bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapidly progressive coronary atherosclerosis in a young male: a retrospective advanced CCT phenotype analysis
Authors: Lorenzatti Daniel , Filtz Annalisa , Latib Azeem , DeRose Joseph , Dey Damini , Berman Daniel S. , Garcia Mario J. , Slipczuk Leandro
Published: August 2024

We present a real-life case of a very young man with multiple risk factors who progressed rapidly from minimally obstructive non-calcified plaque on computed tomography angiography (CCTA) to severe three-vessel coronary disease presenting with STEMI. It questions the reliability of zero coronary calcium in high-risk subgroups like familial hypercholesterolemia, high Lp(a), and the young. While CCTA can accurately visualize non-calcified plaque, its interpretation requires expertise and clinical judgment should consider both imaging and clinical risk factors for management. Advanced plaque quantification, peri-coronary (PCAT), and epicardial (EAT) adipose tissue could help better-stratified patients but the evidence-based clinical application remains unknown.
A values-based approach to designing military autonomous systems
Authors: Boshuijzen-van Burken Christine , Spruit Shannon , Geijsen Tom , Fillerup Lotte
Published: August 2024

Our research is a value sensitive based approach to designing autonomous systems in a military context. Value sensitive design is an iterative process of conceptual, empirical and technical considerations. We enhance value sensitive design with Participatory Value Evaluation. This allows us to mine values of a large unorganized stakeholder group relevant to our context of research, namely Australian citizens. We found that value prioritizations differ depending on the context of use and that no one value fits all autonomous systems. General ethical frameworks can serve as high level guiding principles, but when it comes to actual technologies, a more nuanced and granulated approach to selecting and incorporating values is needed. Our research contributes to a greater awareness of the importance of inclusion of values in autonomous systems design in the context of defence. We suggest relevant frameworks and methods for values-based autonomous military systems design in the context of Australia, which may serve as a blueprint for other countries. Finally, we provide suggestions on how to operationalise values in systems design, as this is underrepresented in the current literature.
Improving estimation for asymptotically independent bivariate extremes via global estimators for the angular dependence function
Authors: Murphy-Barltrop C. J. R. , Wadsworth J. L. , Eastoe E. F.
Published: August 2024

Modelling the extremal dependence of bivariate variables is important in a wide variety of practical applications, including environmental planning, catastrophe modelling and hydrology. The majority of these approaches are based on the framework of bivariate regular variation, and a wide range of literature is available for estimating the dependence structure in this setting. However, such procedures are only applicable to variables exhibiting asymptotic dependence, even though asymptotic independence is often observed in practice. In this paper, we consider the so-called ‘angular dependence function’; this quantity summarises the extremal dependence structure for asymptotically independent variables. Until recently, only pointwise estimators of the angular dependence function have been available. We introduce a range of global estimators and compare them to another recently introduced technique for global estimation through a systematic simulation study, and a case study on river flow data from the north of England, UK.
Fabrication of luminescent disc-shaped microstructures via wet-chemical etching of hybrid sol–gel layers for potential photonic applications
Authors: Duda Łukasz , Rola Krzysztof , Łukomski Michał , Gawlik Andrzej , Olszewski Jacek , Czajkowski Maciej , Cybińska Joanna , Guzik Małgorzata
Published: August 2024

Sol–gel materials based on SiO2 and TiO2 precursors are attractive as a new platform for planar photonics. Particularly interesting are those based on organically modified silica (ORMOSIL), which may improve the luminescent properties of organic dyes. However, their microstructurization remains a challenge as it requires optimization of various technological stages. Here, we report the structurization of thin layers based on ORMOSIL precursor and titanium(IV) ethoxide (TET) containing luminescent rhodamine B (RhB) dye. Films were fabricated using sol–gel synthesis and dip-coating method. Depending on the time of annealing performed at 200 °C, layers with different thicknesses (300–760 nm) and refractive indices (RI) (1.51–1.68) were obtained. Combining photolithography and wet-chemical etching processes made it possible to fabricate well-separated sol–gel waveguides and discs of different diameters. The etching time in buffered hydrofluoric acid (BHF) affected the depth of the etched luminescent microstructures. Additionally, it was found that a longer layer’s annealing time increased the etching selectivity of the substrate over the sol–gel layer. This enabled the obtaining of under-etched sol–gel goblet microstructures. Selected samples were investigated using scanning electron microscopy (SEM). UV–Vis photoluminescence measurements showed that long heat treatment also influenced the emission spectrum’s shape. The stability of the films under ambient conditions was established using spectroscopic ellipsometry. It was proven that films heat-treated at 200 °C did not change their properties during storage time of around 2 months. Relatively high RI, luminescent properties, and structurization potential make these microstructures interesting for application in integrated photonic devices, e.g., light amplifiers or sensing systems.
Enriching satellite image annotations of forests with keyphrases from a specialized corpus
Authors: Neptune Nathalie , Mothe Josiane
Published: August 2024

The automatic annotation of changes in satellite images requires examples of appropriate annotations. Alternatively, keyphrases extracted from a specialized corpus can serve as candidates for image annotation models. In the case of detecting deforestation in satellite images, there is a rich scientific literature available on the topic that may serve as a corpus for finding candidate annotations. We propose a method that utilizes a deep learning technique for change detection and visual semantic embedding. This method is combined with an information retrieval framework to find annotations for pairs of satellite images showing forest changes. Our evaluation is based on a dataset of image pairs from the Amazon rainforest and shows that keyphrases provide richer semantic information without any negative impact on the annotation compared to annotating with single words.
Fine structures of a solar type III radio bursts observed with LOFAR
Authors: Dabrowski Bartosz , Wolowska Aleksandra , Vocks Christian , Magdalenić Jasmina , Zhang Peijin , Flisek Pawel , Bröse Malte , Morosan Diana E. , Krankowski Andrzej , Fron Adam , Mann Gottfried , Zucca Pietro , Bisi Mario , Fallows Richard , Gallagher Peter , Marqué Christophe , Matyjasiak Barbara , Rothkaehl Hanna
Published: August 2024

We present spectral and imaging LOFAR (LOw-Frequency ARray) observations in the 20 – 40 MHz range of solar radio bursts fine structures, such as flag-like, sail-like, and dot-like that appeared on 8 April 2019. These structures were associated with type III solar radio bursts that occurred in the 40 – 80 MHz band. The mean duration and spectral widths of the fine structures range from 1.0 to 3.4 s and from 0.3 to 0.9 MHz, respectively. Additionally, we investigated the radio images of eight fine structures – two flags, two sails and four dots. This allowed us to determine their emission source sizes, which ranged from 240 to 392 arcmin

$${}^2$$

2

, and their frequencies from 25.58 to 39.25 MHz as well as their location. They occurred on the east side of the Sun and were most likely associated with an emerging active region NOAA AR 12738, where a weak B1.7 flare was observed.
Elimination of sugarcane mosaic virus, sugarcane yellow leaf virus, and co-infections in sugarcane (Saccharum spp. hybrids) shoot tips via osmo- and cryo-therapy
Authors: Cele Khethumusa H. , Ghai Meenu , Snyman Sandra J.
Published: August 2024

Cryopreservation for sugarcane (Saccharum spp. hybrids) germplasm conservation is well established. Virus elimination using droplet-vitrification (D-V) and cryo- or osmo-therapy has only been recently reported for sugarcane mosaic virus (SCMV). In this study, exposing large (3 mm) in vitro shoot tips of cultivars N12, N19, N58, and NCo376 infected with sugarcane yellow leaf virus (SCYLV) and NCo376 co-infected with SCMV and SCYLV were tested for virus elimination using both of the above-mentioned techniques. Cryo-therapy involved the exposure of infected in vitro shoot tips to the D-V protocol followed by recording recovery and virus-free shoot tips 16 wk after treatment. Osmo-therapy, consisting of the same treatment as cryo-therapy without immersion in liquid nitrogen (LN), was included for comparative purposes. Cryo-therapy resulted in 100% of the recovered shoots being SCYLV-free in cultivars N19, N58, and NCo376 and 83% in N12 when compared with untreated material. Osmo-therapy showed 58% (N12), 91% (N19 and N58), and 100% (NCo376) of shoots being clear of SCYLV when compared with untreated in vitro control plants (0 to 8%). Both techniques reduced the regrowth levels of treated shoot tips (22 to 57% recovery) when compared with untreated controls (92 to 97%). A novel finding of the study was that NCo376 co-infected with SCMV and SCYLV showed 100% virus-free recovered shoots after cryo-therapy and 92 to 100% of healthy shoots after osmo-therapy, compared with controls, which had 17 to 42% virus-free shoots. Plants from all cultivars that were re-tested 4 mo after hardening maintained their virus-free status. The described techniques for virus eradication offer a promising solution for the provision of clean vegetative planting propagules and safer germplasm exchange.
Psychological impact of exceptional response in people with advanced cancer: a qualitative exploration
Authors: Wahab Sakeenah , Joshua Anthony , Dhillon Haryana M. , Barnet Megan
Published: August 2024

Background

In the cancer context, exceptional response incorporates unusual or unexpected response to anti-cancer treatment. For this study, exceptionally ‘good’ responses are defined as progression-free survival of more than three times the median from comparable trials. We aimed to explore how people meeting the definition of exceptional response to systemic cancer treatment experience adjust to their unexpected survivorship.

Methods

Individuals with ‘exceptional response’ to anti-cancer therapy nationally were referred by their treating clinicians to the Exceptional Responders Program. We conducted a qualitative sub-study involving semi-structured interviews with purposively selected participants. Those eligible had metastatic cancer, had survived at least 3 times the expected time since diagnosis, spoke English, and were aged > 18 years. Interviews were audiorecorded, transcribed and analysed thematically; and continued until thematic saturation was achieved.

Results

Twenty participants were interviewed. Thirteen were male (65%) with a median age of 63 years. Median time since cancer diagnosis was 6.5 years (range 3–18); survival times ranged between 3 and 10 times that expected. We identified four themes which varied in importance between individuals and over time.

Conclusion

Exceptional responders may benefit from routine screening of distress and unmet needs to provide psychosocial support. Clinical services must focus on first capturing and then tailoring care to meet the diverse needs of this growing cohort.

Implications for cancer survivors

Adjustment to a diagnosis of advanced cancer and subsequent unexpected long-term survival is an often isolating experience and is common amongst exceptional responders. Seeking psychological and social support may assist with adjustment.
Scalable Ammonia Synthesis in Fermentors Using Quantum Dot-Azotobacter vinelandii Hybrids
Authors: Kim Jayeong , Lee Byunghyun , Kim Gui-Min , Lee Ilsong , Lee Sang Yup , Choi Kyeong Rok , Lee Doh C.
Published: August 2024

This study introduces a scalable synthesis of ammonia through photochemical reactions, wherein nitrogen-fixing bacterial cells, Azotobacter vinelandii (A. vinelandii), form hybrids with colloidal quantum dots (QDs). Irradiation of the QD-A. vinelandii hybrids with visible light is found to significantly enhance ammonia production efficiency. The inherently low ammonia conversion rate of wild-type A. vinelandii is substantially increased upon incorporation of QDs. This increase is attributed to the electron transfer from QDs within the bacterial cells to intracellular bio-components. Transferring this chemistry to a large-scale reaction presents a tremendous challenge, as it requires precise control over the growth conditions. We explore the scalability of the QD-A. vinelandii hybrids by conducting the photochemical reaction in a 5-L fermentor under various parameters, such as dissolved oxygen, nutrient supply, and pH. Interestingly, ammonia was produced in media depleted of carbon sources. Consequently, a two-step fermentation process was designed, enabling effective ammonia production. Our findings demonstrate that the QD-A. vinelandii hybrid system in a bioreactor setup achieves an ammonia turnover frequency of 11.96 s−1, marking a more than sixfold increase in efficiency over that of nitrogenase enzymes alone. This advancement highlights the potential of integrating biological and nanotechnological elements for scalable ammonia production processes.
The Role of Virtual Reality in the Management of Irritable Bowel Syndrome
Authors: Suchak Karisma K. , Almario Christopher V. , Liran Omer , Chernoff Robert , Spiegel Brennan R.
Published: August 2024

Purpose of Review

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that significantly impacts health-related quality of life (HRQOL). This article explores the potential role of virtual reality (VR)-based cognitive behavioral therapy (CBT) in treating patients with IBS.

Recent Findings

While CBT is a proven, skills-based therapy approach that modifies behaviors and alters dysfunctional thinking patterns to influence the gut-brain axis and improve IBS symptoms, it is rarely prescribed given a paucity of CBT-trained clinicians. We developed a novel VR program that delivers a standardized CBT program over an 8-week period to help patients manage their symptoms. In initial qualitative validation testing, patients expressed positive perceptions about using VR CBT for IBS.

Home-based, standardized VR CBT has the potential to be an effective and scalable treatment option for patients with IBS. While initial studies have shown proof-of-concept definitive randomized controlled trials are needed to demonstrate the efficacy of self-administered VR CBT in IBS.
Yoga in Pediatric Gastroenterology
Authors: Peropat Francis , Abbas Mazen I. , Perez Maria E. , Yu Elizabeth L. , Leiby Alycia
Published: August 2024

Purpose of Review

Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders.

Recent Findings

Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures.

Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.
Expression of Caseicin from Lacticaseibacillus casei and Lacticaseibacillus zeae Provides Insight into Antilisterial Class IIa Bacteriocins
Authors: Salini Francesco , Vermeulen Ross , du Preez van Staden Anton , Comi Giuseppe , Iacumin Lucilla , Dicks Leon M. T.
Published: August 2024

In this study, an in silico screening approach was employed to mine potential bacteriocin clusters in genome-sequenced isolates of Lacticaseibacillus zeae UD 2202 and Lacticaseibacillus casei UD 1001. Two putative undescribed bacteriocin gene clusters (Cas1 and Cas2) closely related to genes encoding class IIa bacteriocins were identified. No bacteriocin activity was recorded when cell-free supernatants of strains UD 2202 and UD 1001 were tested against Listeria monocytogenes. Genes encoding caseicin A1 (casA1) and caseicin A2 (casA2) were heterologously expressed in Escherichia coli BL21 (DE3) using the nisin leader peptide cloned in-frame to the C-terminal of the green fluorescent gene (mgfp5). Nisin protease (NisP) was used to cleave caseicin A1 (casA1) and caseicin A2 (casA2) from GFP-Nisin leader fusion proteins. Both heterologously expressed peptides (casA1 and casA2) inhibited the growth of L. monocytogenes, suggesting that casA1 and casA2 are either silent in the wild-type strains or are not secreted in an active form. The minimum inhibitory concentration (MIC) of casA1 and casA2, determined using HPLC-purified peptides, ranged from < 0.2 µg/mL to 12.5 µg/mL when tested against Listeria ivanovii, Listeria monocytogenes, and Listeria innocua, respectively. A higher MIC value (25 µg/mL) was recorded for casA1 and casA2 when Enterococcus faecium HKLHS was used as the target. The molecular weight of heterologously expressed casA1 and casA2 is 5.1 and 5.2 kDa, respectively, as determined with tricine-SDS-PAGE. Further research is required to determine if genes within Cas1 and Cas2 render immunity to other class IIa bacteriocins.
Puddles, creeks, and drainage: connected histories of water and malaria in Zanzibar, 1910–2021
Authors: Graboyes Melissa , Meta Judith N. , Clarke Rhaine , Bird Margaret , McCann Lily
Published: August 2024

This article draws on a combination of archival and oral sources in order to highlight the connected histories of water and malaria on the Indian Ocean island of Zanzibar (Unguja) over the past century. We argue that in both the past and the present, water and malaria have been deeply connected, through the lifecycle of the disease, through control measures enacted, and in how Zanzibari residents continue to talk about the relationship between rain, puddles, stagnant water, and disease. Archival sources show that between roughly 1913 and 1957, the British colonial government managed malaria by managing water. That entailed a focus on watery breeding sites that included attention to both the micro: cattle hoofprints, and the macro: a multi-decade drainage of the tidal creek and surrounding swamp. These water-based malaria control efforts were limited in their efficacy by being geographically restricted to urban Zanzibar Town, and often limited to just the Stone Town area. 98 interviews conducted with Zanzibaris about malaria indicate that people continue to draw strong connections between malaria and the environment (mazingira), and that they most commonly discuss water’s relationship with malaria in terms of puddles (dimbwi/madimbwi), small puddles (kidimbwi/vidimbwi) and stagnant water (maji yaliyotuama).
How is political trust associated with economic and environmental policy prioritization? A longitudinal analysis between 2017 and 2022
Authors: Ahonen Sami , Koivula Aki , Sivonen Jukka
Published: August 2024

In this article, we examine the longitudinal development of economy-over-environment policy priorities in Finland during a period marked by several significant adverse societal events. In addition, we explore the influence of political trust on these priorities over time. We utilize a five-round panel dataset comprising 2155 observations (N = 431) to examine both within-individual and between-individual variations from late 2017 to early 2023. Our findings reveal a significant increase in the prioritization of the economy in each observation period following the COVID-19 outbreak. However, this trend is not observed among individuals with high levels of political trust. The within-individual analysis indicates that high political trust moderates, rather than causes, higher economy-over-environment prioritization. Our study highlights the significance of political trust as a preventing factor against the deprioritization of environmental policies, particularly when societies confront significant and intersecting adverse events.
Response to the detection of Fusarium dieback associated with ambrosia beetles on Acer negundo in New South Wales
Authors: Callaghan Sophia , Carnegie Angus J. , Gillespie Peter , Mulholland Shannon , Nagel Matthew , Sargeant David , Daly Andrew , Wildman Ossie
Published: August 2024

Symptoms consistent with polyphagous shot hole borer (Euwallacea fornicatus) and Fusarium dieback (Fusarium euwallaceae), recognised as high priority environmental pests for Australia, were observed on a single box elder (Acer negundo) tree in Sydney, New South Wales, in March 2022 during routine forest biosecurity surveillance. Delimiting surveys were undertaken around the Sydney basin, extending radially from the original box elder, resulting in the detection of a further three box elder and one tuckeroo (Cupaniopsis anacardioides) with suspicious symptoms. Samples were taken from the five trees and associated beetles diagnosed using morphological and molecular methods. Associated Fusarium-like fungi were identified according to phylogenetic inference using regions of the internal transcribed spacer, as well as the translation elongation factor 1-α and RNA polymerase II genes. The tea shot hole borer, Euwallacea perbrevis, was identified along with its known fungal mutualist, Fusarium obliquiseptatum. This pair have been reported in Queensland on avocado (Persea americana) and tuckeroo, and there are unpublished records of E. perbrevis from northern NSW, but this is the first report of both species occurring simultaneously in NSW. The biosecurity response following the initial detection, including the establishment of an Incident Management Team, surveillance, diagnostics, and stakeholder engagement, is discussed. This paper highlights the importance of surveillance for early detection of invasive pests and biosecurity systems and processes for enabling a timely response.
Extended version—to be, or not to be stateful: post-quantum secure boot using hash-based signatures
Authors: Wagner Alexander , Oberhansl Felix , Schink Marc
Published: August 2024

While research in PQC has gained significant momentum, its adoption in real-world products is slow. This is largely due to concerns about practicability and maturity. The secure boot process of embedded devices is one scenario where such restraints can result in fundamental security problems. In this work, we present a flexible hardware/software co-design for HBS schemes which enables the transition to a post-quantum secure boot today. These signature schemes stand out due to their straightforward security proofs and are on the fast track to standardisation. Unlike previous work, we exploit the performance intensive similarities of the stateful LMS and XMSS schemes as well as the stateless$$\text {SPHINCS}^{+}$$SPHINCS+scheme. Thus, we enable designers to use a stateful or stateless scheme depending on the constraints of each individual application. To demonstrate the feasibility of our approach, we compare our results with hardware accelerated implementations of classical asymmetric algorithms. Further, we outline the use of different HBS schemes during the boot process. We compare different schemes, show the importance of parameter choices, and demonstrate the performance gain with different levels of hardware acceleration.
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

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

The 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

This 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

Retention 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

The 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

Cardiovascular 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

Epilepsy 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

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

Microbial 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

Nanobodies (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

Leishmania 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

The 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

Plants 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.
Decoding the genomic landscape of chromatin-associated biomolecular condensates
Authors: Yu Zhaowei , Wang Qi , Zhang Qichen , Tian Yawen , Yan Guo , Zhu Jidong , Zhu Guangya , Zhang Yong
Published: August 2024

Biomolecular condensates play a significant role in chromatin activities, primarily by concentrating and compartmentalizing proteins and/or nucleic acids. However, their genomic landscapes and compositions remain largely unexplored due to a lack of dedicated computational tools for systematic identification in vivo. To address this, we develop CondSigDetector, a computational framework designed to detect condensate-like chromatin-associated protein co-occupancy signatures (CondSigs), to predict genomic loci and component proteins of distinct chromatin-associated biomolecular condensates. Applying this framework to mouse embryonic stem cells (mESC) and human K562 cells enable us to depict the high-resolution genomic landscape of chromatin-associated biomolecular condensates, and uncover both known and potentially unknown biomolecular condensates. Multi-omics analysis and experimental validation further verify the condensation properties of CondSigs. Additionally, our investigation sheds light on the impact of chromatin-associated biomolecular condensates on chromatin activities. Collectively, CondSigDetector provides an approach to decode the genomic landscape of chromatin-associated condensates, facilitating a deeper understanding of their biological functions and underlying mechanisms in cells.