bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the Onset Location of Equatorial Plasma Bubbles (EPBs) and Its Relationship With the Background Ionospheric Conditions
Authors: Ajith K. K. , Patra A. K. , Li Guozhu , Sripathi S. , Pavanchaitanya P. , Yamamoto M. , Perwitasari Septi
Published: April 2024

Using radars and C/NOFS satellite observations we studied the spatio‐temporal evolution of Equatorial Plasma Bubbles (EPBs) and estimated its onset location across a wide longitudinal sector over Indian and Southeast Asian longitudes. The vertical E × B drift velocity measurements obtained from the Ion Velocity Meter (IVM) on board the C/NOFS satellite and collocated ionosonde observations were used to examine the background ionospheric conditions. Our study shows that the periodic EPBs were present in those longitudes where periodic wave structure in the E × B drift and elevated F layer were observed. In this case study, the comprehensive analysis using the observations from radars and satellite data provides a better understanding on the longitudinal preference of the EPB occurrence and its responsible background mechanisms. This understanding of the onset location and background conditions of EPBs over a large longitudinal area for an extended period can contribute to the development of accurate EPB forecasting models, which are essential to mitigate the detrimental effects of EPBs on communication and navigation systems.
On the Spatio‐Temporal Scales of the Subtropical Mode Water Formation in the South Atlantic
Authors: Sato O. T. , Polito P. S. , Dottori M.
Published: April 2024

We examined the changes in the ocean’s upper layer structure involved in the formation of the subtropical mode water in the South Atlantic. Here we present the results from a survey done in the region of formation between 37°W and 32°W and 34°S and 37°S from July–October 2018, using high‐resolution measurements obtained from an underwater glider. From its records, the mode water development was observed for the first time in the South Atlantic as localized chimney‐like patterns in the temperature, salinity, and potential vorticity (PV) measurements with a horizontal scale of (7 ± 2) km, associated with wintertime oceanic convective processes. Over time, these submesoscale structures tend to expand and dominate the region as a large volume of mode water. These vertical structures present highly homogeneous temperature and salinity values. The observed PV was on the order of 5.0 × 10−11 m−1 s−1, which is one order of magnitude smaller than the pre‐existent mode water at the lower layers; negative values were observed, indicating active convection. A 1‐D vertical model was used to predict the depth of the mixed layer conditioned by the surface fluxes and triggered by its changes in winter to late spring. Comparisons of the sea surface temperature measured from satellite collocated with the glider’s measurements showed a very good agreement. From this analysis, we were able to establish the decorrelation scales that characterize mode water formation. Further inspection of the glider data yielded temporal decorrelation scales indicative of convection modified by planetary rotation.
Significance of Low‐Velocity Zones on Solute Retention in Rough Fractures
Authors: Sanglas Jordi , Trinchero Paolo , Painter Scott L. , Cvetkovic Vladimir , Poteri Antti , Selroos Jan‐Olof , Zou Liangchao
Published: April 2024

Natural fractures are characterized by high internal heterogeneity. This internal variability is the cause of flow channeling, which in turn leads to contaminant transport taking place primarily along the high‐velocity channels. Mass exchange between the high‐velocity channels and the low‐velocity zones has the potential to enhance contaminant retention, due to solute diffusion into the low‐velocity zones and subsequent exposure to additional surface area for diffusion into the bordering rock matrix. Here, we derive a random walk particle tracking method for heterogeneous fractures, which includes an additional term to account for the aperture gradient. The method takes into account advection, diffusion in the fracture and matrix diffusion. The developed numerical framework is applied to assess the effect of low‐velocity zones in rough self‐affine fractures. The results show that diffusion into low‐velocity zones has a visible but modest impact on contaminant retention. The magnitude of this impact does not change considerably, regardless of whether diffusion into the rock matrix is considered in the model, and increases for a decreasing average Péclet number of the fracture.
Noise annoyance due to different sources is associated with tinnitus presence and distress in the general population
Authors: Hahad Omar , Döge Julia , Bahr-Hamm Katharina , Beutel Manfred E. , Kontohow-Beckers Konstantin , Schuster Alexander K. , Keller Karsten , Hobohm Lukas , Schmitt Volker H. , Gianicolo Emilio , Lackner Karl J. , Daiber Andreas , Wild Philipp S. , Hackenberg Berit , Münzel Thomas
Published: April 2024

Background

The pathophysiology of tinnitus is not yet fully understood. Although there is a large amount of evidence associating traffic noise exposure with non-auditory health outcomes, there is no evidence regarding the impact of noise annoyance on auditory disorders such as tinnitus.

Objective

Thus, we aimed to investigate the association between noise annoyance due to different sources and tinnitus presence and distress in the general population.

Methods

Data of 6813 participants from a large German population-based cohort were used (Gutenberg Health Study). Participants were asked about the presence of tinnitus and how much they were bothered by it. In addition, information on annoyance from road traffic, aircraft, railways, industrial, and neighborhood noise during the day and sleep was collected through validated questionnaires.

Results

The prevalence of tinnitus was 27.3%, and the predominant sources of noise annoyance in these subjects were aircraft, neighborhood, and road traffic noise. Overall, logistic regression results demonstrated consistent positive associations between annoyance due to different noise sources and prevalent risk of tinnitus with increases in odds ratios ranging from 4 to 11% after adjustment for sex, age, and socioeconomic status. Likewise, consistent increases in odds ratios were observed for tinnitus distress in subjects with prevalent tinnitus. For instance, neighborhood noise annoyance during the sleep was associated with a 26% increase in tinnitus distress (OR 1.26, 95% CI 1.13; 1.39).

Impact

This is the first study investigating the association between noise annoyance and tinnitus presence and distress in a large cohort of the general population. Our results indicate consistent and positive associations between various sources of noise annoyance and tinnitus. These unprecedented findings are highly relevant as noise annoyance and tinnitus are widespread. The precise etiology and locus of tinnitus remain unknown, but excessive noise exposure is thought to be among the major causes. This study suggests that transportation and neighborhood noise levels thought merely to contribute to annoyance and non-auditory health effects may be sufficient to cause or exacerbate tinnitus.
Non-dipping blood pressure pattern is associated with cardiovascular events in a 21-year follow-up study
Authors: Lempiäinen Päivi A. , Ylitalo Antti , Huikuri Heikki , Kesäniemi Y. Antero , Ukkola Olavi H.
Published: April 2024

Non-dipping blood pressure (BP) pattern is a predictor for cardiovascular (CV) events and mortality. We evaluated dipping status change and its association with incidence of non-fatal CV events in middle-aged subjects. The OPERA study was carried out during the years 1991–1993, with a follow-up study 21.7 years later. In this study, we included 452 participants with 24-h ambulatory BP measurements (ABPM) available in both surveys. The study population was divided into four groups according to the dipping pattern change: dipping–dipping (n = 152/33.6%), dipping–non-dipping (n = 198/43.8%), non-dipping–dipping (n = 20/4.4%), and non-dipping–non-dipping (n = 82/18.1%). Sixty-five participants experienced a CV event (14.4%) during the 21.7 (SD 0.8) years of follow-up. The incidence of events was highest (28%) in the non-dipping–non-dipping group, and lowest (6.6%) in the dipping–dipping group (p < 0.001). In Cox regression analyses the covariates were age, sex, total cholesterol, hypertension and use of antihypertensive medication, systolic office BP and ambulatory mean or nighttime systolic BP, as well as the change in the variables during the follow-up period. After adjustments, the association of the non-dipping–non-dipping pattern with CV events compared with the dipping–dipping pattern remained significant (HR 4.01; 95% CI 1.89–8.67, p < 0.001). In summary, non-dipping–non-dipping pattern was associated with non-fatal CV events in the long term, and the effect was independent of the conventional risk factors including office and ambulatory BP levels.
Electron beams probe quantum coherence
Authors: Talebi Nahid
Published: April 2024

Scientists have traditionally employed superimposed mutually-coherent electron beams for holography and phase retrieval of electron wavepackets. However, recent theoretical exploration delves into the interaction of superposed electron beams with the matter. This investigation aims to elucidate long-range Coulomb correlations and quantum decoherence phenomena when electrons interact with their environment.
Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma
Authors: Jin Xing , Liu Lei , Liu Dan , Wu Jia , Wang Congcong , Wang Siliang , Wang Fengying , Yu Guanzhen , Jin Xiaoxia , Xue Yu-Wen , Jiang Dan , Ni Yan , Yang Xi , Wang Ming-Song , Wang Zhi-Wei , Orlov Yuriy L. , Jia Wei , Melino Gerry , Liu Ji-Bin , Chen Wen-Lian
Published: April 2024

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.
Enhancement of electrocatalysis through magnetic field effects on mass transport
Authors: Vensaus Priscila , Liang Yunchang , Ansermet Jean-Philippe , Soler-Illia Galo J. A. A. , Lingenfelder Magalí
Published: April 2024

Magnetic field effects on electrocatalysis have recently gained attention due to the substantial enhancement of the oxygen evolution reaction (OER) on ferromagnetic catalysts. When detecting an enhanced catalytic activity, the effect of magnetic fields on mass transport must be assessed. In this study, we employ a specifically designed magneto-electrochemical system and non-magnetic electrodes to quantify magnetic field effects. Our findings reveal a marginal enhancement in reactions with high reactant availability, such as the OER, whereas substantial boosts exceeding 50% are observed in diffusion limited reactions, exemplified by the oxygen reduction reaction (ORR). Direct visualization and quantification of the whirling motion of ions under a magnetic field underscore the importance of Lorentz forces acting on the electrolyte ions, and demonstrate that bubbles’ movement is a secondary phenomenon. Our results advance the fundamental understanding of magnetic fields in electrocatalysis and unveil new prospects for developing more efficient and sustainable energy conversion technologies.
Concomitant medication, comorbidity and survival in patients with breast cancer
Authors: Dumas Elise , Grandal Rejo Beatriz , Gougis Paul , Houzard Sophie , Abécassis Judith , Jochum Floriane , Marande Benjamin , Ballesta Annabelle , Del Nery Elaine , Dubois Thierry , Alsafadi Samar , Asselain Bernard , Latouche Aurélien , Espie Marc , Laas Enora , Coussy Florence , Bouchez Clémentine , Pierga Jean-Yves , Le Bihan-Benjamin Christine , Bousquet Philippe-Jean , Hotton Judicaël , Azencott Chloé-Agathe , Reyal Fabien , Hamy Anne-Sophie
Published: April 2024

Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform (https://adrenaline.curie.fr). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
Chemical unclonable functions based on operable random DNA pools
Authors: Luescher Anne M. , Gimpel Andreas L. , Stark Wendelin J. , Heckel Reinhard , Grass Robert N.
Published: April 2024

Physical unclonable functions (PUFs) based on unique tokens generated by random manufacturing processes have been proposed as an alternative to mathematical one-way algorithms. However, these tokens are not distributable, which is a disadvantage for decentralized applications. Finding unclonable, yet distributable functions would help bridge this gap and expand the applications of object-bound cryptography. Here we show that large random DNA pools with a segmented structure of alternating constant and randomly generated portions are able to calculate distinct outputs from millions of inputs in a specific and reproducible manner, in analogy to physical unclonable functions. Our experimental data with pools comprising up to >1010 unique sequences and encompassing >750 comparisons of resulting outputs demonstrate that the proposed chemical unclonable function (CUF) system is robust, distributable, and scalable. Based on this proof of concept, CUF-based anti-counterfeiting systems, non-fungible objects and decentralized multi-user authentication are conceivable.
Isotope engineering achieved by local coordination design in Ti-Pd co-doped ZrCo-based alloys
Authors: Qi Jiacheng , Huang Xu , Xiao Xuezhang , Zhang Xinyi , Zhou Panpan , Zhang Shuoqing , Li Ruhong , Kou Huaqin , Jiang Fei , Yao Yong , Song Jiangfeng , Feng Xingwen , Shi Yan , Luo Wenhua , Chen Lixin
Published: April 2024

Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in metal-hydrogen systems always disturbs precise D/T ratio control. Here, we reveal the dominance of kinetic isotope effect during desorption. To reconcile the thermodynamic stability and isotope effect, we demonstrate a quantitative indicator of Tgap and further a local coordination design strategy that comprises thermodynamic destabilization with vibration enhancement of interstitial isotopes for isotope engineering. Based on theoretical screening analysis, an optimized Ti-Pd co-doped Zr0.8Ti0.2Co0.8Pd0.2 alloy is designed and prepared. Compared to ZrCo alloy, the optimal alloy enables consistent isotope delivery together with a three-fold lower Tgap, a five-fold lower energy barrier difference, a one-third lower isotopic composition deviation during desorption and an over two-fold higher cycling capacity. This work provides insights into the interaction between alloy and hydrogen isotopes, thus opening up feasible approaches to support high-performance fusion reactors.
Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones
Authors: Denisenko Elena , de Kock Leanne , Tan Adeline , Beasley Aaron B. , Beilin Maria , Jones Matthew E. , Hou Rui , Muirí Dáithí Ó , Bilic Sanela , Mohan G. Raj K. A. , Salfinger Stuart , Fox Simon , Hmon Khaing P. W. , Yeow Yen , Kim Youngmi , John Rhea , Gilderman Tami S. , Killingbeck Emily , Gray Elin S. , Cohen Paul A. , Yu Yu , Forrest Alistair R. R.
Published: April 2024

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.
Nutrient-induced acidification modulates soil biodiversity-function relationships
Authors: Hu Zhengkun , Delgado-Baquerizo Manuel , Fanin Nicolas , Chen Xiaoyun , Zhou Yan , Du Guozhen , Hu Feng , Jiang Lin , Hu Shuijin , Liu Manqiang
Published: April 2024

Nutrient enrichment is a major global change component that often disrupts the relationship between aboveground biodiversity and ecosystem functions by promoting species dominance, altering trophic interactions, and reducing ecosystem stability. Emerging evidence indicates that nutrient enrichment also reduces soil biodiversity and weakens the relationship between belowground biodiversity and ecosystem functions, but the underlying mechanisms remain largely unclear. Here, we explore the effects of nutrient enrichment on soil properties, soil biodiversity, and multiple ecosystem functions through a 13-year field experiment. We show that soil acidification induced by nutrient enrichment, rather than changes in mineral nutrient and carbon (C) availability, is the primary factor negatively affecting the relationship between soil diversity and ecosystem multifunctionality. Nitrogen and phosphorus additions significantly reduce soil pH, diversity of bacteria, fungi and nematodes, as well as an array of ecosystem functions related to C and nutrient cycling. Effects of nutrient enrichment on microbial diversity also have negative consequences at higher trophic levels on the diversity of microbivorous nematodes. These results indicate that nutrient-induced acidification can cascade up its impacts along the soil food webs and influence ecosystem functioning, providing novel insight into the mechanisms through which nutrient enrichment influences soil community and ecosystem properties.
Hidden non-collinear spin-order induced topological surface states
Authors: Huang Zengle , Yi Hemian , Kaplan Daniel , Min Lujin , Tan Hengxin , Chan Ying-Ting , Mao Zhiqiang , Yan Binghai , Chang Cui-Zu , Wu Weida
Published: April 2024

Rare-earth monopnictides are a family of materials simultaneously displaying complex magnetism, strong electronic correlation, and topological band structure. The recently discovered emergent arc-like surface states in these materials have been attributed to the multi-wave-vector antiferromagnetic order, yet the direct experimental evidence has been elusive. Here we report observation of non-collinear antiferromagnetic order with multiple modulations using spin-polarized scanning tunneling microscopy. Moreover, we discover a hidden spin-rotation transition of single-to-multiple modulations 2 K below the Néel temperature. The hidden transition coincides with the onset of the surface states splitting observed by our angle-resolved photoemission spectroscopy measurements. Single modulation gives rise to a band inversion with induced topological surface states in a local momentum region while the full Brillouin zone carries trivial topological indices, and multiple modulation further splits the surface bands via non-collinear spin tilting, as revealed by our calculations. The direct evidence of the non-collinear spin order in NdSb not only clarifies the mechanism of the emergent topological surface states, but also opens up a new paradigm of control and manipulation of band topology with magnetism.
Ice shelf basal channel shape determines channelized ice-ocean interactions
Authors: Cheng Chen , Jenkins Adrian , Holland Paul R. , Wang Zhaomin , Dong Jihai , Liu Chengyan
Published: April 2024

Growing evidence has confirmed the critical role played by basal channels beneath Antarctic ice shelves in both ice shelf stability and freshwater input to the surrounding ocean. Here we show, using a 3D ice shelf-ocean boundary current model, that deeper basal channels can lead to a significant amplification in channelized basal melting, meltwater channeling, and warming and salinization of the channel flow. All of these channelized quantities are also modulated by channel width, with the level of modulation determined by channel height. The explicit quantification of channelized basal melting and the meltwater transport in terms of channel cross-sectional shape is potentially beneficial for the evaluation of ice shelf mass balance and meltwater contribution to the nearshore oceanography. Complicated topographically controlled circulations are revealed to be responsible for the unique thermohaline structure inside deep channels. Our study emphasizes the need for improvement in observations of evolving basal channels and the hydrography inside them, as well as adjacent to the ice front where channelized meltwater emerges.
Cryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment
Authors: Bharambe Nikhil , Li Zhuowen , Seiferth David , Balakrishna Asha Manikkoth , Biggin Philip C. , Basak Sandip
Published: April 2024

GLIC, a proton-activated prokaryotic ligand-gated ion channel, served as a model system for understanding the eukaryotic counterparts due to their structural and functional similarities. Despite extensive studies conducted on GLIC, the molecular mechanism of channel gating in the lipid environment requires further investigation. Here, we present the cryo-EM structures of nanodisc-reconstituted GLIC at neutral and acidic pH in the resolution range of 2.6 – 3.4 Å. In our apo state at pH 7.5, the extracellular domain (ECD) displays conformational variations compared to the existing apo structures. At pH 4.0, three distinct conformational states (C1, C2 and O states) are identified. The protonated structures exhibit a compacted and counter-clockwise rotated ECD compared with our apo state. A gradual widening of the pore in the TMD is observed upon reducing the pH, with the widest pore in O state, accompanied by several layers of water pentagons. The pore radius and molecular dynamics (MD) simulations suggest that the O state represents an open conductive state. We also observe state-dependent interactions between several lipids and proteins that may be involved in the regulation of channel gating. Our results provide comprehensive insights into the importance of lipids impact on gating.
Long lifetimes white afterglow in slightly crosslinked polymer systems
Authors: Chen Qingao , Qu Lunjun , Hou Hui , Huang Jiayue , Li Chen , Zhu Ying , Wang Yongkang , Chen Xiaohong , Zhou Qian , Yang Yan , Yang Chaolong
Published: April 2024

Intrinsic polymer room-temperature phosphorescence (IPRTP) materials have attracted considerable attention for application in flexible electronics, information encryption, lighting displays, and other fields due to their excellent processabilities and luminescence properties. However, achieving multicolor long-lived luminescence, particularly white afterglow, in undoped polymers is challenging. Herein, we propose a strategy of covalently coupling different conjugated chromophores with poly(acrylic acid (AA)-AA-N-succinimide ester) (PAA-NHS) by a simple and rapid one-pot reaction to obtain pure polymers with long-lived RTPs of various colors. Among these polymers, the highest phosphorescence quantum yield of PAPHE reaches 14.7%. Furthermore, the afterglow colors of polymers can be modulated from blue to red by introducing three chromophores into them. Importantly, the acquired polymer TPAP-514 exhibits a white afterglow at room temperature with the chromaticity coordinates (0.33, 0.33) when the ratio of chromophores reaches a suitable value owing to the three-primary-color mechanism. Systematic studies prove that the emission comes from the superposition of different triplet excited states of the three components. Moreover, the potential applications of the obtained polymers in light-emitting diodes and dynamic anti-counterfeiting are explored. The proposed strategy provides a new idea for constructing intrinsic polymers with diverse white-light emission RTPs.
Improving prime editing with an endogenous small RNA-binding protein
Authors: Yan Jun , Oyler-Castrillo Paul , Ravisankar Purnima , Ward Carl C. , Levesque Sébastien , Jing Yangwode , Simpson Danny , Zhao Anqi , Li Hui , Yan Weihao , Goudy Laine , Schmidt Ralf , Solley Sabrina C. , Gilbert Luke A. , Chan Michelle M. , Bauer Daniel E. , Marson Alexander , Parsons Lance R. , Adamson Britt
Published: April 2024

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3′ ends of CRISPR–Cas guide RNAs1. To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La. Further investigation revealed that La promotes prime editing across approaches (PE2, PE3, PE4 and PE5), edit types (substitutions, insertions and deletions), endogenous loci and cell types but has no consistent effect on genome-editing approaches that rely on standard, unextended guide RNAs. Previous work has shown that La binds polyuridine tracts at the 3′ ends of RNA polymerase III transcripts2. We found that La functionally interacts with the 3′ ends of polyuridylated prime editing guide RNAs (pegRNAs). Guided by these results, we developed a prime editor protein (PE7) fused to the RNA-binding, N-terminal domain of La. This editor improved prime editing with expressed pegRNAs and engineered pegRNAs (epegRNAs), as well as with synthetic pegRNAs optimized for La binding. Together, our results provide key insights into how prime editing components interact with the cellular environment and suggest general strategies for stabilizing exogenous small RNAs therein.
The variation and evolution of complete human centromeres
Authors: Logsdon Glennis A. , Rozanski Allison N. , Ryabov Fedor , Potapova Tamara , Shepelev Valery A. , Catacchio Claudia R. , Porubsky David , Mao Yafei , Yoo DongAhn , Rautiainen Mikko , Koren Sergey , Nurk Sergey , Lucas Julian K. , Hoekzema Kendra , Munson Katherine M. , Gerton Jennifer L. , Phillippy Adam M. , Ventura Mario , Alexandrov Ivan A. , Eichler Evan E.
Published: April 2024

Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.
A brain-specific angiogenic mechanism enabled by tip cell specialization
Authors: Schevenels Giel , Cabochette Pauline , America Michelle , Vandenborne Arnaud , De Grande Line , Guenther Stefan , He Liqun , Dieu Marc , Christou Basile , Vermeersch Marjorie , Germano Raoul F. V. , Perez-Morga David , Renard Patricia , Martin Maud , Vanlandewijck Michael , Betsholtz Christer , Vanhollebeke Benoit
Published: April 2024

Vertebrate organs require locally adapted blood vessels1,2. The gain of such organotypic vessel specializations is often deemed to be molecularly unrelated to the process of organ vascularization. Here, opposing this model, we reveal a molecular mechanism for brain-specific angiogenesis that operates under the control of Wnt7a/b ligands—well-known blood–brain barrier maturation signals3–5. The control mechanism relies on Wnt7a/b-dependent expression of Mmp25, which we find is enriched in brain endothelial cells. CRISPR–Cas9 mutagenesis in zebrafish reveals that this poorly characterized glycosylphosphatidylinositol-anchored matrix metalloproteinase is selectively required in endothelial tip cells to enable their initial migration across the pial basement membrane lining the brain surface. Mechanistically, Mmp25 confers brain invasive competence by cleaving meningeal fibroblast-derived collagen IV α5/6 chains within a short non-collagenous region of the central helical part of the heterotrimer. After genetic interference with the pial basement membrane composition, the Wnt–β-catenin-dependent organotypic control of brain angiogenesis is lost, resulting in properly patterned, yet blood–brain-barrier-defective cerebrovasculatures. We reveal an organ-specific angiogenesis mechanism, shed light on tip cell mechanistic angiodiversity and thereby illustrate how organs, by imposing local constraints on angiogenic tip cells, can select vessels matching their distinctive physiological requirements.
Optimizing PCF-SPR sensor design through Taguchi approach, machine learning, and genetic algorithms
Authors: Kaziz Sameh , Echouchene Fraj , Gazzah Mohamed Hichem
Published: April 2024

Designing Photonic Crystal Fibers incorporating the Surface Plasmon Resonance Phenomenon (PCF-SPR) has led to numerous interesting applications. This investigation presents an exceptionally responsive surface plasmon resonance sensor, seamlessly integrated into a dual-core photonic crystal fiber, specifically designed for low refractive index (RI) detection. The integration of a plasmonic material, namely silver (Ag), externally deposited on the fiber structure, facilitates real-time monitoring of variations in the refractive index of the surrounding medium. To ensure long-term functionality and prevent oxidation, a thin layer of titanium dioxide (TiO2) covers the silver coating. To optimize the sensor, five key design parameters, including pitch, air hole diameter, and silver thickness, are fine-tuned using the Taguchi L8(25) orthogonal array. The optimal results obtained present spectral and amplitude sensitivities that reach remarkable values of 10,000 nm/RIU and 235,882 RIU-1, respectively. In addition, Artificial Neural Network (ANN) optimization techniques, specifically Multi-Layer Perceptron (MLP) and Particle Swarm Optimization (PSO), are used to predict a critical optical property of the sensor confinement loss (αloss). These predictions are derived from the same input structure parameters that are present in the full L32(25) design experiment. A genetic algorithm (GA) is then applied for optimization with the goal of maximizing the confinement loss. Our results highlight the effectiveness of training PSO artificial neural networks and demonstrate their ability to quickly and accurately predict results for unknown geometric dimensions, demonstrating their significant potential in this innovative context. The proposed sensor design can be used for various applications including pharmaceutical inspection and detection of low refractive index analytes.
Gene expression plasticity facilitates acclimatization of a long-lived Caribbean coral across divergent reef environments
Authors: Castillo Karl D. , Bove Colleen B. , Hughes Annabel M. , Powell Maya E. , Ries Justin B. , Davies Sarah W.
Published: April 2024

Local adaptation can increase fitness under stable environmental conditions. However, in rapidly changing environments, compensatory mechanisms enabled through plasticity may better promote fitness. Climate change is causing devastating impacts on coral reefs globally and understanding the potential for adaptive and plastic responses is critical for reef management. We conducted a four-year, three-way reciprocal transplant of the Caribbean coral Siderastrea siderea across forereef, backreef, and nearshore populations in Belize to investigate the potential for environmental specialization versus plasticity in this species. Corals maintained high survival within forereef and backreef environments, but transplantation to nearshore environments resulted in high mortality, suggesting that nearshore environments present strong environmental selection. Only forereef-sourced corals demonstrated evidence of environmental specialization, exhibiting the highest growth in the forereef. Gene expression profiling 3.5 years post-transplantation revealed that transplanted coral hosts exhibited profiles more similar to other corals in the same reef environment, regardless of their source location, suggesting that transcriptome plasticity facilitates acclimatization to environmental change in S. siderea. In contrast, algal symbiont (Cladocopium goreaui) gene expression showcased functional variation between source locations that was maintained post-transplantation. Our findings suggest limited acclimatory capacity of some S. siderea populations under strong environmental selection and highlight the potential limits of coral physiological plasticity in reef restoration.
Exogenously applied gibberellic acid and benzylamine modulate growth and chemical constituents of dwarf schefflera: a stepwise regression analysis
Authors: Sardoei Ali Salehi , Tahmasebi Mojtaba , Bovand Fatemeh , Ghorbanpour Mansour
Published: April 2024

Ornamental foliage plants that have a dense appearance are highly valued. One way to achieve this is by using plant growth regulators as a tool for plant growth management. In a greenhouse with a mist irrigation system, a study was conducted on dwarf schefflera, an ornamental foliage plant, which was exposed to foliar application of gibberellic acid and benzyladenine hormones. The hormones were sprayed on dwarf schefflera leaves at 0, 100, and 200 mg/l concentrations, at 15-day intervals in three stages. The experiment was conducted as a factorial based on a completely randomized design, with four replicates. The combination of gibberellic acid and benzyladenine at 200 mg/l concentration had a significant effect on leaf number, leaf area, and plant height. The treatment also resulted in the highest content of photosynthetic pigments. Furthermore, the highest soluble carbohydrate to reducing sugars ratio was observed in treatments of 100 and 200 mg/l benzyladenine, and 200 mg/l gibberellic acid + benzyladenine. Stepwise regression analysis showed that root volume was the first variable to enter the model, explaining 44% of variations. The next variable was root fresh weight, and the two-variable model explained 63% of variations in leaf number. The greatest positive effect on leaf number was related to root fresh weight (0.43), which had a positive correlation with leaf number (0.47). The results showed that 200 mg/l concentration of gibberellic acid and benzyladenine significantly improved morphological growth, chlorophyll and carotenoid synthesis, and reducing sugar and soluble carbohydrate contents in dwarf schefflera.
Differentiation and functioning of the lateral line organ in zebrafish require Smpx activity
Authors: Diana Alberto , Ghilardi Anna , Del Giacco Luca
Published: April 2024

The small muscle protein, X-linked (SMPX) gene encodes a cytoskeleton-associated protein, highly expressed in the inner ear hair cells (HCs), possibly regulating auditory function. In the last decade, several mutations in SMPX have been associated with X-chromosomal progressive non syndromic hearing loss in humans and, in line with this, Smpx-deficient animal models, namely zebrafish and mouse, showed significant impairment of inner ear HCs development, maintenance, and functioning. In this work, we uncovered smpx expression in the neuromast mechanosensory HCs of both Anterior and Posterior Lateral Line (ALL and PLL, respectively) of zebrafish larvae and focused our attention on the PLL. Smpx was subcellularly localized throughout the cytoplasm of the HCs, as well as in their primary cilium. Loss-of-function experiments, via both morpholino-mediated gene knockdown and CRISPR/Cas9 F0 gene knockout, revealed that the lack of Smpx led to fewer properly differentiated and functional neuromasts, as well as to a smaller PLL primordium (PLLp), the latter also Smpx-positive. In addition, the kinocilia of Smpx-deficient neuromast HCs appeared structurally and numerically altered. Such phenotypes were associated with a significant reduction in the mechanotransduction activity of the neuromast HCs, in line with their positivity for Smpx. In summary, this work highlights the importance of Smpx in lateral line development and, specifically, in proper HCs differentiation and/or maintenance, and in the mechanotransduction process carried out by the neuromast HCs. Because lateral line HCs are both functionally and structurally analogous to the cochlear HCs, the neuromasts might represent an invaluable—and easily accessible—tool to dissect the role of Smpx in HCs development/functioning and shed light on the underlying mechanisms involved in hearing loss.
Increases in pre-stimulus theta and alpha oscillations precede successful encoding of crossmodal associations
Authors: Ostrowski Jan , Rose Michael
Published: April 2024

A central aspect of episodic memory is the formation of associations between stimuli from different modalities. Current theoretical approaches assume a functional role of ongoing oscillatory power and phase in the theta band (3–7 Hz) for the encoding of crossmodal associations. Furthermore, ongoing activity in the theta range as well as alpha (8–12 Hz) and low beta activity (13–20 Hz) before the presentation of a stimulus is thought to modulate subsequent cognitive processing, including processes that are related to memory. In this study, we tested the hypothesis that pre-stimulus characteristics of low frequency activity are relevant for the successful formation of crossmodal memory. The experimental design that was used specifically allowed for the investigation of associative memory independent from individual item memory. Participants (n = 51) were required to memorize associations between audiovisual stimulus pairs and distinguish them from newly arranged ones consisting of the same single stimuli in the subsequent recognition task. Our results show significant differences in the state of pre-stimulus theta and alpha power between remembered and not remembered crossmodal associations, clearly relating increased power to successful recognition. These differences were positively correlated with memory performance, suggesting functional relevance for behavioral measures of associative memory. Further analysis revealed similar effects in the low beta frequency ranges, indicating the involvement of different pre-stimulus-related cognitive processes. Phase-based connectivity measures in the theta band did not differ between remembered and not remembered stimulus pairs. The findings support the assumed functional relevance of theta band oscillations for the formation of associative memory and demonstrate that an increase of theta as well as alpha band oscillations in the pre-stimulus period is beneficial for the establishment of crossmodal memory.
Fairness and bias correction in machine learning for depression prediction across four study populations
Authors: Dang Vien Ngoc , Cascarano Anna , Mulder Rosa H. , Cecil Charlotte , Zuluaga Maria A. , Hernández-González Jerónimo , Lekadir Karim
Published: April 2024

A significant level of stigma and inequality exists in mental healthcare, especially in under-served populations. Inequalities are reflected in the data collected for scientific purposes. When not properly accounted for, machine learning (ML) models learned from data can reinforce these structural inequalities or biases. Here, we present a systematic study of bias in ML models designed to predict depression in four different case studies covering different countries and populations. We find that standard ML approaches regularly present biased behaviors. We also show that mitigation techniques, both standard and our own post-hoc method, can be effective in reducing the level of unfair bias. There is no one best ML model for depression prediction that provides equality of outcomes. This emphasizes the importance of analyzing fairness during model selection and transparent reporting about the impact of debiasing interventions. Finally, we also identify positive habits and open challenges that practitioners could follow to enhance fairness in their models.
National prevalence of smoking among adolescents at tobacco tax increase and COVID-19 pandemic in South Korea, 2005–2022
Authors: Hong Seohyun , Woo Selin , Kim Seokjun , Park Jaeyu , Lee Myeongcheol , Kim Sunyoung , Koyanagi Ai , Smith Lee , Kim Min Seo , López Sánchez Guillermo F. , Dragioti Elena , Rahmati Masoud , Fond Guillaume , Boyer Laurent , Oh Jiyeon , Lee Hojae , Yon Dong Keon
Published: April 2024

Prior research has predominantly focused on the overall effects of the tobacco tax increase and the COVID-19 pandemic on adolescent smoking behavior. However, there is a need to examine both the immediate and sustained associations of these two factors on subgroups of adolescents, employing an interrupted time-series model. We aimed to investigate the immediate and sustained association of tobacco tax increase and the COVID-19 pandemic on adolescent smoking prevalence. This study utilized data from the Korea Youth Risk Behavior Web-Based Survey to analyze the prevalence of current smoking among all participants (CSP) and the prevalence of daily smoking among current smokers (DSP) of Korean adolescents (n = 1,159,995; mean, age 14.99; male 51.5%) over 18 years from 2005 to 2022. The study examined 18-year trends in CSP and DSP among Korean adolescents, emphasizing the influences of the 2015 tobacco tax increase and the COVID-19 pandemic, using β coefficients and their differences (βdiff) from an interrupted time-series ARIMA model. While CSP exhibited a decreasing trend, DSP exhibited an increasing trend. Tobacco tax increase was associated with both the short and long terms in smoking prevalence, however, the short-term association on prevalence (CSP, − 3.076 [95% CI, − 3.707 to − 2.445]; DSP, − 4.112 [95% CI, − 6.488 to − 1.735]) was stronger. The pandemic was associated with an immediate increase in DSP (9.345 [95% CI, 5.285–13.406]). These effects were strongest among adolescents from low economic status and those exposed to familial secondhand smoking. Supportive programs for adolescents in low-income families will help overcome the effects associated with the pandemic. As a tobacco tax increase was associated with a reduction in smoking prevalence, this could be one method to overcome the effects of the pandemic.
Developer perspectives on the ethics of AI-driven neural implants: a qualitative study
Authors: van Stuijvenberg Odile C. , Broekman Marike L. D. , Wolff Samantha E. C. , Bredenoord Annelien L. , Jongsma Karin R.
Published: April 2024

Convergence of neural implants with artificial intelligence (AI) presents opportunities for the development of novel neural implants and improvement of existing neurotechnologies. While such technological innovation carries great promise for the restoration of neurological functions, they also raise ethical challenges. Developers of AI-driven neural implants possess valuable knowledge on the possibilities, limitations and challenges raised by these innovations; yet their perspectives are underrepresented in academic literature. This study aims to explore perspectives of developers of neurotechnology to outline ethical implications of three AI-driven neural implants: a cochlear implant, a visual neural implant, and a motor intention decoding speech-brain-computer-interface. We conducted semi-structured focus groups with developers (n = 19) of AI-driven neural implants. Respondents shared ethically relevant considerations about AI-driven neural implants that we clustered into three themes: (1) design aspects; (2) challenges in clinical trials; (3) impact on users and society. Developers considered accuracy and reliability of AI-driven neural implants conditional for users’ safety, authenticity, and mental privacy. These needs were magnified by the convergence with AI. Yet, the need for accuracy and reliability may also conflict with potential benefits of AI in terms of efficiency and complex data interpretation. We discuss strategies to mitigate these challenges.