bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic Propagation in the Near‐Surface Martian Atmosphere
Authors: Gillier Martin , Petculescu Andi , Stott Alexander E. , Murdoch Naomi , Jacob Xavier , Chide Baptiste , Maurice Sylvestre , Mimoun David
Published: July 2024

This work introduces a comprehensive model of sound propagation on Mars, in light of the recent operation of several microphones on the Martian surface. The main outcome of this work is an operational acoustic model capable of simulating the sound field created by any source, at any location on the Martian surface, at any time. Expanding on the result of previous work (Gillier et al., 2024, https://doi.org/10.1029/2023je008257), we use the parabolic equation method for sound propagation in order to obtain the overall sound field produced by a source, in a given atmospheric composition and state, and accounting for ground properties. The resulting model enables the study of acoustics on Mars, and has the potential also to be used to probe the properties of the Martian environment using acoustic measurements with known sources. We investigate the effects of the Martian ground and the vertical profile of temperature and wind, on sound propagation. We find that the ground has a minor effect on sound propagation, and the wind profile strongly influences sound propagation as on Earth. However, the midday near surface temperature profiles on Mars are shown to cause refraction, which generates non‐negligible acoustic losses that are an order of magnitude stronger than typical refraction‐related acoustic losses on Earth. We show that the effect of the Martian atmospheric turbulence is to slightly reduce the acoustic losses due to refraction. Finally, we apply our model to show that refraction and atmospheric turbulence have a negligible effect on the propagation of sound from Ingenuity to the Perseverance rover.
A mixed meal tolerance test predicts onset of type 2 diabetes in Southwestern Indigenous adults
Authors: Mitchell Cassie M. , Stinson Emma J. , Chang Douglas C. , Krakoff Jonathan
Published: July 2024

Background/Objective

To identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT).

Methods

Adult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC).

Results

At follow-up (median time 9.6 [inter-quartile range: 5.6–13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes.

Conclusions

Glucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk.

Clinical Trial Registry

ClinicalTrials.gov identifier : NCT00340132, NCT00339482
Immune dysfunction prior to and during vaccination in multiple myeloma: a case study based on COVID-19
Authors: Martín-Sánchez Esperanza , Tamariz-Amador Luis-Esteban , Guerrero Camila , Zherniakova Anastasiia , Zabaleta Aintzane , Maia Catarina , Blanco Laura , Alignani Diego , Fortuño Maria-Antonia , Grande Carlos , Manubens Andrea , Arguiñano Jose-Maria , Gomez Clara , Perez-Persona Ernesto , Olazabal Iñigo , Oiartzabal Itziar , Panizo Carlos , Prosper Felipe , San-Miguel Jesus F. , Rodriguez-Otero Paula , Paiva Bruno ,   the Asociación Vasco-Navarra de Hematología y Hemoterapia (ASOVASNA) cooperative group, San Miguel Jesus F.
Published: July 2024

Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4+ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8+ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions
Authors: Zhong Yan , Liu Jingfeng
Published: July 2024

Cancer immunotherapy harnesses the body’s immune system to combat malignancies, building upon an understanding of tumor immunosurveillance and immune evasion mechanisms. This therapeutic approach reactivates anti-tumor immune responses and can be categorized into active, passive, and combined immunization strategies. Active immunotherapy engages the immune system to recognize and attack tumor cells by leveraging host immunity with cytokine supplementation or vaccination. Conversely, passive immunotherapy employs exogenous agents, such as monoclonal antibodies (anti-CTLA4, anti-PD1, anti-PD-L1) or adoptive cell transfers (ACT) with genetically engineered chimeric antigen receptor (CAR) T or NK cells, to exert anti-tumor effects. Over the past decades, CAR-T cell therapies have gained significant traction in oncological treatment, offering hope through their targeted approach. However, the potential adverse effects associated with CAR-T cells, including cytokine release syndrome (CRS), off-tumor toxicity, and neurotoxicity, warrant careful consideration. Recently, CAR-NK cell therapy has emerged as a promising alternative in the landscape of tumor immunotherapy, distinguished by its innate advantages over CAR-T cell modalities. In this review, we will synthesize the latest research and clinical advancements in CAR-NK cell therapies. We will elucidate the therapeutic benefits of employing CAR-NK cells in oncology and critically examine the developmental bottlenecks impeding their broader application. Our discussion aims to provide a comprehensive overview of the current status and future potential of CAR-NK cells in cancer immunotherapy.
Depressive symptoms as risk factors for the onset of home hypertension: a prospective cohort study
Authors: Tokioka Sayuri , Nakaya Naoki , Hatanaka Rieko , Nakaya Kumi , Kogure Mana , Chiba Ippei , Nochioka Kotaro , Metoki Hirohito , Murakami Takahisa , Satoh Michihiro , Nakamura Tomohiro , Ishikuro Mami , Obara Taku , Hamanaka Yohei , Orui Masatsugu , Kobayashi Tomoko , Uruno Akira , Kodama Eiichi N. , Nagaie Satoshi , Ogishima Soichi , Izumi Yoko , Fuse Nobuo , Kuriyama Shinichi , Hozawa Atsushi
Published: July 2024

Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02–1.84), 1.18 (95% CI: 0.86–1.61), and 1.66 (95% CI: 1.17–2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension.
Multiscale chemogenetic dissection of fronto-temporal top-down regulation for object memory in primates
Authors: Hirabayashi Toshiyuki , Nagai Yuji , Hori Yuki , Hori Yukiko , Oyama Kei , Mimura Koki , Miyakawa Naohisa , Iwaoki Haruhiko , Inoue Ken-ichi , Suhara Tetsuya , Takada Masahiko , Higuchi Makoto , Minamimoto Takafumi
Published: July 2024

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.
Strong angular and spectral narrowing of electroluminescence in an integrated Tamm-plasmon-driven halide perovskite LED
Authors: Ooi Zher Ying , Jiménez-Solano Alberto , Gałkowski Krzysztof , Sun Yuqi , Ferrer Orri Jordi , Frohna Kyle , Salway Hayden , Kahmann Simon , Nie Shenyu , Vega Guadalupe , Kar Shaoni , Nowak Michał P. , Maćkowski Sebastian , Nyga Piotr , Ducati Caterina , Greenham Neil C. , Lotsch Bettina V. , Anaya Miguel , Stranks Samuel D.
Published: July 2024

Next-generation light-emitting applications such as displays and optical communications require judicious control over emitted light, including intensity and angular dispersion. To date, this remains a challenge as conventional methods require cumbersome optics. Here, we report highly directional and enhanced electroluminescence from a solution-processed quasi-2-dimensional halide perovskite light-emitting diode by building a device architecture to exploit hybrid plasmonic-photonic Tamm plasmon modes. By exploiting the processing and bandgap tunability of the halide perovskite device layers, we construct the device stack to optimise both optical and charge-injection properties, leading to narrow forward electroluminescence with an angular full-width half-maximum of 36.6° compared with the conventional isotropic control device of 143.9°, and narrow electroluminescence spectral full-width half-maximum of 12.1 nm. The device design is versatile and tunable to work with emission lines covering the visible spectrum with desired directionality, thus providing a promising route to modular, inexpensive, and directional operating light-emitting devices.
Pneumococcal competence is a populational health sensor driving multilevel heterogeneity in response to antibiotics
Authors: Prudhomme Marc , Johnston Calum H. G. , Soulet Anne-Lise , Boyeldieu Anne , De Lemos David , Campo Nathalie , Polard Patrice
Published: July 2024

Competence for natural transformation is a central driver of genetic diversity in bacteria. In the human pathogen Streptococcus pneumoniae, competence exhibits a populational character mediated by the stress-induced ComABCDE quorum-sensing (QS) system. Here, we explore how this cell-to-cell communication mechanism proceeds and the functional properties acquired by competent cells grown under lethal stress. We show that populational competence development depends on self-induced cells stochastically emerging in response to stresses, including antibiotics. Competence then propagates through the population from a low threshold density of self-induced cells, defining a biphasic Self-Induction and Propagation (SI&P) QS mechanism. We also reveal that a competent population displays either increased sensitivity or improved tolerance to lethal doses of antibiotics, dependent in the latter case on the competence-induced ComM division inhibitor. Remarkably, these surviving competent cells also display an altered transformation potential. Thus, the unveiled SI&P QS mechanism shapes pneumococcal competence as a health sensor of the clonal population, promoting a bet-hedging strategy that both responds to and drives cells towards heterogeneity.
Recurrent evolution of adhesive defence systems in amphibians by parallel shifts in gene expression
Authors: Zaman Shabnam , Lengerer Birgit , Van Lindt Joris , Saenen Indra , Russo Giorgio , Bossaer Laura , Carpentier Sebastien , Tompa Peter , Flammang Patrick , Roelants Kim
Published: July 2024

Natural selection can drive organisms to strikingly similar adaptive solutions, but the underlying molecular mechanisms often remain unknown. Several amphibians have independently evolved highly adhesive skin secretions (glues) that support a highly effective antipredator defence mechanism. Here we demonstrate that the glue of the Madagascan tomato frog, Dyscophus guineti, relies on two interacting proteins: a highly derived member of a widespread glycoprotein family and a galectin. Identification of homologous proteins in other amphibians reveals that these proteins attained a function in skin long before glues evolved. Yet, major elevations in their expression, besides structural changes in the glycoprotein (increasing its structural disorder and glycosylation), caused the independent rise of glues in at least two frog lineages. Besides providing a model for the chemical functioning of animal adhesive secretions, our findings highlight how recruiting ancient molecular templates may facilitate the recurrent evolution of functional innovations.
Computational elements based on coupled VO2 oscillators via tunable thermal triggering
Authors: Li Guanmin , Wang Zhong , Chen Yuliang , Jeon Jae-Chun , Parkin Stuart S. P.
Published: July 2024

Computational technologies based on coupled oscillators are of great interest for energy efficient computing. A key to developing such technologies is the tunable control of the interaction among oscillators which today is accomplished by additional electronic components. Here we show that the synchronization of closely spaced vanadium dioxide (VO2) oscillators can be controlled via a simple thermal triggering element that itself is formed from VO2. The net energy consumed by the oscillators is lower during thermal coupling compared with the situation where they are oscillating independently. As the size of the oscillator shrinks from 6 μm to 200 nm both the energy efficiency and the oscillator frequency increases. Based on such oscillators with active tuning, we demonstrate AND, NAND, and NOR logic gates and various firing patterns that mimic the behavior of spiking neurons. Our findings demonstrate an innovative approach towards computational techniques based on networks of thermally coupled oscillators.
Ambient hydrogenation of solid aromatics enabled by a high entropy alloy nanocatalyst
Authors: Jing Zekun , Guo Yakun , Wang Qi , Yan Xinrong , Yue Guozong , Li Zhendong , Liu Hanwen , Qin Ruixuan , Zhong Changyin , Li Mingzhen , Xu Dingguo , Yao Yunxi , Yao Yonggang , Shuai Maobing
Published: July 2024

Hydrogenation is a versatile chemical process with significant applications in various industries, including food production, petrochemical refining, pharmaceuticals, and hydrogen carriers/safety. Traditional hydrogenation of aromatics, hindered by the stable π-conjugated phenyl ring structures, typically requires high temperatures and pressures, making ambient hydrogenation a grand challenge. Herein, we introduce a PdPtRuCuNi high entropy alloy (HEA) nanocatalyst, achieving an exceptional 100% hydrogenation of carbon-carbon unsaturated bonds, including alkynyl and phenyl groups, in solid 1,4-bis(phenylethynyl)benzene (DEB) at 25 °C under ≤1 bar H2 and solventless condition. This results in a threefold higher hydrogen uptake for DEB-contained composites compared to conventional Pd catalysts, which can only hydrogenate the alkynyl groups with a ~ 27% conversion of DEB. Our experimental results, complemented by theoretical calculations, reveal that PdPtRu alloy is highly active and crucial in enabling the hydrogenation of phenyl groups, while all five elements work synergistically to regulate the reaction rate. Remarkably, this newly developed catalyst also achieves nearly 100% reactivity for ambient hydrogenation of a broad range of aromatics, suggesting its universal effectiveness. Our research uncovers a novel material platform and catalyst design principle for efficient and general hydrogenation. The multi-element synergy in HEA also promises unique catalytic behaviors beyond hydrogenation applications.
FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs
Authors: Wasserman Jason S. , Faezov Bulat , Patel Kishan R. , Kurimchak Alison M. , Palacio Seren M. , Glass David J. , Fowle Holly , McEwan Brennan C. , Xu Qifang , Zhao Ziran , Cressey Lauren , Johnson Neil , Duncan James S. , Kettenbach Arminja N. , Dunbrack Roland L. , Graña Xavier
Published: July 2024

The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase.
Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells
Authors: Donnelly Hannah , Ross Ewan , Xiao Yinbo , Hermantara Rio , Taqi Aqeel F. , Doherty-Boyd W. Sebastian , Cassels Jennifer , Tsimbouri Penelope. M. , Dunn Karen M. , Hay Jodie , Cheng Annie , Meek R. M. Dominic , Jain Nikhil , West Christopher , Wheadon Helen , Michie Alison M. , Peault Bruno , West Adam G. , Salmeron-Sanchez Manuel , Dalby Matthew J.
Published: July 2024

Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.
HLTF disrupts Cas9-DNA post-cleavage complexes to allow DNA break processing
Authors: Reginato Giordano , Dello Stritto Maria Rosaria , Wang Yanbo , Hao Jingzhou , Pavani Raphael , Schmitz Michael , Halder Swagata , Morin Vincent , Cannavo Elda , Ceppi Ilaria , Braunshier Stefan , Acharya Ananya , Ropars Virginie , Charbonnier Jean-Baptiste , Jinek Martin , Nussenzweig Andrè , Ha Taekjip , Cejka Petr
Published: July 2024

The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3′-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.
Robust trigger wave speed in Xenopus cytoplasmic extracts
Authors: Huang Jo-Hsi , Chen Yuping , Huang William Y. C. , Tabatabaee Saman , Ferrell James E.
Published: July 2024

Self-regenerating trigger waves can spread rapidly through the crowded cytoplasm without diminishing in amplitude or speed, providing consistent, reliable, long-range communication. The macromolecular concentration of the cytoplasm varies in response to physiological and environmental fluctuations, raising the question of how or if trigger waves can robustly operate in the face of such fluctuations. Using Xenopus extracts, we find that mitotic and apoptotic trigger wave speeds are remarkably invariant. We derive a model that accounts for this robustness and for the eventual slowing at extremely high and low cytoplasmic concentrations. The model implies that the positive and negative effects of cytoplasmic concentration (increased reactant concentration vs. increased viscosity) are nearly precisely balanced. Accordingly, artificially maintaining a constant cytoplasmic viscosity during dilution abrogates this robustness. The robustness in trigger wave speeds may contribute to the reliability of the extremely rapid embryonic cell cycle.
Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis
Authors: Zheng Yu , Sakai Katsuyuki , Watanabe Kohei , Takagi Hiroshi , Sato-Shiozaki Yumi , Misumi Yuko , Miyanoiri Yohei , Kurisu Genji , Nogawa Toshihiko , Takita Ryo , Takahashi Shunji
Published: July 2024

To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins. Through iron atom substitution by Lewis acidic gallium (Ga) iron and computational calculations, we confirm that the ubiquitous Fe-S cluster efficiently functions as Lewis acid to accelerate the tandem [4+2] cycloaddition and Michael addition reactions by lowering free energy barriers. Our work highlights Nature’s ingenious strategy to generate complex molecule structures using the ubiquitous Fe-S protein. Furthermore, our study sheds light on the future design of Fd as a versatile Lewis acid catalyst for [4+2] cycloaddition reactions.
Disruption of Plasmodium falciparum kinetochore proteins destabilises the nexus between the centrosome equivalent and the mitotic apparatus
Authors: Li Jiahong , Shami Gerald J. , Liffner Benjamin , Cho Ellie , Braet Filip , Duraisingh Manoj T. , Absalon Sabrina , Dixon Matthew W. A. , Tilley Leann
Published: July 2024

Plasmodium falciparum is the causative agent of malaria and remains a pathogen of global importance. Asexual blood stage replication, via a process called schizogony, is an important target for the development of new antimalarials. Here we use ultrastructure-expansion microscopy to probe the organisation of the chromosome-capturing kinetochores in relation to the mitotic spindle, the centriolar plaque, the centromeres and the apical organelles during schizont development. Conditional disruption of the kinetochore components, PfNDC80 and PfNuf2, is associated with aberrant mitotic spindle organisation, disruption of the centromere marker, CENH3 and impaired karyokinesis. Surprisingly, kinetochore disruption also leads to disengagement of the centrosome equivalent from the nuclear envelope. Severing the connection between the nucleus and the apical complex leads to the formation of merozoites lacking nuclei. Here, we show that correct assembly of the kinetochore/spindle complex plays a previously unrecognised role in positioning the nascent apical complex in developing P. falciparum merozoites.
Tunable quantum emitters on large-scale foundry silicon photonics
Authors: Larocque Hugo , Buyukkaya Mustafa Atabey , Errando-Herranz Carlos , Papon Camille , Harper Samuel , Tao Max , Carolan Jacques , Lee Chang-Min , Richardson Christopher J. K. , Leake Gerald L. , Coleman Daniel J. , Fanto Michael L. , Waks Edo , Englund Dirk
Published: July 2024

Controlling large-scale many-body quantum systems at the level of single photons and single atomic systems is a central goal in quantum information science and technology. Intensive research and development has propelled foundry-based silicon-on-insulator photonic integrated circuits to a leading platform for large-scale optical control with individual mode programmability. However, integrating atomic quantum systems with single-emitter tunability remains an open challenge. Here, we overcome this barrier through the hybrid integration of multiple InAs/InP microchiplets containing high-brightness infrared semiconductor quantum dot single photon emitters into advanced silicon-on-insulator photonic integrated circuits fabricated in a 300 mm foundry process. With this platform, we achieve single-photon emission via resonance fluorescence and scalable emission wavelength tunability. The combined control of photonic and quantum systems opens the door to programmable quantum information processors manufactured in leading semiconductor foundries.
Ultrathin silica-tiling on living cells for chemobiotic catalysis
Authors: Oh Jeongsang , Kumari Nitee , Kim Dayeong , Kumar Amit , Lee In Su
Published: July 2024

Harnessing the power of cell biocatalysis for sustainable chemical synthesis requires rational integration of living cells with the modern synthetic catalysts. Here, we develop silica-tiling strategy that constructs a hierarchical, inorganic, protocellular confined nanospace around the individual living cell to accommodate molecularly accessible abiotic catalytic sites. This empowers the living microorganisms for new-to-nature chemical synthesis without compromising the cellular regenerative process. Yeast cell, a widely used biocatalyst, is upgraded via highly controlled self-assembly of 2D-bilayer silica-based catalytic modules on cell surfaces, opening the avenues for diverse chemobiotic reactions. For example, combining [AuPt]-catalyzed NADH regeneration, light-induced [Pd]-catalyzed C-C cross-coupling or lipase-catalyzed esterification reactions—with the natural ketoreductase activity inside yeast cell. The conformal silica bilayer provides protection while allowing proximity to catalytic sites and preserving natural cell viability and proliferation. These living nanobiohybrids offer to bridge cell’s natural biocatalytic capabilities with customizable heterogeneous metal catalysis, enabling programmable reaction sequences for sustainable chemical synthesis.
Differences in spatiotemporal brain network dynamics of Montessori and traditionally schooled students
Authors: Zanchi Paola , Mullier Emeline , Fornari Eleonora , Guerrier de Dumast Priscille , Alemán-Gómez Yasser , Ledoux Jean-Baptiste , Beaty Roger , Hagmann Patric , Denervaud Solange
Published: July 2024

Across development, experience has a strong impact on the way we think and adapt. School experience affects academic and social-emotional outcomes, yet whether differences in pedagogical experience modulate underlying brain network development is still unknown. In this study, we compared the brain network dynamics of students with different pedagogical backgrounds. Specifically, we characterized the diversity and stability of brain activity at rest by combining both resting-state fMRI and diffusion-weighted structural imaging data of 87 4–18 years old students experiencing either the Montessori pedagogy (i.e., student-led, trial-and-error pedagogy) or the traditional pedagogy (i.e., teacher-led, test-based pedagogy). Our results revealed spatiotemporal brain dynamics differences between students as a function of schooling experience at the whole-brain level. Students from Montessori schools showed overall higher functional integration (higher system diversity) and neural stability (lower spatiotemporal diversity) compared to traditionally schooled students. Higher integration was explained mainly through the cerebellar (CBL) functional network. In contrast, higher temporal stability was observed in the ventral attention, dorsal attention, somatomotor, frontoparietal, and CBL functional networks. This study suggests a form of experience-dependent dynamic functional connectivity plasticity, in learning-related networks.
Induced superconducting correlations in a quantum anomalous Hall insulator
Authors: Uday Anjana , Lippertz Gertjan , Moors Kristof , Legg Henry F. , Joris Rikkie , Bliesener Andrea , Pereira Lino M. C. , Taskin A. A. , Ando Yoichi
Published: July 2024

Thin films of ferromagnetic topological insulator materials can host the quantum anomalous Hall effect without the need for an external magnetic field. Inducing Cooper pairing in such a material is a promising way to realize topological superconductivity with the associated chiral Majorana edge states. However, finding evidence of the superconducting proximity effect in such a state has remained a considerable challenge due to inherent experimental difficulties. Here we demonstrate crossed Andreev reflection across a narrow superconducting Nb electrode that is in contact with the chiral edge state of a quantum anomalous Hall insulator. In the crossed Andreev reflection process, an electron injected from one terminal is reflected out as a hole at the other terminal to form a Cooper pair in the superconductor. This is a compelling signature of induced superconducting pair correlation in the chiral edge state. The characteristic length of the crossed Andreev reflection process is found to be much longer than the superconducting coherence length in Nb, which suggests that the crossed Andreev reflection is, indeed, mediated by superconductivity induced on the quantum anomalous Hall insulator surface. Our results will invite future studies of topological superconductivity and Majorana physics, as well as for the search for non-abelian zero modes.
In situ targeted base editing of bacteria in the mouse gut
Authors: Brödel Andreas K. , Charpenay Loïc H. , Galtier Matthieu , Fuche Fabien J. , Terrasse Rémi , Poquet Chloé , Havránek Jan , Pignotti Simone , Krawczyk Antonina , Arraou Marion , Prevot Gautier , Spadoni Dalila , Yarnall Matthew T. N. , Hessel Edith M. , Fernandez-Rodriguez Jesus , Duportet Xavier , Bikard David
Published: July 2024

Microbiome research is now demonstrating a growing number of bacterial strains and genes that affect our health1. Although CRISPR-derived tools have shown great success in editing disease-driving genes in human cells2, we currently lack the tools to achieve comparable success for bacterial targets in situ. Here we engineer a phage-derived particle to deliver a base editor and modify Escherichia coli colonizing the mouse gut. Editing of a β-lactamase gene in a model E. coli strain resulted in a median editing efficiency of 93% of the target bacterial population with a single dose. Edited bacteria were stably maintained in the mouse gut for at least 42 days following treatment. This was achieved using a non-replicative DNA vector, preventing maintenance and dissemination of the payload. We then leveraged this approach to edit several genes of therapeutic relevance in E. coli and Klebsiella pneumoniae strains in vitro and demonstrate in situ editing of a gene involved in the production of curli in a pathogenic E. coli strain. Our work demonstrates the feasibility of modifying bacteria directly in the gut, offering a new avenue to investigate the function of bacterial genes and opening the door to the design of new microbiome-targeted therapies.
Burden of gout among different WHO regions, 1990–2019: estimates from the global burden of disease study
Authors: Punjwani Shoheera , Jani Chinmay , Liu Weitao , Kakoullis Loukas , Salciccioli Ingrid , Al Omari Omar , Merchant Armaan , Singh Harpreet , Marshall Dominic , Shalhoub Joseph , Salciccioli Justin D. , Sehra Shiv T.
Published: July 2024

The global incidence of gout has increased rapidly, likely secondary to the increase in the prevalence of conditions that predispose to gout, such as obesity. Depending on the population studied, the prevalence of gout ranges from less than 1 to 6.8%. Thus, gout can be a significant burden on healthcare systems. The objective of this study is to observe the trends in the incidence, prevalence, and disability-adjusted life years (DALYs) of gout between 1990 and 2019 globally and in the European Union (EU) 15+ nations. We extracted data from the Global Burden of Disease Study database based on the International Classification of Diseases (ICD) versions 10 and 9. Incidence, prevalence, and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries and globally in males and females between 1990 and 2019. Joinpoint regression analysis was used to describe trends. Between 1990 and 2019, gout prevalence, incidence, and DALYs increased in both males (+ 21.42%, + 16.87%, + 21.49%, respectively) and females (+ 21.06%, + 18.75%, + 20.66%, respectively) globally. The United States of America had the highest increase in prevalence (males: + 90.6%; females + 47.1%), incidence (males: + 63.73%; females: + 39.11%) and DALYs (males: + 90.43%; females: + 42.75%). Incidence, prevalence, and DALYs from gout are increasing worldwide and in most of the EU15+ countries for males and females. Studies have reported the association of gout with comorbidities such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. Health policies and resource allocation are required to increase awareness and modify risk factors globally.
The impact of China's urbanization on ecosystem service value from the perspective of gross ecosystem product: a case study of Beijing-Tianjin-Hebei region
Authors: Fan Yu , Zheng Yun , Jia Changgeng , Song Youtao
Published: July 2024

Gross ecosystem product (GEP) is an aggregate measure of the monetary value of final ecosystem services, or the direct benefits that people derive from nature. GEP can provide decision makers with clear and competing evidence of the monetary value of ecosystem services. However, the relationship between GEP and urbanization has not been clarified which is not conducive to the decision-making role of GEP in the process of urban sustainable development. This work focused on the ‘Beijing-Tianjin-Hebei’ (BTH) urban agglomeration as a case study of the dynamics of ecological production amidst rapid economic and urban development, and coupled a spatial–temporal analysis of regional ecological change based on GIS (Geographic Information System) with economic valuation methods using official statistics and survey data. Results showed that from 2000 to 2020, the GEP increased from 1.55 trillion to 2.36 trillion, the value of provisioning services and cultural services increased from 0.51 to 0.71 trillion to 0.10–0.65 trillion. The value of regulation services showed an upward and downward trend (0.94–1.03–0.98) due to the rapid economic development in the Beijing-Tianjin-Hebei region. There were obvious spatial differences in the distribution of the GEP, in which Beijing, Tianjin, Tangshan, Cangzhou GEP accounted for 15%, 14%, 16% and 11%, respectively. During 2000–2020, there is a significant correlation between urbanization index (UI) and GEP in BTH, but the correlation between GEP and UI shows a trend of first increasing and then decreasing. The correlation between UI and EPS and ERS gradually decreases, and the impact of UI on ETS shows a significant positive correlation. In the future, it can be foreseen that urbanization will suppress the increase of GEP.
Gromov–Wasserstein unsupervised alignment reveals structural correspondences between the color similarity structures of humans and large language models
Authors: Kawakita Genji , Zeleznikow-Johnston Ariel , Tsuchiya Naotsugu , Oizumi Masafumi
Published: July 2024

Large Language Models (LLMs), such as the General Pre-trained Transformer (GPT), have shown remarkable performance in various cognitive tasks. However, it remains unclear whether these models have the ability to accurately infer human perceptual representations. Previous research has addressed this question by quantifying correlations between similarity response patterns of humans and LLMs. Correlation provides a measure of similarity, but it relies pre-defined item labels and does not distinguish category- and item- level similarity, falling short of characterizing detailed structural correspondence between humans and LLMs. To assess their structural equivalence in more detail, we propose the use of an unsupervised alignment method based on Gromov–Wasserstein optimal transport (GWOT). GWOT allows for the comparison of similarity structures without relying on pre-defined label correspondences and can reveal fine-grained structural similarities and differences that may not be detected by simple correlation analysis. Using a large dataset of similarity judgments of 93 colors, we compared the color similarity structures of humans (color-neurotypical and color-atypical participants) and two GPT models (GPT-3.5 and GPT-4). Our results show that the similarity structure of color-neurotypical participants can be remarkably well aligned with that of GPT-4 and, to a lesser extent, to that of GPT-3.5. These results contribute to the methodological advancements of comparing LLMs with human perception, and highlight the potential of unsupervised alignment methods to reveal detailed structural correspondences.
High contextual interference improves retention in motor learning: systematic review and meta-analysis
Authors: Czyż Stanisław H. , Wójcik Aleksandra M. , Solarská Petra , Kiper Paweł
Published: July 2024

The effect of practice schedule on retention and transfer has been studied since the first publication on contextual interference (CI) in 1966. However, strongly advocated by scientists and practitioners, the CI effect also aroused some doubts. Therefore, our objective was to review the existing literature on CI and to determine how it affects retention in motor learning. We found 1255 articles in the following databases: Scopus, EBSCO, Web of Science, PsycINFO, ScienceDirect, supplemented by the Google Scholar search engine. We screened full texts of 294 studies, of which 54 were included in the meta-analysis. In the meta-analyses, two different models were applied, i.e., a three-level mixed model and random-effects model with averaged effect sizes from single studies. According to both analyses, high CI has a medium beneficial effect on the whole population. These effects were statistically significant. We found that the random practice schedule in laboratory settings effectively improved motor skills retention. On the contrary, in the applied setting, the beneficial effect of random practice on the retention was almost negligible. The random schedule was more beneficial for retention in older adults (large effect size) and in adults (medium effect size). In young participants, the pooled effect size was negligible and statically insignificant.
Inferring the natural history of HPV from global cancer registries: insights from a multi-country calibration
Authors: Stuart Robyn M. , Cohen Jamie A. , Abeysuriya Romesh G. , Sanz-Leon Paula , Kerr Cliff C. , Rao Darcy , Klein Daniel J.
Published: July 2024

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV. Modeling can shed additional insight on the natural history of HPV, especially across geographical settings with varying prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were exactly identical for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV.
Formulation of silver phosphate/graphene/silica nanocomposite for enhancing the photocatalytic degradation of trypan blue dye in aqueous solution
Authors: Showman M. S. , Omara R. Y. , El-Ashtoukhy E-S. Z. , Farag H. A. , El-Latif M. M. Abd
Published: July 2024

Photocatalytic degradation of several harmful organic compounds has been presented as a potential approach to detoxify water in recent decades. Trypan Blue (TB) is an acidic azo dye used to distinguish live cells from dead ones and it's classified as a carcinogenic dye. In this study, silver phosphate (Ag3PO4) nanoparticles and novel Ag3PO4/graphene/SiO2 nanocomposite have been successfully prepared via simple precipitation method. Afterward, their physical properties, chemical composition, and morphology have been characterized using SEM, EDS, TEM, SAED, BET, XRD, FTIR and UV–VIS spectroscopy. The specific surface area of Ag3PO4 and Ag3PO4/G/SiO2 nanocomposite were reported to be 1.53 and 84.97 m2/g, respectively. The band gap energy of Ag3PO4 and Ag3PO4/G/SiO2 nanocomposite was measured to be 2.4 and 2.307 eV, respectively. Photocatalytic degradation of Trypan blue (TB) was studied at different parameters such as pH, catalyst dosage, initial concentration, and contact time. The results showed that, at initial dye concentration of 20 ppm, pH = 2, and using 0.03 g of Ag3PO4/G/SiO2 as a photocatalyst, the degradation percent of TB dye in the aqueous solution was 98.7% within 10 min of light exposure. Several adsorption isotherms such as Langmuir, Freundlich, and Temkin adsorption isotherms have been tested in addition to the photocatalytic degradation kinetics. Both catalysts were found to follow the Langmuir isotherm model and pseudo-second-order kinetic model. Finally, the possible photocatalytic performance mechanism of Ag3PO4/G/SiO2 was proposed.
Combined MediaPipe and YOLOv5 range of motion assessment system for spinal diseases and frozen shoulder
Authors: Zhang Weijia , Li Yulin , Cai Shaomin , Wang Zhaowei , Cheng Xue , Somjit Nutapong , Sun Dongqing , Chen Feiyu
Published: July 2024

Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.