact with ATG8 proteins through LIR motifs and are mobilized into autophagosomes that traffic to lysosomes in a process that requires the canonical autophagic machinery. Cells lacking YIPF3 or YIPF4 are selectively defective in elimination of a specific cohort of Golgi membrane proteins during nutrient stress. Moreover, YIPF3 and YIPF4 play an analogous role in Golgi remodelling during programmed conversion of stem cells to the neuronal lineage in vitro. Collectively, the findings of this study reveal prioritization of membrane protein cargo during nutrient-stress-dependent proteome remodelling and identify a Golgi remodelling pathway that requires membrane-embedded receptors.
Disulfidptosis-associated lncRNAs predict breast cancer subtypes
Authors: Xia Qing , Yan Qibin , Wang Zehua , Huang Qinyuan , Zheng Xinying , Shen Jinze , Du Lihua , Li Hanbing , Duan Shiwei
Published: September 2023

Disulfidptosis is a newly discovered mode of cell death. However, its relationship with breast cancer subtypes remains unclear. In this study, we aimed to construct a disulfidptosis-associated breast cancer subtype prediction model. We obtained 19 disulfidptosis-related genes from published articles and performed correlation analysis with lncRNAs differentially expressed in breast cancer. We then used the random forest algorithm to select important lncRNAs and establish a breast cancer subtype prediction model. We identified 132 lncRNAs significantly associated with disulfidptosis (FDR < 0.01, |R|> 0.15) and selected the first four important lncRNAs to build a prediction model (training set AUC = 0.992). The model accurately predicted breast cancer subtypes (test set AUC = 0.842). Among the key lncRNAs, LINC02188 had the highest expression in the Basal subtype, while LINC01488 and GATA3-AS1 had the lowest expression in Basal. In the Her2 subtype, LINC00511 had the highest expression level compared to other key lncRNAs. GATA3-AS1 had the highest expression in LumA and LumB subtypes, while LINC00511 had the lowest expression in these subtypes. In the Normal subtype, GATA3-AS1 had the highest expression level compared to other key lncRNAs. Our study also found that key lncRNAs were closely related to RNA methylation modification and angiogenesis (FDR < 0.05, |R|> 0.1), as well as immune infiltrating cells (P.adj < 0.01, |R|> 0.1). Our random forest model based on disulfidptosis-related lncRNAs can accurately predict breast cancer subtypes and provide a new direction for research on clinical therapeutic targets for breast cancer.
The influence mechanism of industrial policies on Chinese companies' cross-border M&A decision-making
Authors: Shen Yalan , Yang Mengqi , An Hongyu , Li Kailun
Published: September 2023

This study explored the potential links between Chinese industrial policy and cross-border mergers and acquisitions by Chinese firms from 2009 to 2019. Based on describing China's industrial strategy and evaluating the then-current situation of Chinese enterprises' cross-border mergers and acquisitions, this empirical study constructed a two-way fixed-effect panel model and an intermediate effect model to assess the mechanism of industrial policy's influence on Chinese enterprises' cross-border mergers and acquisitions decisions. The findings were as follows: (1) Industrial policy could promote the implementation of cross-border mergers and acquisitions of Chinese enterprises; (2) By easing financial restrictions, industrial policy could improve firms' access to capital and encourage cross-border mergers and acquisitions. (3) Industrial policies could promote the high political relevance of state-owned enterprises, thus promoting the success of transnational mergers and acquisitions of enterprises. Therefore, it was significant to promote the transformation of industrial policy from subsidy-oriented to performance-oriented and rationally evaluate the risks and benefits of M&A for enterprises to complete cross-border M&A.
Semi-natural housing rescues social behavior and reduces repetitive exploratory behavior of BTBR autistic-like mice
Authors: Binder Matthew S. , Bordey Angelique
Published: September 2023

Environmental enrichment confers numerous benefits when implemented in murine models and can reduce behavioral symptomatology in models of disease, such as autism spectrum disorder (ASD). However, previous work did not examine the impact of early-life environmental enrichment on each core feature of ASD. We thus implemented a social and physical enrichment at birth, modeling a semi-natural housing, and examined its impact on communicative, social, sensory, and repetitive behaviors using BTBR (autistic-like) and C57BL/6 J (B6, wildtype) mice, comparing them to standard housing conditions. We found that environmental enrichment alleviated the social deficit of juvenile BTBR mice and reduced their repetitive exploratory behavior but did not affect their rough versus smooth texture preference nor the number of maternal isolation-induced pup calls. Environmental enrichment only affected the call characteristics of B6 mice. One interpretation of these data is that early-life environmental enrichment has significant therapeutic potential to treat selective core features of ASD. Another interpretation is that reducing environmental complexity causes selective behavioral deficits in ASD-prone mice suggesting that current standard housing may be suboptimal. Overall, our data illustrate the extent to which the environment influences behavior and highlights the importance of considering housing conditions when designing experiments and interpreting behavioral results.
Improving air quality assessment using physics-inspired deep graph learning
Authors: Li Lianfa , Wang Jinfeng , Franklin Meredith , Yin Qian , Wu Jiajie , Camps-Valls Gustau , Zhu Zhiping , Wang Chengyi , Ge Yong , Reichstein Markus
Published: September 2023

Existing methods for fine-scale air quality assessment have significant gaps in their reliability. Purely data-driven methods lack any physically-based mechanisms to simulate the interactive process of air pollution, potentially leading to physically inconsistent or implausible results. Here, we report a hybrid multilevel graph neural network that encodes fluid physics to capture spatial and temporal dynamic characteristics of air pollutants. On a multi-air pollutant test in China, our method consistently improved extrapolation accuracy by an average of 11–22% compared to several baseline machine learning methods, and generated physically consistent spatiotemporal trends of air pollutants at fine spatial and temporal scales.
Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by reducing signaling activity through epitope selection
Authors: Akiba Hiroki , Fujita Junso , Ise Tomoko , Nishiyama Kentaro , Miyata Tomoko , Kato Takayuki , Namba Keiichi , Ohno Hiroaki , Kamada Haruhiko , Nagata Satoshi , Tsumoto Kouhei
Published: September 2023

Conventional bivalent antibodies against cell surface receptors often initiate unwanted signal transduction by crosslinking two antigen molecules. Biparatopic antibodies (BpAbs) bind to two different epitopes on the same antigen, thus altering crosslinking ability. In this study, we develop BpAbs against tumor necrosis factor receptor 2 (TNFR2), which is an attractive immune checkpoint target. Using different pairs of antibody variable regions specific to topographically distinct TNFR2 epitopes, we successfully regulate the size of BpAb–TNFR2 immunocomplexes to result in controlled agonistic activities. Our series of results indicate that the relative positions of the two epitopes recognized by the BpAb are critical for controlling its signaling activity. One particular antagonist, Bp109-92, binds TNFR2 in a 1:1 manner without unwanted signal transduction, and its structural basis is determined using cryo-electron microscopy. This antagonist suppresses the proliferation of regulatory T cells expressing TNFR2. Therefore, the BpAb format would be useful in designing specific and distinct antibody functions.
Methamphetamine-induced region-specific transcriptomic and epigenetic changes in the brain of male rats
Authors: Miao Benpeng , Xing Xiaoyun , Bazylianska Viktoriia , Madden Pamela , Moszczynska Anna , Zhang Bo
Published: September 2023

Psychostimulant methamphetamine (METH) is neurotoxic to the brain and, therefore, its misuse leads to neurological and psychiatric disorders. The gene regulatory network (GRN) response to neurotoxic METH binge remains unclear in most brain regions. Here we examined the effects of binge METH on the GRN in the nucleus accumbens, dentate gyrus, Ammon’s horn, and subventricular zone in male rats. At 24 h after METH, ~16% of genes displayed altered expression and over a quarter of previously open chromatin regions - parts of the genome where genes are typically active - showed shifts in their accessibility. Intriguingly, most changes were unique to each area studied, and independent regulation between transcriptome and chromatin accessibility was observed. Unexpectedly, METH differentially impacted gene activity and chromatin accessibility within the dentate gyrus and Ammon’s horn. Around 70% of the affected chromatin-accessible regions in the rat brain have conserved DNA sequences in the human genome. These regions frequently act as enhancers, ramping up the activity of nearby genes, and contain mutations linked to various neurological conditions. By sketching out the gene regulatory networks associated with binge METH in specific brain regions, our study offers fresh insights into how METH can trigger profound, region-specific molecular shifts.