bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions
Authors: Zhong Yan , Liu Jingfeng 
Published: July 2024

AbstractCancer 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

AbstractDepression 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

AbstractVisual 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

AbstractNext-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

AbstractCompetence 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

AbstractNatural 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

AbstractComputational 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

AbstractHydrogenation 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

AbstractThe 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

AbstractLong-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

AbstractThe 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

AbstractSelf-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

AbstractTo 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

AbstractPlasmodium 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

AbstractControlling 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.