bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Application of the Branched and Isoprenoid GDGT Machine Learning Classification Algorithm (BIGMaC) for Paleoenvironmental Reconstruction
Authors: Martínez‐Sosa Pablo , Tierney Jessica E. , Pérez‐Angel Lina C. , Stefanescu Ioana C. , Guo Jingjing , Kirkels Frédérique , Sepúlveda Julio , Peterse Francien , Shuman Bryan N. , Reyes Alberto V.
Published: July 2023

Glycerol dialkyl glycerol tetraethers (GDGTs), both archaeal isoprenoid GDGTs (isoGDGTs) and bacterial branched GDGTs (brGDGTs), have been used in paleoclimate studies to reconstruct environmental conditions. Since GDGTs are produced in many types of environments, their relative abundances also depend on the depositional setting. This suggests that the distribution of GDGTs also preserves useful information that can be used more broadly to infer these depositional environments in the geological past. Here, we combined existing iso‐ and brGDGT relative abundance data with newly analyzed samples to generate a database of 1,153 samples from several modern sedimentary settings. We observed a robust relationship between the depositional environment and the relative abundances of GDGTs in our samples. This data set was used to train and test the Branched and isoGDGT Machine learning Classification (BIGMaC) algorithm, which identifies the environment a sample comes from based on the distribution of GDGTs with high precision and recall (F1 = 0.95). We tested the model on the sedimentary record from the Giraffe kimberlite pipe, an Eocene maar in subantarctic Canada, and found that the BIGMaC reconstruction agrees with independent stratigraphic and palynological information, provides new information about the paleoenvironment of this site, and helps improve its paleotemperature reconstruction. In contrast, we also include an example from the PETM‐aged Cobham lignite as a cautionary example that illustrates the limitations of the algorithm. We propose that in cases where paleoenvironments are unknown or are changing, BIGMaC can be applied in concert with other proxies to generate more refined paleoclimate records.
Effect of eucalyptus oil on Streptococcus mutans and Enterococcus faecalis growth
Authors: Balhaddad Abdulrahman A. , AlSheikh Rasha N.
Published: July 2023

Objectives

There is a significant apprehension in medicine and dentistry concerning the emergence of antibiotic-resistant pathogens, as it composes a significant threat to global health, particularly oral health. The growing concern that oral pathogens may develop resistance against standard preventive measures raises the need for alternative measures to prevent these pathogens’ growth without inducing microbial resistance. Therefore, this study aims to assess the antibacterial properties of eucalyptus oil (EO) against two main oral disease pathogens, Streptococcus mutans, and Enterococci faecalis.

Methods

S. mutans and E. faecalis biofilms were initiated using brain-heart infusion (BHI) broth supplemented with 2% sucrose with and without diluted EO. After 24 h of biofilm formation, total absorbance was measured via spectrophotometer; then, the biofilm was fixed, stained with crystal violet dye, and measured at 490 nm. An Independent t-test was used to compare the outcomes.

Results

Diluted EO revealed significant total absorbance reduction against S. mutans and E. faecalis compared to the control (p ≤ 0.001). For the biofilm measurement, S. mutans and E. faecalis biofilms were reduced by around 60- and 30-fold, respectively, compared to the group with no EO (p ≤ 0.001).

Conclusion

Based on this study’s results, using EO as an organic compound could be considered an adjunctive tool in preventing the growth of oral pathogens causing dental caries and endodontic infection.
USP11-mediated LSH deubiquitination inhibits ferroptosis in colorectal cancer through epigenetic activation of CYP24A1
Authors: Duan Junyi , Huang Daoyuan , Liu Cheng , Lv Yangbo , Zhang Lei , Chang Fen , Zeng Xiangyu , Li Li , Wang Weiping , Shao Genze
Published: July 2023

Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation. Colorectal cancer (CRC) cells evade ferroptosis despite their requirement of substantial iron and reactive oxygen species (ROS) to sustain active metabolism and extensive proliferation. However, the underlying mechanism is unclear. Herein, we report the role of lymphoid-specific helicase (LSH), a chromatin-remodeling protein, in suppressing erastin-induced ferroptosis in CRC cells. We demonstrate that erastin treatment leads to dose- and time-dependent downregulation of LSH in CRC cells, and depletion of LSH increases cell sensitivity to ferroptosis. Mechanistically, LSH interacts with and is stabilized by ubiquitin-specific protease 11 (USP11) via deubiquitination; this interaction was disrupted by erastin treatment, resulting in increased ubiquitination and LSH degradation. Moreover, we identified cytochrome P450 family 24 subfamily A member 1 (CYP24A1) as a transcriptional target of LSH. LSH binds to the CYP24A1 promoter, promoting nucleosome eviction and reducing H3K27me3 occupancy, thus leading to transcription of CYP24A1. This cascade inhibits excessive intracellular Ca2+ influx, thereby reducing lipid peroxidation and ultimately conferring resistance to ferroptosis. Importantly, aberrant expression of USP11, LSH, and CYP24A1 is observed in CRC tissues and correlates with poor patient prognosis. Taken together, our study demonstrates the crucial role of the USP11/LSH/CYP24A1 signaling axis in inhibiting ferroptosis in CRC, highlighting its potential as a therapeutic target in CRC treatment.
Holding water in a sieve—stable droplets without surface tension
Authors: Longmire N. P. , Showalter S. L. , Banuti D. T.
Published: July 2023

Our understanding of supercritical fluids has seen exciting advances over the last decades, often in direct contradiction to established textbook knowledge. Rather than being structureless, we now know that distinct supercritical liquid and gaseous states can be distinguished and that a higher order phase transition - pseudo boiling - occurs between supercritical liquid and gaseous states across the Widom line. Observed droplets and sharp interfaces at supercritical pressures are interpreted as evidence of surface tension due to phase equilibria in mixtures, given the lack of a supercritical liquid-vapor phase equilibrium in pure fluids. However, here we introduce an alternative physical mechanism that unexpectedly causes a sharpening of interfacial density gradients in absence of surface tension: thermal gradient induced interfaces (TGIIF). We show from first principles and simulations that, unlike in gases or liquids, stable droplets, bubbles, and planar interfaces can exist without surface tension. These results challenge and generalize our understanding of what droplets and phase interfaces are, and uncover yet another unexpected behavior of supercritical fluids. TGIIF provide a new physical mechanism that could be used to tailor and optimize fuel injection or heat transfer processes in high-pressure power systems.
Tesla valves and capillary structures-activated thermal regulator
Authors: Li Wenming , Yang Siyan , Chen Yongping , Li Chen , Wang Zuankai
Published: July 2023

Two-phase (liquid, vapor) flow in confined spaces is fundamentally interesting and practically important in many practical applications such as thermal management, offering the potential to impart high thermal transport performance owing to high surface-to-volume ratio and latent heat released during liquid/vapor phase transition. However, the associated physical size effect, in coupling with the striking contrast in specific volume between liquid and vapor phases, also leads to the onset of unwanted vapor backflow and chaotic two-phase flow patterns, which seriously deteriorates the practical thermal transport performances. Here, we develop a thermal regulator consisting of classical Tesla valves and engineered capillary structures, which can switch its working states and boost its heat transfer coefficient and critical heat flux in its “switched-on” state. We demonstrate that the Tesla valves and the capillary structures serve to eliminate vapor backflow and promote liquid flow along the sidewalls of both Tesla valves and main channels, respectively, which synergistically enable the thermal regulator to self-adapt to varying working conditions by rectifying the chaotic two-phase flow into an ordered and directional flow. We envision that revisiting century-old design can promote the development of next generation cooling devices towards switchable and very high heat transfer performances for power electronic devices.
A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2
Authors: Losa Marta , Barozzi Iros , Osterwalder Marco , Hermosilla-Aguayo Viviana , Morabito Angela , Chacón Brandon H. , Zarrineh Peyman , Girdziusaite Ausra , Benazet Jean Denis , Zhu Jianjian , Mackem Susan , Capellini Terence D. , Dickel Diane , Bobola Nicoletta , Zuniga Aimée , Visel Axel , Zeller Rolf , Selleri Licia
Published: July 2023

A lingering question in developmental biology has centered on how transcription factors with widespread distribution in vertebrate embryos can perform tissue-specific functions. Here, using the murine hindlimb as a model, we investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed primarily as HOX cofactors, attain context-specific developmental roles despite ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb phenotypes. By combining tissue-specific and temporally controlled mutagenesis with multi-omics approaches, we reconstruct a gene regulatory network (GRN) at organismal-level resolution that is collaboratively directed by PBX1/2 and HAND2 interactions in subsets of posterior hindlimb mesenchymal cells. Genome-wide profiling of PBX1 binding across multiple embryonic tissues further reveals that HAND2 interacts with subsets of PBX-bound regions to regulate limb-specific GRNs. Our research elucidates fundamental principles by which promiscuous transcription factors cooperate with cofactors that display domain-restricted localization to instruct tissue-specific developmental programs.
On-site growth of perovskite nanocrystal arrays for integrated nanodevices
Authors: Jastrzebska-Perfect Patricia , Zhu Weikun , Saravanapavanantham Mayuran , Li Zheng , Spector Sarah O. , Brenes Roberto , Satterthwaite Peter F. , Ram Rajeev J. , Niroui Farnaz
Published: July 2023

Despite remarkable progress in the development of halide perovskite materials and devices, their integration into nanoscale optoelectronics has been hindered by a lack of control over nanoscale patterning. Owing to their tendency to degrade rapidly, perovskites suffer from chemical incompatibility with conventional lithographic processes. Here, we present an alternative, bottom-up approach for precise and scalable formation of perovskite nanocrystal arrays with deterministic control over size, number, and position. In our approach, localized growth and positioning is guided using topographical templates of controlled surface wettability through which nanoscale forces are engineered to achieve sub-lithographic resolutions. With this technique, we demonstrate deterministic arrays of CsPbBr3nanocrystals with tunable dimensions down to <50 nm and positional accuracy <50 nm. Versatile, scalable, and compatible with device integration processes, we then use our technique to demonstrate arrays of nanoscale light-emitting diodes, highlighting the new opportunities that this platform offers for perovskites’ integration into on-chip nanodevices.
Detecting temporal and spatial malaria patterns from first antenatal care visits
Authors: Pujol Arnau , Brokhattingen Nanna , Matambisso Glória , Mbeve Henriques , Cisteró Pau , Escoda Anna , Maculuve Sónia , Cuna Boaventura , Melembe Cardoso , Ndimande Nelo , Munguambe Humberto , Montaña Júlia , Nhamússua Lídia , Simone Wilson , Tetteh Kevin K. A. , Drakeley Chris , Gamain Benoit , Chitnis Chetan E. , Chauhan Virander , Quintó Llorenç , Chidimatembue Arlindo , Martí-Soler Helena , Galatas Beatriz , Guinovart Caterina , Saúte Francisco , Aide Pedro , Macete Eusébio , Mayor Alfredo
Published: July 2023

Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. We assessed the spatio-temporal relationship between malaria trends at ANC (n = 6471) and in children in the community (n = 3933) and at health facilities (n = 15,467) in southern Mozambique (2016–2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC] > 0.8, χ²<1.1), with a 2–3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, did multigravidae show lower rates than children (PCC = 0.61, 95%CI[−0.12–0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC = 0.74, 95%CI[0.24–0.77]). 60% (9/15) of hotspots detected from health facility data (n = 6662) using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data (n = 3616). Taken together, we show that ANC-based malaria surveillance offers contemporary information on temporal trends and geographic distribution of malaria burden in the community.
Bias assessment of a test-negative design study of COVID-19 vaccine effectiveness used in national policymaking
Authors: Graham Sophie , Tessier Elise , Stowe Julia , Bernal Jamie Lopez , Parker Edward P. K. , Nitsch Dorothea , Miller Elizabeth , Andrews Nick , Walker Jemma L. , McDonald Helen I.
Published: July 2023

National test-negative-case-control (TNCC) studies are used to monitor COVID-19 vaccine effectiveness in the UK. A questionnaire was sent to participants from the first published TNCC COVID-19 vaccine effectiveness study conducted by the UK Health Security Agency, to assess for potential biases and changes in behaviour related to vaccination. The original study included symptomatic adults aged ≥70 years testing for COVID-19 between 08/12/2020 and 21/02/2021. A questionnaire was sent to cases and controls tested from 1–21 February 2021. In this study, 8648 individuals responded to the questionnaire (36.5% response). Using information from the questionnaire to produce a combined estimate that accounted for all potential biases decreased the original vaccine effectiveness estimate after two doses of BNT162b2 from 88% (95% CI: 79–94%) to 85% (95% CI: 68–94%). Self-reported behaviour demonstrated minimal evidence of riskier behaviour after vaccination. These findings offer reassurance to policy makers and clinicians making decisions based on COVID-19 vaccine effectiveness TNCC studies.
Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity
Authors: Zhong Dengqin , Wang Ruiyun , Zhang Hongjing , Wang Mengmeng , Zhang Xuxia , Chen Honghong
Published: July 2023

Uranium (U) is a well-known nephrotoxicant which forms precipitates in the lysosomes of renal proximal tubular epithelial cells (PTECs) after U-exposure at a cytotoxic dose. However, the roles of lysosomes in U decorporation and detoxification remain to be elucidated. Mucolipin transient receptor potential channel 1 (TRPML1) is a major lysosomal Ca2+channel regulating lysosomal exocytosis. We herein demonstrate that the delayed administration of the specific TRPML1 agonist ML-SA1 significantly decreases U accumulation in the kidney, mitigates renal proximal tubular injury, increases apical exocytosis of lysosomes and reduces lysosomal membrane permeabilization (LMP) in renal PTECs of male mice with single-dose U poisoning or multiple-dose U exposure. Mechanistic studies reveal that ML-SA1 stimulates intracellular U removal and reduces U-induced LMP and cell death through activating the positive TRPML1-TFEB feedback loop and consequent lysosomal exocytosis and biogenesis in U-loaded PTECs in vitro. Together, our studies demonstrate that TRPML1 activation is an attractive therapeutic strategy for the treatment of U-induced nephrotoxicity.
Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma
Authors: Fang Jie , Singh Shivendra , Cheng Changde , Natarajan Sivaraman , Sheppard Heather , Abu-Zaid Ahmed , Durbin Adam D. , Lee Ha Won , Wu Qiong , Steele Jacob , Connelly Jon P. , Jin Hongjian , Chen Wenan , Fan Yiping , Pruett-Miller Shondra M. , Rehg Jerold E. , Koo Selene C. , Santiago Teresa , Emmons Joseph , Cairo Stefano , Wang Ruoning , Glazer Evan S. , Murphy Andrew J. , Chen Taosheng , Davidoff Andrew M. , Armengol Carolina , Easton John , Chen Xiang , Yang Jun
Published: July 2023

A lack of relevant genetic models and cell lines hampers our understanding of hepatoblastoma pathogenesis and the development of new therapies for this neoplasm. Here, we report an improved MYC-driven hepatoblastoma-like murine model that recapitulates the pathological features of embryonal type of hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of the human disease. Single-cell RNA-sequencing and spatial transcriptomics identify distinct subpopulations of hepatoblastoma cells. After deriving cell lines from the mouse model, we map cancer dependency genes using CRISPR-Cas9 screening and identify druggable targets shared with human hepatoblastoma (e.g., CDK7, CDK9, PRMT1, PRMT5). Our screen also reveals oncogenes and tumor suppressor genes in hepatoblastoma that engage multiple, druggable cancer signaling pathways. Chemotherapy is critical for human hepatoblastoma treatment. A genetic mapping of doxorubicin response by CRISPR-Cas9 screening identifies modifiers whose loss-of-function synergizes with (e.g., PRKDC) or antagonizes (e.g., apoptosis genes) the effect of chemotherapy. The combination of PRKDC inhibition and doxorubicin-based chemotherapy greatly enhances therapeutic efficacy. These studies provide a set of resources including disease models suitable for identifying and validating potential therapeutic targets in human high-risk hepatoblastoma.
2D CdPS3-based versatile superionic conductors
Authors: Yu Xin , Ren Wencai
Published: July 2023

Ion transport in nanochannels is crucial for applications in life science, filtration, and energy storage. However, multivalent ion transport is more difficult than the monovalent analogues due to the steric effect and stronger interactions with channel walls, and the ion mobility decreases significantly as temperature decreases. Although many kinds of solid ionic conductors (SICs) have been developed, they can attain practically useful conductivities (0.01 S cm−1) only for monovalent ions above 0 °C. Here, we report a class of versatile superionic conductors, monolayer CdPS3 nanosheets-based membranes intercalated with diverse cations with a high density up to ∼2 nm−2. They exhibit unexpectedly similar superhigh ion conductivities for monovalent (K+, Na+, Li+) and multivalent ions (Ca2+, Mg2+, Al3+), ∼0.01 to 0.8 S cm−1 in the temperature range of −30 ‒ 90 °C, which are one to two orders of magnitude higher than those of the corresponding best SICs. We reveal that the high conductivity originates from the concerted movement of high-density cations in the well-ordered nanochannels with high mobility and low energy barrier. Our work opens an avenue for designing superionic conductors that can conduct various cations and provides possibilities for discovering unusual nanofluidic phenomena in nanocapillaries.
Tunably strained metallacycles enable modular differentiation of aza-arene C–H bonds
Authors: Xi Longlong , Wang Minyan , Liang Yong , Zhao Yue , Shi Zhuangzhi
Published: July 2023

The precise activation of C–H bonds will eventually provide chemists with transformative methods to access complex molecular architectures. Current approaches to selective C–H activation relying on directing groups are effective for the generation of five-membered, six-membered and even larger ring metallacycles but show narrow applicability to generate three- and four-membered rings bearing high ring strain. Furthermore, the identification of distinct small intermediates remains unsolved. Here, we developed a strategy to control the size of strained metallacycles in the rhodium-catalysed C−H activation of aza-arenes and applied this discovery to tunably incorporate the alkynes into their azine and benzene skeletons. By merging the rhodium catalyst with a bipyridine-type ligand, a three-membered metallacycle was obtained in the catalytic cycle, while utilizing an NHC ligand favours the generation of the four-membered metallacycle. The generality of this method was demonstrated with a range of aza-arenes, such as quinoline, benzo[f]quinolone, phenanthridine, 4,7-phenanthroline, 1,7-phenanthroline and acridine. Mechanistic studies revealed the origin of the ligand-controlled regiodivergence in the strained metallacycles.
Interplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability
Authors: Movert Elin , Bolarin Jaume Salgado , Valfridsson Christine , Velarde Jorge , Skrede Steinar , Nekludov Michael , Hyldegaard Ole , Arnell Per , Svensson Mattias , Norrby-Teglund Anna , Cho Kyu Hong , Elhaik Eran , Wessels Michael R. , Råberg Lars , Carlsson Fredric
Published: July 2023

Variability in disease severity caused by a microbial pathogen is impacted by each infection representing a unique combination of host and pathogen genomes. Here, we show that the outcome of invasive Streptococcus pyogenes infection is regulated by an interplay between human STING genotype and bacterial NADase activity. S. pyogenes-derived c-di-AMP diffuses via streptolysin O pores into macrophages where it activates STING and the ensuing type I IFN response. However, the enzymatic activity of the NADase variants expressed by invasive strains suppresses STING-mediated type I IFN production. Analysis of patients with necrotizing S. pyogenes soft tissue infection indicates that a STING genotype associated with reduced c-di-AMP-binding capacity combined with high bacterial NADase activity promotes a ‘perfect storm’ manifested in poor outcome, whereas proficient and uninhibited STING-mediated type I IFN production correlates with protection against host-detrimental inflammation. These results reveal an immune-regulating function for bacterial NADase and provide insight regarding the host-pathogen genotype interplay underlying invasive infection and interindividual disease variability.
Unbiased proteomics and multivariable regularized regression techniques identify SMOC1, NOG, APCS, and NTN1 in an Alzheimer’s disease brain proteomic signature
Authors: Roberts Jackson A. , Varma Vijay R. , Candia Julián , Tanaka Toshiko , Ferrucci Luigi , Bennett David A. , Thambisetty Madhav
Published: July 2023

Advancements in omics methodologies have generated a wealth of high-dimensional Alzheimer’s disease (AD) datasets, creating significant opportunities and challenges for data interpretation. In this study, we utilized multivariable regularized regression techniques to identify a reduced set of proteins that could discriminate between AD and cognitively normal (CN) brain samples. UtilizingeNetXplorer, an R package that tests the accuracy and significance of a family of elastic net generalized linear models, we identified 4 proteins (SMOC1, NOG, APCS, NTN1) that accurately discriminated between AD (n = 31) and CN (n = 22) middle frontal gyrus (MFG) tissue samples from Religious Orders Study participants with 83 percent accuracy. We then validated this signature in MFG samples from Baltimore Longitudinal Study of Aging participants using leave-one-out logistic regression cross-validation, finding that the signature again accurately discriminated AD (n = 31) and CN (n = 19) participants with a receiver operating characteristic curve area under the curve of 0.863. These proteins were strongly correlated with the burden of neurofibrillary tangle and amyloid pathology in both study cohorts. We additionally tested whether these proteins differed between AD and CN inferior temporal gyrus (ITG) samples and blood serum samples at the time of AD diagnosis in ROS and BLSA, finding that the proteins differed between AD and CN ITG samples but not in blood serum samples. The identified proteins may provide mechanistic insights into the pathophysiology of AD, and the methods utilized in this study may serve as the basis for further work with additional high-dimensional datasets in AD.
Design of allosteric sites into rotary motor V1-ATPase by restoring lost function of pseudo-active sites
Authors: Kosugi Takahiro , Iida Tatsuya , Tanabe Mikio , Iino Ryota , Koga Nobuyasu
Published: July 2023

Allostery produces concerted functions of protein complexes by orchestrating the cooperative work between the constituent subunits. Here we describe an approach to create artificial allosteric sites in protein complexes. Certain protein complexes contain subunits with pseudo-active sites, which are believed to have lost functions during evolution. Our hypothesis is that allosteric sites in such protein complexes can be created by restoring the lost functions of pseudo-active sites. We used computational design to restore the lost ATP-binding ability of the pseudo-active site in the B subunit of a rotary molecular motor, V1-ATPase. Single-molecule experiments with X-ray crystallography analyses revealed that binding of ATP to the designed allosteric site boosts this V1’s activity compared with the wild-type, and the rotation rate can be tuned by modulating ATP’s binding affinity. Pseudo-active sites are widespread in nature, and our approach shows promise as a means of programming allosteric control over concerted functions of protein complexes.
The historical social cost of fossil and industrial CO2 emissions
Authors: Rickels Wilfried , Meier Felix , Quaas Martin
Published: July 2023

Past CO2 emissions have been causing social costs and continue to reduce wealth in the future. Countries differ considerably in their amounts and time profiles of past CO2 emissions. Here we calibrate an integrated assessment model on past economic and climate development to estimate the historical time series of social costs of carbon and to assess how much individual countries have reduced global wealth by their fossil and industrial-process CO2 emissions from 1950 to 2018. Historical social costs of carbon quantify the long-lasting wealth reduction by past CO2 emissions, which we term ‘climate wealth borrowing’, as economic output has been generated at the expense of future climate damages. We find that the United States and China have been responsible for the largest shares of global climate wealth borrowing since 1950, while the per-capita pattern is quite different.
Identifying species likely threatened by international trade on the IUCN Red List can inform CITES trade measures
Authors: Challender Daniel W. S. , Cremona Patricia J. , Malsch Kelly , Robinson Janine E. , Pavitt Alyson T. , Scott Janet , Hoffmann Rachel , Joolia Ackbar , Oldfield Thomasina E. E. , Jenkins Richard K. B. , Conde Dalia A. , Hilton-Taylor Craig , Hoffmann Michael
Published: July 2023

Overexploitation is a major threat to biodiversity and international trade in many species is regulated through the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). However, there is no established method to systematically determine which species are most at risk from international trade to inform potential trade measures under CITES. Here, we develop a mechanism using the International Union for Conservation of Nature’s Red List of Threatened Species to identify species that are likely to be threatened by international trade. Of 2,211 such species, CITES includes 59% (1,307 species), leaving two-fifths overlooked and in potential need of international trade regulation. Our results can inform deliberations on potential proposals to revise trade measures for species at CITES Conference of the Parties meetings. We also show that, for taxa with biological resource use documented as a threat, the number of species threatened by local and national use is four times greater than species likely threatened by international trade. To effectively address the overexploitation of species, interventions focused on achieving sustainability in international trade need to be complemented by commensurate measures to ensure that local and national use and trade of wildlife is well-regulated and sustainable.
Widespread shallow mesoscale circulations observed in the trades
Authors: George Geet , Stevens Bjorn , Bony Sandrine , Vogel Raphaela , Naumann Ann Kristin
Published: July 2023

Understanding the drivers of cloud organization is crucial for accurately estimating cloud feedbacks and their contribution to climate warming. Shallow mesoscale circulations are thought to play an important role in cloud organization, but they have not been observed. Here we present observational evidence for the existence of shallow mesoscale overturning circulations using divergence measurements made during the EUREC4A field campaign in the North Atlantic trades. Meteorological re-analyses reproduce the observed low-level divergence well and confirm the circulations to be mesoscale features (around 200 km across). We find that the shallow mesoscale circulations are associated with large variability in mesoscale vertical velocity and amplify moisture variance at the cloud base. Through their modulation of cloud-base moisture, the circulations influence how efficiently the subcloud layer dries, thus producing moist ascending branches and dry descending branches. The observed moisture variance differs from expectations from large-eddy simulations, which show the largest variance near the cloud top and negligible subcloud variance. The ubiquity of shallow mesoscale circulations, and their coupling to moisture and cloud fields, suggests that the strength and scale of mesoscale circulations are integral to determining how clouds respond to climate change.
Light-induced hexatic state in a layered quantum material
Authors: Domröse Till , Danz Thomas , Schaible Sophie F. , Rossnagel Kai , Yalunin Sergey V. , Ropers Claus
Published: July 2023

The tunability of materials properties by light promises a wealth of future applications in energy conversion and information technology. Strongly correlated materials such as transition metal dichalcogenides offer optical control of electronic phases, charge ordering and interlayer correlations by photodoping. Here, we find the emergence of a transient hexatic state during the laser-induced transformation between two charge-density wave phases in a thin-film transition metal dichalcogenide, 1T-type tantalum disulfide (1T-TaS2). Introducing tilt-series ultrafast nanobeam electron diffraction, we reconstruct charge-density wave rocking curves at high momentum resolution. An intermittent suppression of three-dimensional structural correlations promotes a loss of in-plane translational order caused by a high density of unbound topological defects, characteristic of a hexatic intermediate. Our results demonstrate the merit of tomographic ultrafast structural probing in tracing coupled order parameters, heralding universal nanoscale access to laser-induced dimensionality control in functional heterostructures and devices.
Hole-limited electrochemical doping in conjugated polymers
Authors: Keene Scott T. , Laulainen Joonatan E. M. , Pandya Raj , Moser Maximilian , Schnedermann Christoph , Midgley Paul A. , McCulloch Iain , Rao Akshay , Malliaras George G.
Published: July 2023

Simultaneous transport and coupling of ionic and electronic charges is fundamental to electrochemical devices used in energy storage and conversion, neuromorphic computing and bioelectronics. While the mixed conductors enabling these technologies are widely used, the dynamic relationship between ionic and electronic transport is generally poorly understood, hindering the rational design of new materials. In semiconducting electrodes, electrochemical doping is assumed to be limited by motion of ions due to their large mass compared to electrons and/or holes. Here, we show that this basic assumption does not hold for conjugated polymer electrodes. Using operando optical microscopy, we reveal that electrochemical doping speeds in a state-of-the-art polythiophene can be limited by poor hole transport at low doping levels, leading to substantially slower switching speeds than expected. We show that the timescale of hole-limited doping can be controlled by the degree of microstructural heterogeneity, enabling the design of conjugated polymers with improved electrochemical performance.
Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia
Authors: Anderson Nathaniel D. , Birch Jack , Accogli Theo , Criado Ignacio , Khabirova Eleonora , Parks Conor , Wood Yvette , Young Matthew D. , Porter Tarryn , Richardson Rachel , Albon Sarah J. , Popova Bilyana , Lopes Andre , Wynn Robert , Hough Rachael , Gohil Satyen H. , Pule Martin , Amrolia Persis J. , Behjati Sam , Ghorashian Sara
Published: July 2023

In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists.
A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease
Authors: Patel Aniruddh P. , Wang Minxian , Ruan Yunfeng , Koyama Satoshi , Clarke Shoa L. , Yang Xiong , Tcheandjieu Catherine , Agrawal Saaket , Fahed Akl C. , Ellinor Patrick T. ,   Genes & Health Research Team; the Million Veteran Program, Tsao Philip S. , Sun Yan V. , Cho Kelly , Wilson Peter W. F. , Assimes Themistocles L. , van Heel David A. , Butterworth Adam S. , Aragam Krishna G. , Natarajan Pradeep , Khera Amit V.
Published: July 2023

Identification of individuals at highest risk of coronary artery disease (CAD)—ideally before onset—remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMultstrongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10–2.19,P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMultwas also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70–1.76,P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMultdemonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMultfor CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.
Single cell transcriptome sequencing of stimulated and frozen human peripheral blood mononuclear cells
Authors: Derbois Céline , Palomares Marie-Ange , Deleuze Jean-François , Cabannes Eric , Bonnet Eric
Published: July 2023

Peripheral blood mononuclear cells (PBMCs) are blood cells that are a critical part of the immune system used to fight off infection, defending our bodies from harmful pathogens. In biomedical research, PBMCs are commonly used to study global immune response to disease outbreak and progression, pathogen infections, for vaccine development and a multitude of other clinical applications. Over the past few years, the revolution in single-cell RNA sequencing (scRNA-seq) has enabled an unbiased quantification of gene expression in thousands of individual cells, which provides a more efficient tool to decipher the immune system in human diseases. In this work, we generate scRNA-seq data from human PBMCs at high sequencing depth (>100,000 reads/cell) for more than 30,000 cells, in resting, stimulated, fresh and frozen conditions. The data generated can be used for benchmarking batch correction and data integration methods, and to study the effect of freezing-thawing cycles on the quality of immune cell populations and their transcriptomic profiles.
Causal associations between inflammatory bowel disease and primary biliary cholangitis: a two-sample bidirectional Mendelian randomization study
Authors: Zhao Jiaxi , Li Kaixin , Liao Xiaoyang , Zhao Qian
Published: July 2023

Inflammatory bowel disease (IBD) has been reported to be associated with hepatobiliary diseases. Previous observational and Mendelian randomization (MR) studies have suggested a causal association between IBD and primary sclerosing cholangitis (PSC). However, it is unclear whether IBD has a causal association with primary biliary cholangitis (PBC): another autoimmune liver disease. We obtained genome-wide association study (GWAS) statistics from published GWASs for PBC, UC, and CD. We screened qualified instrumental variables (IVs) based on the three major assumptions of MR. To determine the causal relationships between UC or CD and PBC, two-sample MR analyses were performed using inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods, and sensitivity analyses were conducted to validate the robustness of the results. We also conducted reverse MR analysis to reveal the causal association between PBC and UC or CD. UC was associated with a higher risk of PBC (OR 1.35, 95% CI 1.05–1.73, P = 0.02) in the IVW method, and CD was associated with an increased risk of PBC (OR 1.18, 95% CI 1.03–1.36, P = 0.02) in IVW. The weighted median and MR-Egger regression of both diseases showed a consistent direction but were not statistically significant. Results of the reverse MR analysis did not suggest genetic susceptibility that PBC was associated with an increased risk of UC (OR 1.05, 95% CI 0.95–1.17, P = 0.34) or CD (OR 1.1, 95% CI 0.99–1.20, P = 0.06). The present study revealed that IBD subtypes could increase the incidence of PBC, but in turn, PBC did not increase the incidence of IBD subtypes. Understanding that IBD and PBC constitute mutual risk factors can help with the clinical management of both diseases.
Amelogenin peptide analyses reveal female leadership in Copper Age Iberia (c. 2900–2650 BC)
Authors: Cintas-Peña Marta , Luciañez-Triviño Miriam , Montero Artús Raquel , Bileck Andrea , Bortel Patricia , Kanz Fabian , Rebay-Salisbury Katharina , García Sanjuán Leonardo
Published: July 2023

Given the absence of written records, the main source of information available to analyze gender inequalities in early complex societies is the human body itself. And yet, for decades, archaeologists have struggled with the sex estimation of poorly preserved human remains. Here we present an exceptional case study that shows how ground-breaking new scientific methods may address this problem. Through the analysis of sexually dimorphic amelogenin peptides in tooth enamel, we establish that the most socially prominent person of the Iberian Copper Age (c. 3200–2200 BC) was not male, as previously thought, but female. The analysis of this woman, discovered in 2008 at Valencina, Spain, reveals that she was a leading social figure at a time where no male attained a remotely comparable social position. Only other women buried a short time after in the Montelirio tholos, part of the same burial area, appear to have enjoyed a similarly high social position. Our results invite to reconsider established interpretations about the political role of women at the onset of early social complexity, and question traditionally held views of the past. Furthermore, this study anticipates the changes that newly developed scientific methods may bring to prehistoric archaeology and the study of human social evolution.
The neurobiological effects of mind–body exercise: a systematic review and meta-analysis of neuroimaging studies
Authors: Han Yvonne M. Y. , Chan Melody M. Y. , Choi Coco X. T. , Law Maxwell C. H. , Ahorsu Daniel Kwasi , Tsang Hector W. H.
Published: July 2023

The neurobiological effects of mind–body exercise on brain activation, functional neural connections and structural changes in the brain remain elusive. This systematic review and coordinate-based meta-analysis investigated the changes in resting-state and task-based brain activation, as well as structural brain changes before and after mind–body exercise compared to waitlist or active controls based on published structural or functional magnetic resonance imaging randomized controlled trials or cross-sectional studies. Electronic database search and manual search in relevant publications yielded 34 empirical studies with low-to-moderate risk of bias (assessed by Cochrane risk-of-bias tool for randomized trials or Joanna Briggs Institute’s critical appraisal checklist for analytical cross-sectional studies) that fulfilled the inclusion criteria, with 26 studies included in the narrative synthesis and 8 studies included in the meta-analysis. Coordinate-based meta-analysis showed that, while mind–body exercise enhanced the activation of the left anterior cingulate cortex within the default mode network (DMN), it induced more deactivation in the left supramarginal gyrus within the ventral attention network (uncorrected ps < 0.05). Meta-regression with duration of mind–body practice as a factor showed that, the activation of right inferior parietal gyrus within the DMN showed a positive association with increasing years of practice (voxel-corrected p < 0.005). Although mind–body exercise is shown to selectively modulate brain functional networks supporting attentional control and self-awareness, the overall certainty of evidence is limited by small number of studies. Further investigations are needed to understand the effects of both short-term and long-term mind–body exercise on structural changes in the brain.

PROSPERO registration number: CRD42021248984.
A mindful approach to controlling intrusive thoughts
Authors: Ashton S. M. , Sambeth A. , Quaedflieg C. W. E. M.
Published: July 2023

Intrusive thoughts of negative experiences can pose a threat to our well-being. To some extent, unwanted memories can be intentionally controlled via an executive control mechanism that downregulates the occurrence of intrusions. Mindfulness training can improve executive control. It is not known whether mindfulness training can be used as an intervention to improve intentional memory control and reduce intrusions. To this end, 148 healthy participants completed a 10-day app-based mindfulness training or an active control task. At baseline, inhibitory control and working memory were assessed as measures of executive functioning. Post-mindfulness training, intrusions were assessed via the Think/No-Think task. It was expected that mindfulness training would reduce intrusions. Furthermore, we hypothesised that this would be moderated by baseline executive functioning. Results revealed that, contrary to our hypothesis, both groups increased equally in dispositional mindfulness between baseline and post-test. As such, our exploratory analysis revealed that higher dispositional mindfulness across both groups resulted in fewer intrusions and enhanced the ability to downregulate intrusions over time. Furthermore, this effect was moderated by inhibitory control at baseline. These results provide insight into factors that can improve the ability to control unwanted memories, which could have considerable implications for treatments in psychopathologies characterized by the frequent occurrence of intrusive thoughts.

Protocol registration

The stage 1 protocol for this Registered Report was accepted in principle on 11th March, 2022. The protocol, as accepted by the journal, can be found at:https://doi.org/10.17605/OSF.IO/U8SJN.
Hybridization of the swarming and interior point algorithms to solve the Rabinovich–Fabrikant system
Authors: Sabir Zulqurnain , Said Salem Ben , Al-Mdallal Qasem
Published: July 2023

In this study, a trustworthy swarming computing procedure is demonstrated for solving the nonlinear dynamics of the Rabinovich–Fabrikant system. The nonlinear system’s dynamic depends upon the three differential equations. The computational stochastic structure based on the artificial neural networks (ANNs) along with the optimization of global search swarming particle swarm optimization (PSO) and local interior point (IP) algorithms, i.e., ANNs-PSOIP is presented to solve the Rabinovich–Fabrikant system. An objective function based on the differential form of the model is optimized through the local and global search methods. The correctness of the ANNs-PSOIP scheme is observed through the performances of achieved and source solutions, while the negligible absolute error that is around 10−05–10−07 also represent the worth of the ANNs-PSOIP algorithm. Furthermore, the consistency of the ANNs-PSOIP scheme is examined by applying different statistical procedures to solve the Rabinovich–Fabrikant system.