bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic assessment of the causal effect of plasma metabolites and metabolic pathways on delirium
Authors: He Xin , Shi XinYu , Wang YiNi , Han Shuang , Liu JiaYan , Yang Fei , Ma Kun , Li Bai-Xiang 
Published: August 2024

Abstract
Purpose
Delirium has a significant impact on millions of people globally and is closely linked to an unfavorable prognosis for complications. Observational studies suggest that plasma metabolites may play significant roles as markers and effectors of delirium, but causal relationships have not yet been elucidated. Based on the most recent genome-wide association study (GWAS) data, our study aims to present novel insights into the genetic relationship between delirium and plasma metabolites. This investigation offers potential clues for utilizing plasma metabolites as predictors of delirium development.

Methods
We performed a thorough Mendelian randomization (MR) analysis to investigate the causal relationship between 1,091 individual metabolites and 309 metabolite ratios in plasma with respect to delirium. Inverse-variance weighting (IVW) was employed as the primary estimation method, while MR-Egger and weighed median methods were utilized to assess the robustness of the results. Sensitivity analyses encompassing the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, Cochran Q test, leave-one-out analysis and MR Egger intercept analysis were also undertaken. Additionally, the MR Steiger test was performed to explore any potential reverse causal effect of metabolites on delirium.

Results
A total of 63 types of plasma metabolites associated with delirium were detected using the IVW method (p < 0.05). Among the known metabolites, our analysis revealed that two specific metabolites (1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and homovanillate) and a metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) demonstrated a consistent and significant causal relationship with delirium across all analysis methods. Finally, no evidence of pleiotropy was detected in our analysis.

Conclusions
Our study has revealed a causal association between blood metabolites and the risk of delirium. homovanillate is known to be associated with immunity and redox, 1-palmitoyl-2-palmitoleoyl-gpc (16:0/16:1) and metabolite ratio (phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2)) may play a role in lipid regulation. These findings may provide fresh insights into the identification of suitable diagnostic markers and potential treatment strategies focused on specific plasma metabolites in patients with delirium. However, further experiments are required to gain a comprehensive understanding of the underlying biological mechanisms involved.
Quantifying the Mean Sea Level, Tide, and Surge Contributions to Changing Coastal High Water Levels
Authors: Palmer Karen , Watson Christopher S. , Power Hannah E. , Hunter John R. 
Published: August 2024

AbstractThe likelihood of coastal inundation (high tide flooding) depends on the coincidence of mean sea level (MSL), high tide, and surge, relative to the height of local thresholds. Here we present a nonparametric Joint Probability of Maxima Method for deriving frequency‐based exceedance thresholds and for quantifying the changing heights of water level maxima. Our approach builds upon the Skew Surge Joint Probability Method (Batstone et al., 2013, https://doi.org/10.1016/j.oceaneng.2013.02.003) in using predicted high water (HW) level and skew surge components, adding MSL as a third component, and accounting for seasonal variation. From the derived distributions, we obtain threshold levels exceeded at specific average recurrence intervals of 1, 5, and 10 years. Changes in exceedances are compared between two 19‐year epochs for 166 tide gauges: 140 from a global data set (GESLA: 1983–2001 vs. 2002–2020), and 26 from an Australian data set (BoM: 1992–2010 vs. 2004–2022). We find that the change in exceedance levels between epochs typically exceeds the respective change in MSL and varies between the different threshold levels. We quantify the specific contribution of each component, finding that MSL contributions are influential at most sites, while tides contribute a lesser amount, and surge contributions vary substantially. Exceedance frequency more than doubles on average and increases most at those locations with the smallest variability in the height of high tide. Our approach serves to address a critical gap in offering specific and localized measures of changes in coastal inundation frequency.
Influence of the Remote Equatorial Dynamics on the Interannual Variability Along the Northern Coast of the Gulf of Guinea
Authors: Illig Serena , Djakouré Sandrine , Mitchodigni Toussaint 
Published: August 2024

AbstractThis study explores the oceanic connection between the equatorial dynamics and the coastal variability along the northern coast of the Gulf of Guinea on interannual timescales, based on experiments with a high‐resolution tropical Atlantic Ocean model over 1958–2015. Equatorial Kelvin waves, forced by wind‐stress anomalies in the west‐central equatorial basin, significantly control the interannual fluctuations of the coastal sea‐level and subsurface temperature near the thermocline (>70%), leaving only a marginal role for the local forcing contribution. The dynamical coastal response exhibits a clear propagative nature, with poleward propagations (0.75–1.2 m.s−1) from Cameroon to Liberia. Because the northern coast of the Gulf of Guinea is close to the equatorial waveguide, the coastal variability is influenced by both equatorially‐forced coastal trapped waves and reflected equatorial Rossby waves. Furthermore, remote equatorial forcing explains more of the surface temperature variance for the coastal systems associated with clear upwelling characteristics such as Côte d'Ivoire and Ghana, where subsurface/surface coupling is more efficient. The surface thermal amplitude and timing is shaped by the coastal stratification and circulation and exhibits a marked seasonal modulation, so that the timing of the Sea Surface Temperature (SST) anomalies relative to the dynamical signature lacks consistency, making SST a less reliable variable for tracking coastal propagations in the Gulf of Guinea. Our findings open the possibility of predicting interannual changes in coastal conditions off Côte d'Ivoire and Ghana a few months in advance, to anticipate impacts on fish habitats and resources, and to facilitate proactive measures for sustainable management and conservation efforts.
Physical Drivers of Surface Water Retention in the Santa Barbara Channel
Authors: Brokaw R. J. , Siegel D. A. , Washburn L. 
Published: August 2024

AbstractRetention of surface water parcels can benefit coastal ecosystems by increasing the residence times of nutrient‐rich waters and marine larvae but can also negatively impact marine life and human health by concentrating oil and other pollutants. To investigate the spatial patterns, temporal variability, and drivers of retention, surface water parcel retention is quantified using particle simulations forced by high‐frequency radar surface current observations in the Santa Barbara Channel (SBC), California, USA. Retention is defined here as the time a particle remains within 20 km of its starting location and typical retention times are ∼4 days. However, the mechanisms driving retention differ across the SBC. In the central SBC, high retention times are driven by a persistent cyclonic eddy, while in the eastern SBC, high retention times are due to weak oscillatory flow. Areas in the western SBC outside of the cyclonic eddy exhibit the shortest mean retention times (<2 days) due to sustained horizontal advection. Stepwise regression is used to assess the drivers of interannual retention anomalies at sub‐SBC scales and is able to predict the greatest (least) amount of retention variability in the western (eastern) SBC. The presence of coherent eddies, both cyclonic and anticyclonic, is a dominant driver of high retention channel‐wide, while some factors such as wind stress and along‐channel flow have counteracting effects on retention at sub‐channel scales.
UPF3B modulates endoplasmic reticulum stress through interaction with inositol-requiring enzyme-1α
Authors: Sun XingSheng , Lin Ruqin , Lu Xinxia , Wu Zhikai , Qi Xueying , Jiang Tianqing , Jiang Jun , Mu Peiqiang , Chen Qingmei , Wen Jikai , Deng Yiqun 
Published: August 2024

AbstractThe unfolded protein response (UPR) is a conserved and adaptive intracellular pathway that relieves the endoplasmic reticulum (ER) stress by activating ER transmembrane stress sensors. As a consequence of ER stress, the inhibition of nonsense-mediated mRNA decay (NMD) is due to an increase in the phosphorylation of eIF2α, which has the effect of inhibiting translation. However, the role of NMD in maintaining ER homeostasis remains unclear. In this study, we found that the three NMD factors, up-frameshift (UPF)1, UPF2, or UPF3B, were required to negate the UPR. Among these three NMD factors, only UPF3B interacted with inositol-requiring enzyme-1α (IRE1α). This interaction inhibited the kinase activity of IRE1α, abolished autophosphorylation, and reduced IRE1α clustering for ER stress. BiP and UPF3B jointly control the activation of IRE1α on both sides of the ER membrane. Under stress conditions, the phosphorylation of UPF3B was increased and the phosphorylated sites were identified. Both the UPF3BY160D genetic mutation and phosphorylation at Thr169 of UPF3B abolished its interaction with IRE1α and UPF2, respectively, leading to activation of ER stress and NMD dysfunction. Our study reveals a key physiological role for UPF3B in the reciprocal regulatory relationship between NMD and ER stress.
Postprandial hypotension is more common than orthostatic hypotension in older adults with dementia with lewy bodies: a cross-sectional study
Authors: Isik Ahmet Turan , Ontan Mehmet Selman , Dost Fatma Sena , Mutlay Feyza , Cam Mahser Alev , Gokdeniz Yildirim Acelya , Kaya Derya 
Published: August 2024

AbstractCardiovascular autonomic dysfunction is one of the supportive clinical features in dementia with Lewy bodies (DLB). This study aimed to investigate the frequency of postural and postprandial hypotension in people with DLB. The study group comprised 125 patients with DLB (76 females; mean age 78.4 ± 7.1 years) and 122 controls (88 females; mean age 74.4 ± 6.9 years). Postprandial blood pressure changes were assessed by ambulatory 24-hour blood pressure monitorization. Postural blood pressure changes were assessed via the head-up tilt table test. The frequency of postprandial hypotension (PPH) and orthostatic hypotension (OH) was higher in patients with DLB compared to controls (89.4% vs 51.7%; p < 0.001, and 45.5% vs 27.9%; p = 0.004, respectively) whereas the frequency of supine hypertension (SH), and orthostatic hypertension (OHT) was similar. However, SH in non-hypertensive participants was higher in DLB patients than in controls (48.9%, 25.7%; p = 0.035). PPH and OH were independently associated with a diagnosis of DLB (odds ratio [OR]:10.26 confidence interval [CI]%95 3.02–34.82; p < 0.001, and OR:2.22 CI%95 1.2–4.12; p = 0.012, respectively) after adjustment for age, number of medications, use of anti-psychotics drugs, angiotensin receptor blockers, and beta blockers. In conclusion, the study demonstrated that PPH was the most common finding of cardiovascular autonomic dysfunction, followed by OH and SH in older patients with DLB. Given the potential complications of postural blood pressure changes and PPH in such patients, cardiovascular autonomic dysfunction should be evaluated in patients with DLB.
The critical dynamics of hippocampal seizures
Authors: Lepeu Gregory , van Maren Ellen , Slabeva Kristina , Friedrichs-Maeder Cecilia , Fuchs Markus , Z’Graggen Werner J. , Pollo Claudio , Schindler Kaspar A. , Adamantidis Antoine , Proix Timothée , Baud Maxime O. 
Published: August 2024

AbstractEpilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability. Whether such dynamical signatures can be measured before impending seizures remains uncertain. Here, we verified that predictions on bifurcations applied to the onset of hippocampal seizures, providing concordant results from in silico modeling, optogenetics experiments in male mice and intracranial EEG recordings in human patients with epilepsy. Leveraging pharmacological control over neural excitability, we showed that the boundary between physiological excitability and seizures can be inferred from dynamical signatures passively recorded or actively probed in hippocampal circuits. Of importance for the design of future neurotechnologies, active probing surpassed passive recording to decode underlying levels of neural excitability, notably when assessed from a network of propagating neural responses. Our findings provide a promising approach for predicting and preventing seizures, based on a sound understanding of their dynamics.
PTPN2 copper-sensing relays copper level fluctuations into EGFR/CREB activation and associated CTR1 transcriptional repression
Authors: Ross Matthew O. , Xie Yuan , Owyang Ryan C. , Ye Chang , Zbihley Olivia N. P. , Lyu Ruitu , Wu Tong , Wang Pingluan , Karginova Olga , Olopade Olufunmilayo I. , Zhao Minglei , He Chuan 
Published: August 2024

Abstract
Fluxes in human copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate. We herein apply an unbiased temporal evaluation of the signaling and whole genome transcriptional activities modulated by copper level fluctuations to identify potential copper sensor proteins responsible for driving these activities. We find that fluctuations in physiologically relevant copper levels modulate EGFR signal transduction and activation of the transcription factor CREB. Both intracellular and extracellular assays support Cu1+ inhibition of the EGFR phosphatase PTPN2 (and potentially PTPN1)–via ligation to the PTPN2 active site cysteine side chain–as the underlying mechanism. We additionally show i) copper supplementation drives weak transcriptional repression of the copper importer CTR1 and ii) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper stimulated EGFR/CREB signaling and CTR1 expression.
Structural insights into the mechanism and dynamics of proteorhodopsin biogenesis and retinal scavenging
Authors: Hirschi Stephan , Lemmin Thomas , Ayoub Nooraldeen , Kalbermatter David , Pellegata Daniele , Ucurum Zöhre , Gertsch Jürg , Fotiadis Dimitrios 
Published: August 2024

AbstractMicrobial ion-pumping rhodopsins (MRs) are extensively studied retinal-binding membrane proteins. However, their biogenesis, including oligomerisation and retinal incorporation, remains poorly understood. The bacterial green-light absorbing proton pump proteorhodopsin (GPR) has emerged as a model protein for MRs and is used here to address these open questions using cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulations. Specifically, conflicting studies regarding GPR stoichiometry reported pentamer and hexamer mixtures without providing possible assembly mechanisms. We report the pentameric and hexameric cryo-EM structures of a GPR mutant, uncovering the role of the unprocessed N-terminal signal peptide in the assembly of hexameric GPR. Furthermore, certain proteorhodopsin-expressing bacteria lack retinal biosynthesis pathways, suggesting that they scavenge the cofactor from their environment. We shed light on this hypothesis by solving the cryo-EM structure of retinal-free proteoopsin, which together with mass spectrometry and MD simulations suggests that decanoate serves as a temporary placeholder for retinal in the chromophore binding pocket. Further MD simulations elucidate possible pathways for the exchange of decanoate and retinal, offering a mechanism for retinal scavenging. Collectively, our findings provide insights into the biogenesis of MRs, including their oligomeric assembly, variations in protomer stoichiometry and retinal incorporation through a potential cofactor scavenging mechanism.
Self-reporting photodynamic nanobody conjugate for precise and sustainable large-volume tumor treatment
Authors: Chen Yingchao , Xiong Tao , Peng Qiang , Du Jianjun , Sun Wen , Fan Jiangli , Peng Xiaojun 
Published: August 2024

AbstractNanobodies (Nbs), the smallest antigen-binding fragments with high stability and affinity derived from the variable domain of naturally occurring heavy-chain-only antibodies in camelids, have been shown as an efficient way to improve the specificity to tumors for photodynamic therapy (PDT). Nonetheless, the rapid clearance of Nbs in vivo restricts the accumulation and retention of the photosensitizer at the tumor site causing insufficient therapeutic outcome, especially in large-volume tumors. Herein, we develop photodynamic conjugates, MNB-Pyra Nbs, through site-specific conjugation between 7D12 Nbs and type I photosensitizer MNB-Pyra (morpholine-modified nile blue structure connected to pyrazolinone) in a 1:2 ratio. The photosensitizers with long-term retention can be released at the tumor site by reactive oxygen species cleavage after illumination, accompanied with fluorescence recovery for self-reporting the occurrence of PDT. Ultimately, a single dose of MNB-Pyra Nbs demonstrate highly effective tumor suppression with high biosafety in the large-volume tumor models after three rounds of PDT. This nanobody conjugate provides a paradigm for the design of precise long-time retention photosensitizers and is expected to promote the development of PDT.
Discovery of essential kinetoplastid-insect adhesion proteins and their function in Leishmania-sand fly interactions
Authors: Yanase Ryuji , Pruzinova Katerina , Owino Barrack O. , Rea Edward , Moreira-Leite Flávia , Taniguchi Atsushi , Nonaka Shigenori , Sádlová Jovana , Vojtkova Barbora , Volf Petr , Sunter Jack D. 
Published: August 2024

AbstractLeishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide. Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread. One of the key life cycle stages is the haptomonad form, which attaches to insect tissues through its flagellum. This adhesion, conserved across kinetoplastid parasites, is implicated in having an important function within their life cycles and hence in disease transmission. Here, we discover the kinetoplastid-insect adhesion proteins (KIAPs), which localise in the attached Leishmania flagellum. Deletion of these KIAPs impairs cell adhesion in vitro and prevents Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. Additionally, loss of parasite adhesion in the sand fly results in reduced physiological changes to the fly, with no observable damage of the stomodeal valve and reduced midgut swelling. These results provide important insights into a comprehensive understanding of the Leishmania life cycle, which will be critical for developing transmission-blocking strategies.
Cyclododecane-based high-intactness and clean transfer method for fabricating suspended two-dimensional materials
Authors: Wang Zhao , Liu Wenlin , Shao Jiaxin , Hao He , Wang Guorui , Zhao Yixuan , Zhu Yeshu , Jia Kaicheng , Lu Qi , Yang Jiawei , Zhang Yanfeng , Tong Lianming , Song Yuqing , Sun Pengzhan , Mao Boyang , Hu Chenguo , Liu Zhongfan , Lin Li , Peng Hailin 
Published: August 2024

AbstractThe high-intactness and ultraclean fabrication of suspended 2D materials has always been a challenge due to their atomically thin nature. Here, we present a universal polymer-free transfer approach for fabricating suspended 2D materials by using volatile micro-molecule cyclododecane as the transfer medium, thus ensuring the ultraclean and intact surface of suspended 2D materials. For the fabricated monolayer suspended graphene, the intactness reaches 99% for size below 10 µm and suspended size reaches 36 µm. Owing to the advantages of ultra-cleanness and large size, the thermal conductivity reaches 4914 $${\rm{W}}\,{{\rm{m}}}^{-1}{{\rm{K}}}^{-1}$$
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at 338 K. Moreover, this strategy can also realize efficient batch transfer of suspended graphene and is applicable for fabricating other 2D suspended materials such as MoS2. Our research not only establishes foundation for potential applications and investigations of intrinsic properties of large-area suspended 2D materials, but also accelerates the wide applications of suspended graphene grid in ultrahigh-resolution TEM characterization.
Coordination of shoot apical meristem shape and identity by APETALA2 during floral transition in Arabidopsis
Authors: Bertran Garcia de Olalla Enric , Cerise Martina , Rodríguez-Maroto Gabriel , Casanova-Ferrer Pau , Vayssières Alice , Severing Edouard , López Sampere Yaiza , Wang Kang , Schäfer Sabine , Formosa-Jordan Pau , Coupland George 
Published: August 2024

AbstractPlants flower in response to environmental signals. These signals change the shape and developmental identity of the shoot apical meristem (SAM), causing it to form flowers and inflorescences. We show that the increases in SAM width and height during floral transition correlate with changes in size of the central zone (CZ), defined by CLAVATA3 expression, and involve a transient increase in the height of the organizing center (OC), defined by WUSCHEL expression. The APETALA2 (AP2) transcription factor is required for the rapid increases in SAM height and width, by maintaining the width of the OC and increasing the height and width of the CZ. AP2 expression is repressed in the SAM at the end of floral transition, and extending the duration of its expression increases SAM width. Transcriptional repression by SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) represents one of the mechanisms reducing AP2 expression during floral transition. Moreover, AP2 represses SOC1 transcription, and we find that reciprocal repression of SOC1 and AP2 contributes to synchronizing precise changes in meristem shape with floral transition.