bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light People: Prof. Eric Mazur speaks about ultrafast optics and education
Authors: Guo Chenzi , Li Yang 
Published: February 2024

EditorialProf. Eric Mazur is a great influencer over and beyond the optics community. As a physicist, he is a pioneer of ultrafast optics and was one of the inventors of colliding-pulse mode-locked laser. As an educator, he not only gave talks to thousands, but also revolutionized teaching with his globally renowned methodology “Peer Instruction”. As a leader and entrepreneur, he co-founded several companies and was President of Optica (formerly the Optical Society) and currently is the Chair of the Optica Foundation. Here, Light: Science & Applications talked with Prof. Eric Mazur about his opinions on research, education and industry. The full interview video can be found in the Supplementary File.
Aging impairs the osteocytic regulation of collagen integrity and bone quality
Authors: Schurman Charles A. , Kaya Serra , Dole Neha , Luna Nadja M. Maldonado , Castillo Natalia , Potter Ryan , Rose Jacob P. , Bons Joanna , King Christina D. , Burton Jordan B. , Schilling Birgit , Melov Simon , Tang Simon , Schaible Eric , Alliston Tamara 
Published: February 2024

AbstractPoor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRIIocy−/−) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRIIocy−/− bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.
Concurrent inhibition of pBADS99 synergistically improves MEK inhibitor efficacy in KRASG12D-mutant pancreatic ductal adenocarcinoma
Authors: Tan Yan Qin , Sun Bowen , Zhang Xi , Zhang Shuwei , Guo Hui , Basappa Basappa , Zhu Tao , Sethi Gautam , Lobie Peter E. , Pandey Vijay 
Published: February 2024

AbstractTherapeutic targeting of KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) has remained a significant challenge in clinical oncology. Direct targeting of KRAS has proven difficult, and inhibition of the KRAS effectors have shown limited success due to compensatory activation of survival pathways. Being a core downstream effector of the KRAS-driven p44/42 MAPK and PI3K/AKT pathways governing intrinsic apoptosis, BAD phosphorylation emerges as a promising therapeutic target. Herein, a positive association of the pBADS99/BAD ratio with higher disease stage and worse overall survival of PDAC was observed. Homology-directed repair of BAD to BADS99A or small molecule inhibition of BADS99 phosphorylation by NCK significantly reduced PDAC cell viability by promoting cell cycle arrest and apoptosis. NCK also abrogated the growth of preformed colonies of PDAC cells in 3D culture. Furthermore, high-throughput screening with an oncology drug library to identify potential combinations revealed a strong synergistic effect between NCK and MEK inhibitors in PDAC cells harboring either wild-type or mutant-KRAS. Mechanistically, both mutant-KRAS and MEK inhibition increased the phosphorylation of BADS99 in PDAC cells, an effect abrogated by NCK. Combined pBADS99-MEK inhibition demonstrated strong synergy in reducing cell viability, enhancing apoptosis, and achieving xenograft stasis in KRAS-mutant PDAC. In conclusion, the inhibition of BADS99 phosphorylation enhances the efficacy of MEK inhibition, and their combined inhibition represents a mechanistically based and potentially effective therapeutic strategy for the treatment of KRAS-mutant PDAC.
The regulated cell death at the maternal-fetal interface: beneficial or detrimental?
Authors: Chen Huan , Chen Yin , Zheng Qingliang 
Published: February 2024

AbstractRegulated cell death (RCD) plays a fundamental role in placental development and tissue homeostasis. Placental development relies upon effective implantation and invasion of the maternal decidua by the trophoblast and an immune tolerant environment maintained by various cells at the maternal-fetal interface. Although cell death in the placenta can affect fetal development and even cause pregnancy-related diseases, accumulating evidence has revealed that several regulated cell death were found at the maternal-fetal interface under physiological or pathological conditions, the exact types of cell death and the precise molecular mechanisms remain elusive. In this review, we summarized the apoptosis, necroptosis and autophagy play both promoting and inhibiting roles in the differentiation, invasion of trophoblast, remodeling of the uterine spiral artery and decidualization, whereas ferroptosis and pyroptosis have adverse effects. RCD serves as a mode of communication between different cells to better maintain the maternal-fetal interface microenvironment. Maintaining the balance of RCD at the maternal-fetal interface is of utmost importance for the development of the placenta, establishment of an immune microenvironment, and prevention of pregnancy disorders. In addition, we also revealed an association between abnormal expression of key molecules in different types of RCD and pregnancy-related diseases, which may yield significant insights into the pathogenesis and treatment of pregnancy-related complications.
In situ copper faceting enables efficient CO2/CO electrolysis
Authors: Yao Kaili , Li Jun , Ozden Adnan , Wang Haibin , Sun Ning , Liu Pengyu , Zhong Wen , Zhou Wei , Zhou Jieshu , Wang Xi , Liu Hanqi , Liu Yongchang , Chen Songhua , Hu Yongfeng , Wang Ziyun , Sinton David , Liang Hongyan 
Published: February 2024

AbstractThe copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm−2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm−2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout.
Energy transfer driven brightening of MoS2 by ultrafast polariton relaxation in microcavity MoS2/hBN/WS2 heterostructures
Authors: Hu Zehua , Krisnanda Tanjung , Fieramosca Antonio , Zhao Jiaxin , Sun Qianlu , Chen Yuzhong , Liu Haiyun , Luo Yuan , Su Rui , Wang Junyong , Watanabe Kenji , Taniguchi Takashi , Eda Goki , Wang Xiao Renshaw , Ghosh Sanjib , Dini Kevin , Sanvitto Daniele , Liew Timothy C. H. , Xiong Qihua 
Published: February 2024

AbstractEnergy transfer is a ubiquitous phenomenon that delivers energy from a blue-shifted emitter to a red-shifted absorber, facilitating wide photonic applications. Two-dimensional (2D) semiconductors provide unique opportunities for exploring novel energy transfer mechanisms in the atomic-scale limit. Herein, we have designed a planar optical microcavity-confined MoS2/hBN/WS2 heterojunction, which realizes the strong coupling among donor exciton, acceptor exciton, and cavity photon mode. This configuration demonstrates an unconventional energy transfer via polariton relaxation, brightening MoS2 with a record-high enhancement factor of ~440, i.e., two-order-of-magnitude higher than the data reported to date. The polariton relaxation features a short characteristic time of ~1.3 ps, resulting from the significantly enhanced intra- and inter-branch exciton-exciton scattering. The polariton relaxation dynamics is associated with Rabi energies in a phase diagram by combining experimental and theoretical results. This study opens a new direction of microcavity 2D semiconductor heterojunctions for high-brightness polaritonic light sources and ultrafast polariton carrier dynamics.
High-strength and crack-free welding of 2024 aluminium alloy via Zr-core-Al-shell wire
Authors: Jin Jun , Geng Shaoning , Shu Leshi , Jiang Ping , Shao Xinyu , Han Chu , Ren Liangyuan , Li Yuantai , Yang Lu , Wang Xiangqi 
Published: February 2024

AbstractThe 2000 series aluminium alloys are qualified for widespread use in lightweight structures, but solidification cracking during fusion welding has been a long-standing issue. Here, we create a zirconium (Zr)-core-aluminium (Al)-shell wire (ZCASW) and employ the oscillating laser-arc hybrid welding technique to control solidification during welding, and ultimately achieve reliable and crack-free welding of 2024 aluminium alloy. We select Zr wires with an ideal lattice match to Al based on crystallographic information and wind them by the Al wires with similar chemical components to the parent material. Crack-free, equiaxed (where the length, width and height of the grains are roughly equal), fine-grained microstructures are acquired, thereby considerably increasing the tensile strength over that of conventional fusion welding joints, and even comparable to that of friction stir welding joints. This work has important engineering application value in welding of high-strength aluminum alloys.
Femtosecond electron beam probe of ultrafast electronics
Authors: Mattes Maximilian , Volkov Mikhail , Baum Peter 
Published: February 2024

AbstractThe need for ever-faster information processing requires exceptionally small devices that operate at frequencies approaching the terahertz and petahertz regimes. For the diagnostics of such devices, researchers need a spatiotemporal tool that surpasses the device under test in speed and spatial resolution. Consequently, such a tool cannot be provided by electronics itself. Here we show how ultrafast electron beam probe with terahertz-compressed electron pulses can directly sense local electro-magnetic fields in electronic devices with femtosecond, micrometre and millivolt resolution under normal operation conditions. We analyse the dynamical response of a coplanar waveguide circuit and reveal the impulse response, signal reflections, attenuation and waveguide dispersion directly in the time domain. The demonstrated measurement bandwidth reaches 10 THz and the sensitivity to electric potentials is tens of millivolts or −20 dBm. Femtosecond time resolution and the capability to directly integrate our technique into existing electron-beam inspection devices in semiconductor industry makes our femtosecond electron beam probe a promising tool for research and development of next-generation electronics at unprecedented speed and size.
Engineering self-deliverable ribonucleoproteins for genome editing in the brain
Authors: Chen Kai , Stahl Elizabeth C. , Kang Min Hyung , Xu Bryant , Allen Ryan , Trinidad Marena , Doudna Jennifer A. 
Published: February 2024

AbstractThe delivery of CRISPR ribonucleoproteins (RNPs) for genome editing in vitro and in vivo has important advantages over other delivery methods, including reduced off-target and immunogenic effects. However, effective delivery of RNPs remains challenging in certain cell types due to low efficiency and cell toxicity. To address these issues, we engineer self-deliverable RNPs that can promote efficient cellular uptake and carry out robust genome editing without the need for helper materials or biomolecules. Screening of cell-penetrating peptides (CPPs) fused to CRISPR-Cas9 protein identifies potent constructs capable of efficient genome editing of neural progenitor cells. Further engineering of these fusion proteins establishes a C-terminal Cas9 fusion with three copies of A22p, a peptide derived from human semaphorin-3a, that exhibits substantially improved editing efficacy compared to other constructs. We find that self-deliverable Cas9 RNPs generate robust genome edits in clinically relevant genes when injected directly into the mouse striatum. Overall, self-deliverable Cas9 proteins provide a facile and effective platform for genome editing in vitro and in vivo.
Monitoring the mass, eigenfrequency, and quality factor of mammalian cells
Authors: Herzog Sophie , Fläschner Gotthold , Incaviglia Ilaria , Arias Javier Casares , Ponti Aaron , Strohmeyer Nico , Nava Michele M. , Müller Daniel J. 
Published: February 2024

AbstractThe regulation of mass is essential for the development and homeostasis of cells and multicellular organisms. However, cell mass is also tightly linked to cell mechanical properties, which depend on the time scales at which they are measured and change drastically at the cellular eigenfrequency. So far, it has not been possible to determine cell mass and eigenfrequency together. Here, we introduce microcantilevers oscillating in the Ångström range to monitor both fundamental physical properties of the cell. If the oscillation frequency is far below the cellular eigenfrequency, all cell compartments follow the cantilever motion, and the cell mass measurements are accurate. Yet, if the oscillating frequency approaches or lies above the cellular eigenfrequency, the mechanical response of the cell changes, and not all cellular components can follow the cantilever motions in phase. This energy loss caused by mechanical damping within the cell is described by the quality factor. We use these observations to examine living cells across externally applied mechanical frequency ranges and to measure their total mass, eigenfrequency, and quality factor. The three parameters open the door to better understand the mechanobiology of the cell and stimulate biotechnological and medical innovations.
Interplay between coding and non-coding regulation drives the Arabidopsis seed-to-seedling transition
Authors: Tremblay Benjamin J. M. , Santini Cristina P. , Cheng Yajiao , Zhang Xue , Rosa Stefanie , Qüesta Julia I. 
Published: February 2024

AbstractTranslation of seed stored mRNAs is essential to trigger germination. However, when RNAPII re-engages RNA synthesis during the seed-to-seedling transition has remained in question. Combining csRNA-seq, ATAC-seq and smFISH in Arabidopsis thaliana we demonstrate that active transcription initiation is detectable during the entire germination process. Features of non-coding regulation such as dynamic changes in chromatin accessible regions, antisense transcription, as well as bidirectional non-coding promoters are widespread throughout the Arabidopsis genome. We show that sensitivity to exogenous ABSCISIC ACID (ABA) during germination depends on proximal promoter accessibility at ABA-responsive genes. Moreover, we provide genetic validation of the existence of divergent transcription in plants. Our results reveal that active enhancer elements are transcribed producing non-coding enhancer RNAs (eRNAs) as widely documented in metazoans. In sum, this study defining the extent and role of coding and non-coding transcription during key stages of germination expands our understanding of transcriptional mechanisms underlying plant developmental transitions.
SEMORE: SEgmentation and MORphological fingErprinting by machine learning automates super-resolution data analysis
Authors: Bender Steen W. B. , Dreisler Marcus W. , Zhang Min , Kæstel-Hansen Jacob , Hatzakis Nikos S. 
Published: February 2024

AbstractThe morphology of protein assemblies impacts their behaviour and contributes to beneficial and aberrant cellular responses. While single-molecule localization microscopy provides the required spatial resolution to investigate these assemblies, the lack of universal robust analytical tools to extract and quantify underlying structures limits this powerful technique. Here we present SEMORE, a semi-automatic machine learning framework for universal, system- and input-dependent, analysis of super-resolution data. SEMORE implements a multi-layered density-based clustering module to dissect biological assemblies and a morphology fingerprinting module for quantification by multiple geometric and kinetics-based descriptors. We demonstrate SEMORE on simulations and diverse raw super-resolution data: time-resolved insulin aggregates, and published data of dSTORM imaging of nuclear pore complexes, fibroblast growth receptor 1, sptPALM of Syntaxin 1a and dynamic live-cell PALM of ryanodine receptors. SEMORE extracts and quantifies all protein assemblies, their temporal morphology evolution and provides quantitative insights, e.g. classification of heterogeneous insulin aggregation pathways and NPC geometry in minutes. SEMORE is a general analysis platform for super-resolution data, and being a time-aware framework can also support the rise of 4D super-resolution data.
S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens
Authors: Jia Mutian , Chai Li , Wang Jie , Wang Mengge , Qin Danhui , Song Hui , Fu Yue , Zhao Chunyuan , Gao Chengjiang , Jia Jihui , Zhao Wei 
Published: February 2024

AbstractOxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis.
DNA and RNA base editors can correct the majority of pathogenic single nucleotide variants
Authors: Dadush Ariel , Merdler-Rabinowicz Rona , Gorelik David , Feiglin Ariel , Buchumenski Ilana , Pal Lipika R. , Ben-Aroya Shay , Ruppin Eytan , Levanon Erez Y. 
Published: February 2024

AbstractThe majority of human genetic diseases are caused by single nucleotide variants (SNVs) in the genome sequence. Excitingly, new genomic techniques known as base editing have opened efficient pathways to correct erroneous nucleotides. Due to reliance on deaminases, which have the capability to convert A to I(G) and C to U, the direct applicability of base editing might seem constrained in terms of the range of mutations that can be reverted. In this evaluation, we assess the potential of DNA and RNA base editing methods for treating human genetic diseases. Our findings indicate that 62% of pathogenic SNVs found within genes can be amended by base editing; 30% are G>A and T>C SNVs that can be corrected by DNA base editing, and most of them by RNA base editing as well, and 29% are C>T and A>G SNVs that can be corrected by DNA base editing directed to the complementary strand. For each, we also present several factors that affect applicability such as bystander and off-target occurrences. For cases where editing the mismatched nucleotide is not feasible, we introduce an approach that calculates the optimal substitution of the deleterious amino acid with a new amino acid, further expanding the scope of applicability. As personalized therapy is rapidly advancing, our demonstration that most SNVs can be treated by base editing is of high importance. The data provided will serve as a comprehensive resource for those seeking to design therapeutic base editors and study their potential in curing genetic diseases.
Frequency-specific and periodic masking of peripheral characters by delayed foveal input
Authors: Goktepe Nedim , Schütz Alexander C. 
Published: February 2024

AbstractThe foveal-feedback mechanism supports peripheral object recognition by processing information about peripheral objects in foveal retinotopic visual cortex. When a foveal object is asynchronously presented with a peripheral target, peripheral discrimination performance is affected differently depending on the relationship between the foveal and peripheral objects. However, it is not clear whether the delayed foveal input competes for foveal resources with the information processed by foveal-feedback or masks it. In the current study, we tested these hypotheses by measuring the effect of foveal noise at different spatial frequencies on peripheral discrimination of familiar and novel characters. Our results showed that the impairment of foveal-feedback was strongest for low-spatial frequency noise. A control experiment revealed that for spatially overlapping noise, low-spatial frequencies were more effective than medium-spatial frequencies in the periphery, but vice versa in the fovea. This suggests that the delayed foveal input selectively masks foveal-feedback when it is sufficiently similar to the peripheral information. Additionally, this foveal masking was periodic as evidenced by behavioral oscillations at around 5 Hz. Thus, we conclude that foveal-feedback supports peripheral discrimination of familiar and novel objects by periodically processing peripheral object information.