bluuebunny/crossref_metadata_2025 huggingface dataset:
Flood timing and flood loss impact on effectiveness of florpyrauxifen-benzyl coated on urea in rice
Authors: Cotter Bodie L. , Norsworthy Jason K. , Butts Thomas R. , Roberts Trenton L. , Mauromoustakos Andy
Published: May 2024

Florpyrauxifen-benzyl has generated complaints and concerns around rice injury and off-target movement to soybean since its commercial launch in 2018. Developing a precise method for applying florpyrauxifen-benzyl was imperative for its continued use. Experiments were conducted in 2020 and 2021 to evaluate rice weed control as influenced by preflood application interval and flood loss following florpyrauxifen-benzyl at 30 g ai ha−1 applied as a spray or coated on urea. In a preflood application experiment, coating florpyrauxifen-benzyl on urea and applying it the day of flood establishment and 5 and 10 d prior to flooding (DPTF) resulted in lower yellow nutsedge, broadleaf signalgrass, and barnyardgrass control than when the herbicide was spray at 3 and 5 wk after final treatment (WAFT). Coating florpyrauxifen-benzyl onto urea provided only 61% to 63% yellow nutsedge control at 3 and 5 WAFT, which was 35 to 37 percentage points lower than when the spray was applied at 5 or 10 DPTF. Likewise, rice yields following applications of florpyrauxifen-benzyl coated onto urea were 1,200 kg ha−1 less than yields following spray applications. Florpyrauxifen-benzyl coated onto urea and clomazone provided lower levels of weed control than spraying the herbicide alone, suggesting an explanation for the yield losses. The timing of flood loss experiment suggested that when florpyrauxifen-benzyl coated onto urea at 30 g ai ha−1 was applied preflood and flood was relinquished at 2 h, 24 h, and 7 d after flood establishment, hemp sesbania and yellow nutsedge control were not affected. However, loss of floodwater 2 h after flood establishment resulted in lower barnyardgrass control than when the flood was lost 24 h and 7 d after flooding. Generally, the period between a herbicide application and flooding completion should be minimized to aid in weed control. These results indicate the importance of maintaining a flood for weed control and nutrient management.
Ressourcenorientiert Testen? Effekte des Instruktionsdesigns auf die Testleistung
Authors: Schulze Sarah , Kuhl Jan
Published: May 2024

Zusammenfassung: Testaufgaben stellen – ebenso wie Lernmaterialien und Lernsettings – hohe Anforderungen an die Informationsverarbeitung von Schülerinnen und Schülern. Mit dieser kognitiven Belastung beim Lernen und Problemlösen befasst sich die Cognitive Load Theory bereits seit einiger Zeit, sodass mittlerweile zahlreiche Befunde vorliegen. Auf dieser Basis wurden Gestaltungsprinzipien formuliert, an denen Unterricht und Lernmaterialien ausgerichtet werden sollten. Dabei geht es stets darum, die kognitiven Ressourcen möglichst effizient für die Auseinandersetzung mit dem Lerninhalt zu nutzen. Im Sinne der Konstruktvalidität sollte dies auch bei diagnostischen Verfahren angestrebt werden. So sollten die Testergebnisse ausschließlich von dem Zielkonstrukt, z.B. von den mathematischen Kompetenzen, bestimmt sein und nicht von entfernten Merkmalen wie dem Arbeitsgedächtnis (AG). Welchen Einfluss die ressourcenorientierte Gestaltung auf die Testergebnisse in diagnostischen Tests haben können, ist bisweilen kaum untersucht. Daher wurde in der vorliegenden Arbeit ein standardisierter Test zur Erfassung mathematischer Basiskompetenzen nach ressourcenschonenden Prinzipen adaptiert. Zur Prüfung der Effekte auf die Testleistung wurde eine Gruppenstudie mit 261 Schülerinnen und Schülern ( M = 6.95 Jahre) durchgeführt. Zusätzlich wurden AG-Funktionen als Kontrollvariablen erfasst. Die regressionsanalytischen Ergebnisse bilden einen signifikanten Effekt der Bedingung zu Gunsten der ressourcenschonenden Adaption ab. Eine Interaktion zwischen Testversion und AG wurde nicht gefunden. Somit schneiden die Schülerinnen und Schüler im adaptierten Test unabhängig von ihren AG-Funktionen besser ab. Lehrkräfte und andere Praktikerinnen und Praktiker sollten für derartige Effekte sensibilisiert sein und Testergebnisse auch unter dem Gesichtspunkt der erforderlichen Zugangsfertigkeiten einordnen.
Roles of Gravity Waves in Preconditioning of a Stratospheric Sudden Warming
Authors: Okui H. , Koshin D. , Watanabe S. , Sato K.
Published: May 2024

As well as strong upward propagation of planetary waves from the troposphere, the state of the stratospheric mean flow has been recognized as a key factor for the occurrence of stratospheric sudden warmings (SSWs). The modification of the mean flow to a suitable state for an SSW occurrence is called “vortex preconditioning.” Recently, increasing attention has been paid to the role of gravity waves (GWs) in the preconditioning mechanism. However, because of the limited availability of data sets covering the whole neutral atmosphere, much uncertainty still exists in the role of GWs in the preconditioning. The aim of this study is to investigate the mechanism of modification of the mean flow in the stratosphere and mesosphere before SSWs from a climatological viewpoint and elucidate the role of GWs in it. We use two state‐of‐the‐art data sets covering the whole neutral atmosphere: a 17‐year medium‐resolution reanalysis data set and the output data from hindcast simulations performed with a GW‐permitting general circulation model. It is shown that the second principal component of the zonal‐mean zonal wind in the stratosphere and mesosphere tends to show a maximum prior to an SSW, characterizing preconditioning. GW forcing alters the structure of the upper part of the jet and contributes to the preconditioning along with planetary waves. Comparison of GW forcing between the reanalysis and GW‐permitting model suggests that the magnitude of parameterized GW forcing is approximately half that of the GW forcing in the polar upper stratosphere where the forcing is responsible for the preconditioning.
Earthquake Relocations Delineate a Discrete Fault Network and Deformation Corridor Throughout Southeast Alaska and Southwest Yukon
Authors: Biegel K. M. , Gosselin J. M. , Dettmer J. , Colpron M. , Enkelmann E. , Caine J. S.
Published: May 2024

Deformation in southeastern Alaska and southwest Yukon is governed by the subduction and translation of the Pacific‐Yakutat plates relative to the North American plate in the St. Elias region. Despite notable historical seismicity and major regional faults, studies of the region between the Fairweather and Denali faults are complicated by glacial coverage and the remote setting. In the last decade, significant improvements have been made to the density of regional broadband seismometer networks. We relocate more than 5,000 earthquakes between 2010 and 2021 in the region of southeastern Alaska and southwestern Yukon utilizing these improved seismic networks. With reductions in catalog uncertainty, particularly in depth, we quantify the thickness of the seismogenic layer in the crust throughout the region and locate seismicity on a shallow network of upper‐crustal faults. Relocated earthquakes, combined with an updated focal‐mechanism catalog, permit estimating and classifying motion of active faults. This includes mapping the Totschunda‐Fairweather “Connector” fault, which plays an important role in explaining regional deformation, and identifying new faults like the Kathleen Lake fault. We draw similarities between our seismic observations and simplified conceptual models of regional tectonics, which describe a dominant transpressional regime and localized slip partitioning. Our results support a hypothesis where current deformation is taking place on a well‐defined and evolved network of shallow faults in the corridor between the Totschunda‐Fairweather “Connector” and Denali faults.
How to Select an Objective Function Using Information Theory
Authors: Hodson Timothy O. , Over Thomas M. , Smith Tyler J. , Marshall Lucy M.
Published: May 2024

In machine learning or scientific computing, model performance is measured with an objective function. But why choose one objective over another? According to the information‐theoretic paradigm, the “best” objective function is whichever minimizes information loss. To evaluate different objectives, transform them into likelihoods. The ratios of these likelihoods represent how strongly we should prefer one objective versus another, and the log of that ratio represents the relative information loss (or gain) from one objective to another. In plain terms, minimizing information loss is equivalent to minimizing uncertainty, as well as maximizing probability and general utility. We argue that this paradigm is well‐suited to models that have many uses and no definite utility like the complex Earth system models used to understand the effects of climate change. Furthermore, the benefits of “maximizing information and general utility” extend beyond model accuracy to other important considerations including how efficiently the model calibrates, how well it generalizes, and how well it compresses data.
The Inverted U‐Shaped Relationship Between Socio‐Economic Status and Infections During the COVID‐19 Pandemic
Authors: Sun Yelin , Liu Weihang , Zhang Gangfeng , Shi Peijun
Published: May 2024

Although the World Health Organization has declared that the COVID‐19 pandemic no longer qualifies as a global public health emergency, it still needs to explore the response of society to the COVID‐19 pandemic. Socio‐economic status (SES) was proven to be linearly associated with the COVID‐19 pandemic, although this relationship may be more complex due to regional differences. In the study, we analyzed and revealed the effects and mechanisms of SES on infections among low, lower‐middle, upper‐middle and high SES group (LSG, LMSG, UMSG, and HSG, respectively). The results showed that the relationship between SES and infections was inverted U‐shaped, especially in the first three phases. In Phase I, UMSG had the highest number of infections, with an average of 238.31/1M people (95%CI: 135.47–341.15/1M people). In Phases II and III, infections decreased insignificantly with increasing SES (r = −0.01, p = 0.92; r = −0.11, p = 0.22) and the highest number of infections were found in the LMSG. In Phase IV, SES was positively related to the number of infections (r = 0.54, p < 0.001). Furthermore, the nonlinear impact of multiple factors related to SES on the infections explains the complex relationships between SES and infections. SES affected infections mainly through medical resources, demographics and vaccination, and differed across the SES groups. Particularly, demographics could exert an impact on population mobility, subsequently influencing infections in LMSG, with an indirect effect of 0.01 (p < 0.05) in Phase II. This study argues for greater attention to countries with middle SES and the need for future targeted measures to cope with infectious diseases.
Divergence Between Long‐Term and Event‐Scale Nitrate Export Patterns
Authors: Winter Carolin , Jawitz James W. , Ebeling Pia , Cohen Matthew J. , Musolff Andreas
Published: May 2024

The mechanisms driving catchment nitrogen storage and release operate at multiple spatiotemporal scales. Consequently, analyses grounded in different observational timescales can yield discrepant interpretations of underlying mechanisms. To assess the consistency of nitrate export patterns between event‐ and inter‐annual scales, we evaluated multiple years of high‐frequency observations of nitrate concentrations (C) and discharge (Q) including 3,480 discrete discharge events from 28 dominantly agricultural catchments. We observed consistent and often drastic divergence between long‐term and median event‐specific C‐Q patterns. Most catchments showed long‐term enrichment patterns (positive C‐Q slope), but events were, on average, more chemostatic (close‐to‐zero C‐Q slopes). C‐Q slope variability was high for small events but decreased with event magnitude, approaching chemostatic patterns during the largest storms, yielding compelling evidence against nitrate source limitation. We conclude that nitrate export patterns observed at different temporal scales and event magnitudes are controlled by different processes, therefore embedding complementary information.
An InSAR‐GNSS Velocity Field for Iran
Authors: Watson Andrew R. , Elliott John R. , Lazecký Milan , Maghsoudi Yasser , McGrath Jack D. , Walters Richard J.
Published: May 2024

We present average ground‐surface velocities and strain rates for the 1.7 million km2 area of Iran, from the joint inversion of InSAR‐derived displacements and GNSS data. We generate interferograms from 7 years of Sentinel‐1 radar acquisitions, correct for tropospheric noise using the GACOS system, estimate average velocities using LiCSBAS time‐series analysis, tie this into a Eurasia‐fixed reference frame, and perform a decomposition to estimate East and Vertical velocities at 500 m spacing. Our InSAR‐GNSS velocity fields reveal predominantly diffuse crustal deformation, with localized interseismic strain accumulation along the North Tabriz, Main Kopet Dagh, Main Recent, Sharoud, and Doruneh faults. We observe signals associated with recent groundwater subsidence, co‐ and postseismic deformation, active salt diaprism, and sediment motion. We derive high‐resolution strain rate estimates on a country‐ and fault‐scale, and discuss the difficulties of mapping diffuse strain rates in areas with abundant non‐tectonic and anthropogenic signals.
West African Monsoon Dynamics and Its Control on the Stable Oxygen Isotopic Composition of Precipitation in the Late Cenozoic
Authors: Boateng Daniel , Aryee Jeffrey N. A. , Baidu Michael , Arthur Frank , Mutz Sebastian G.
Published: May 2024

This study presents an overview of the Late Cenozoic evolution of the West African Monsoon (WAM), and the associated changes in atmospheric dynamics and oxygen isotopic composition of precipitation (δ18Op). This evolution is established by using the high‐resolution isotope‐enabled GCM ECHAM5‐wiso to simulate the climatic responses to paleoenvironmental changes during the Mid‐Holocene (MH), Last Glacial Maximum (LGM), and Mid‐Pliocene (MP). The simulated responses are compared to a set of GCM outputs from Paleoclimate Model Intercomparison Project Phase 4 (PMIP4) to assess the added value of a high resolution and model consistency across different time periods. Results show WAM magnitudes and pattern changes that are consistent with PMIP4 models and proxy reconstructions. ECHAM5‐wiso estimates the highest WAM intensification in the MH, with a precipitation increase of up to 150 mm/month reaching 25°N during the monsoon season. The WAM intensification in the MP estimated by ECHAM5‐wiso (up to 80 mm/month) aligns with the mid‐range of the PMIP4 estimates, while the LGM dryness magnitude matches most of the models. Despite an enhanced hydrological cycle in MP, MH simulations indicate a ∼50% precipitation increase and a greater northward extent of WAM than the MP simulations. Strengthened conditions of the WAM in the MH and MP result from a pronounced meridional temperature gradient driving low‐level westerly, Sahel‐Sahara vegetation expansion, and a northward shift of the Africa Easterly Jet. The simulated δ18Op values patterns and their relationship with temperature and precipitation are non‐stationarity over time, emphasizing the implications of assuming stationarity in proxy reconstruction transfer functions.
An integrated microfluidic platform for nucleic acid testing
Authors: Sun Antao , Vopařilová Petra , Liu Xiaocheng , Kou Bingqian , Řezníček Tomáš , Lednický Tomáš , Ni Sheng , Kudr Jiří , Zítka Ondřej , Fohlerová Zdenka , Pajer Petr , Zhang Haoqing , Neužil Pavel
Published: May 2024

This study presents a rapid and versatile low-cost sample-to-answer system for SARS-CoV-2 diagnostics. The system integrates the extraction and purification of nucleic acids, followed by amplification via either reverse transcription-quantitative polymerase chain reaction (RT–qPCR) or reverse transcription loop-mediated isothermal amplification (RT–LAMP). By meeting diverse diagnostic and reagent needs, the platform yields testing results that closely align with those of commercial RT-LAMP and RT‒qPCR systems. Notable advantages of our system include its speed and cost-effectiveness. The assay is completed within 28 min, including sample loading (5 min), ribonucleic acid (RNA) extraction (3 min), and RT-LAMP (20 min). The cost of each assay is ≈ $9.5, and this pricing is competitive against that of Food and Drug Administration (FDA)-approved commercial alternatives. Although some RNA loss during on-chip extraction is observed, the platform maintains a potential limit of detection lower than 297 copies. Portability makes the system particularly useful in environments where centralized laboratories are either unavailable or inconveniently located. Another key feature is the platform’s versatility, allowing users to choose between RT‒qPCR or RT‒LAMP tests based on specific requirements.
Individualized prediction models in ADHD: a systematic review and meta-regression
Authors: Salazar de Pablo Gonzalo , Iniesta Raquel , Bellato Alessio , Caye Arthur , Dobrosavljevic Maja , Parlatini Valeria , Garcia-Argibay Miguel , Li Lin , Cabras Anna , Haider Ali Mian , Archer Lucinda , Meehan Alan J. , Suleiman Halima , Solmi Marco , Fusar-Poli Paolo , Chang Zheng , Faraone Stephen V. , Larsson Henrik , Cortese Samuele
Published: May 2024

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (β = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.
Exposure to the parents’ speech is positively associated with preterm infant’s face preference
Authors: Aija Anette , Leppänen Jukka , Aarnos Laura , Hyvönen Mirka , Ståhlberg-Forsén Eva , Ahlqvist-Björkroth Sari , Stolt Suvi , Toome Liis , Lehtonen Liisa
Published: May 2024

Background

The parents’ presence and involvement in neonatal care is a promising approach to improve preterm infants’ neurodevelopmental outcomes. We examined whether exposure to the parents’ speech is associated with the preterm infant’s social-cognitive development.

Methods

The study included infants born before 32 gestational weeks in two neonatal units. Each infant’s language environment was assessed from 16-hour recordings using Language Environment Analysis (LENA®). Parental presence was assessed with Closeness Diary for 14 days during the hospital stay. Attention to faces and non-face patterns was measured at the corrected age of seven months using an eye-tracking disengagement test.

Results

A total of 63 preterm infants were included. Infants were less likely to disengage their attention from faces (M = 0.55, SD = 0.26) than non-face patterns (M = 0.24, SD = 0.22), p < 0.001, d = 0.84. Exposure to the parents’ speech during the neonatal period was positively correlated with the preference for faces over non-face patterns (r
s = 0.34, p = 0.009) and with the preference for parents over unfamiliar faces (r
s = 0.28, p = 0.034).

Conclusion

The exposure to the parents’ speech during neonatal hospital care is a potential early marker for later social development in preterm infants.

Impact

The exposure to the parents’ speech during neonatal intensive care is a potential early marker for optimal social-cognitive development in preterm infants.

This is the first study to show an association between parental vocal contact during neonatal intensive care and early social development (i.e., face preference), measured at seven months of corrected age.

Our findings suggest that we should pay attention to the parents’ vocal contact with their child in the neonatal intensive care unit and identify need for tailored support for face-to-face and vocal contact.
A systematic review of patient-oriented outcomes following complete denture treatment: a comparison between the neutral zone technique and conventional approach
Authors: Limpuangthip Nareudee , Techapiroontong Siraphob , Prawatvatchara Wisarut
Published: May 2024

Objectives

To determine the patient-oriented outcomes after complete denture (CD) treatment using neutral zone (NZ) techniques compared with those of conventional dentures.

Materials and methods

Electronic and hand searches were conducted up to December 2023 based on PICOS criteria. Population (P) was patients with complete edentulism on maxillary and mandibular arches and were either or not wearing CDs. Intervention (I) focused on the fabrication of mandibular and/or maxillary CD using NZ techniques. Comparators (C) included other CD fabrication approaches, such as conventional and simplified techniques, and the use of old or existing CDs. Outcomes (O) were patient-oriented treatment outcomes. Study design (S) included human studies.

Results

Eleven human experimental studies were included. NZ dentures demonstrated better patient-reported outcomes, by providing greater comfort, enhancing denture stability and retention, reducing food traps underneath the denture, as well as improving appearance, chewing efficiency and speech. Objective findings varied, with most studies showing equivalent outcomes for NZ and conventional dentures. However, one study indicated superior, and another demonstrated worse outcomes for NZ dentures.

Conclusions

NZ dentures generally improve patient-reported outcomes more than conventional dentures. However, their impact on objective outcomes compared with a conventional denture remains uncertain.
The importance of murine phospho-MLKL-S345 in situ detection for necroptosis assessment in vivo
Authors: Kelepouras Konstantinos , Saggau Julia , Varanda Ana Beatriz , Zrilic Matea , Kiefer Christine , Rakhsh-Khorshid Hassan , Lisewski Ina , Uranga-Murillo Iratxe , Arias Maykel , Pardo Julian , Tonnus Wulf , Linkermann Andreas , Annibaldi Alessandro , Walczak Henning , Liccardi Gianmaria
Published: May 2024

Necroptosis is a caspase-independent modality of cell death implicated in many inflammatory pathologies. The execution of this pathway requires the formation of a cytosolic platform that comprises RIPK1 and RIPK3 which, in turn, mediates the phosphorylation of the pseudokinase MLKL (S345 in mouse). The activation of this executioner is followed by its oligomerisation and accumulation at the plasma-membrane where it leads to cell death via plasma-membrane destabilisation and consequent permeabilisation. While the biochemical and cellular characterisation of these events have been amply investigated, the study of necroptosis involvement in vivo in animal models is currently limited to the use of Mlkl−/− or Ripk3−/− mice. Yet, even in many of the models in which the involvement of necroptosis in disease aetiology has been genetically demonstrated, the fundamental in vivo characterisation regarding the question as to which tissue(s) and specific cell type(s) therein is/are affected by the pathogenic necroptotic death are missing. Here, we describe and validate an immunohistochemistry and immunofluorescence-based method to reliably detect the phosphorylation of mouse MLKL at serine 345 (pMLKL-S345). We first validate the method using tissues derived from mice in which Caspase-8 (Casp8) or FADD are specifically deleted from keratinocytes, or intestinal epithelial cells, respectively. We next demonstrate the presence of necroptotic activation in the lungs of SARS-CoV-infected mice and in the skin and spleen of mice bearing a Sharpin inactivating mutation. Finally, we exclude necroptosis occurrence in the intestines of mice subjected to TNF-induced septic shock. Importantly, by directly comparing the staining of pMLKL-345 with that of cleaved Caspase-3 staining in some of these models, we identify spatio-temporal and functional differences between necroptosis and apoptosis supporting a role of RIPK3 in inflammation independently of MLKL versus the role of RIPK3 in activation of necroptosis.
Induced dual-target rebalance simultaneously enhances efficient therapeutical efficacy in tumors
Authors: Zhang Xiaoyu , Ding Tianyi , Yang Fan , Xu Haowen , Zhang Jixing , Bai Yiran , Shi Yibing , Yang Jiaqi , Chen Chaoqun , Zhang He
Published: May 2024

Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.
The bacterial metabolite, lithocholic acid, has antineoplastic effects in pancreatic adenocarcinoma
Authors: Schwarcz Szandra , Kovács Patrik , Nyerges Petra , Ujlaki Gyula , Sipos Adrienn , Uray Karen , Bai Péter , Mikó Edit
Published: May 2024

Lithocholic acid (LCA) is a secondary bile acid. LCA enters the circulation after bacterial synthesis in the gastrointestinal tract, reaches distantly located cancer cells, and influences their behavior. LCA was considered carcinogenic, but recent studies demonstrated that LCA has antitumor effects. We assessed the possible role of LCA in pancreatic adenocarcinoma. At the serum reference concentration, LCA induced a multi-pronged antineoplastic program in pancreatic adenocarcinoma cells. LCA inhibited cancer cell proliferation and induced mesenchymal-to-epithelial (MET) transition that reduced cell invasion capacity. LCA induced oxidative/nitrosative stress by decreasing the expression of nuclear factor, erythroid 2-like 2 (NRF2) and inducing inducible nitric oxide synthase (iNOS). The oxidative/nitrosative stress increased protein nitration and lipid peroxidation. Suppression of oxidative stress by glutathione (GSH) or pegylated catalase (pegCAT) blunted LCA-induced MET. Antioxidant genes were overexpressed in pancreatic adenocarcinoma and decreased antioxidant levels correlated with better survival of pancreatic adenocarcinoma patients. Furthermore, LCA treatment decreased the proportions of cancer stem cells. Finally, LCA induced total and ATP-linked mitochondrial oxidation and fatty acid oxidation. LCA exerted effects through the farnesoid X receptor (FXR), vitamin D receptor (VDR), and constitutive androstane receptor (CAR). LCA did not interfere with cytostatic agents used in the chemotherapy of pancreatic adenocarcinoma. Taken together, LCA is a non-toxic compound and has antineoplastic effects in pancreatic adenocarcinoma.
MOG antibody-associated optic neuritis
Authors: Jeyakumar Niroshan , Lerch Magdalena , Dale Russell C. , Ramanathan Sudarshini
Published: May 2024

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MOGAD most frequently presents with optic neuritis (MOG-ON), often with characteristic clinical and radiological features. Bilateral involvement, disc swelling clinically and radiologically, and longitudinally extensive optic nerve hyperintensity with associated optic perineuritis on MRI are key characteristics that can help distinguish MOG-ON from optic neuritis due to other aetiologies. The detection of serum MOG immunoglobulin G utilising a live cell-based assay in a patient with a compatible clinical phenotype is highly specific for the diagnosis of MOGAD. This review will highlight the key clinical and radiological features which expedite diagnosis, as well as ancillary investigations such as visual fields, visual evoked potentials and cerebrospinal fluid analysis, which may be less discriminatory. Optical coherence tomography can identify optic nerve swelling acutely, and atrophy chronically, and may transpire to have utility as a diagnostic and prognostic biomarker. MOG-ON appears to be largely responsive to corticosteroids, which are often the mainstay of acute management. However, relapses are common in patients in whom follow-up is prolonged, often in the context of early or rapid corticosteroid tapering. Establishing optimal acute therapy, the role of maintenance steroid-sparing immunotherapy for long-term relapse prevention, and identifying predictors of relapsing disease remain key research priorities in MOG-ON.
Highly tunable ground and excited state excitonic dipoles in multilayer 2H-MoSe2
Authors: Feng Shun , Campbell Aidan J. , Brotons-Gisbert Mauro , Andres-Penares Daniel , Baek Hyeonjun , Taniguchi Takashi , Watanabe Kenji , Urbaszek Bernhard , Gerber Iann C. , Gerardot Brian D.
Published: May 2024

The fundamental properties of an exciton are determined by the spin, valley, energy, and spatial wavefunctions of the Coulomb-bound electron and hole. In van der Waals materials, these attributes can be widely engineered through layer stacking configuration to create highly tunable interlayer excitons with static out-of-plane electric dipoles, at the expense of the strength of the oscillating in-plane dipole responsible for light-matter coupling. Here we show that interlayer excitons in bi- and tri-layer 2H-MoSe2 crystals exhibit electric-field-driven coupling with the ground (1s) and excited states (2s) of the intralayer A excitons. We demonstrate that the hybrid states of these distinct exciton species provide strong oscillator strength, large permanent dipoles (up to 0.73 ± 0.01 enm), high energy tunability (up to ~200 meV), and full control of the spin and valley characteristics such that the exciton g-factor can be manipulated over a large range (from −4 to +14). Further, we observe the bi- and tri-layer excited state (2s) interlayer excitons and their coupling with the intralayer excitons states (1s and 2s). Our results, in good agreement with a coupled oscillator model with spin (layer)-selectivity and beyond standard density functional theory calculations, promote multilayer 2H-MoSe2 as a highly tunable platform to explore exciton-exciton interactions with strong light-matter interactions.
Single molecule delivery into living cells
Authors: Chau Chalmers C. , Maffeo Christopher M. , Aksimentiev Aleksei , Radford Sheena E. , Hewitt Eric W. , Actis Paolo
Published: May 2024

Controlled manipulation of cultured cells by delivery of exogenous macromolecules is a cornerstone of experimental biology. Here we describe a platform that uses nanopipettes to deliver defined numbers of macromolecules into cultured cell lines and primary cells at single molecule resolution. In the nanoinjection platform, the nanopipette is used as both a scanning ion conductance microscope (SICM) probe and an injection probe. The SICM is used to position the nanopipette above the cell surface before the nanopipette is inserted into the cell into a defined location and to a predefined depth. We demonstrate that the nanoinjection platform enables the quantitative delivery of DNA, globular proteins, and protein fibrils into cells with single molecule resolution and that delivery results in a phenotypic change in the cell that depends on the identity of the molecules introduced. Using experiments and computational modeling, we also show that macromolecular crowding in the cell increases the signal-to-noise ratio for the detection of translocation events, thus the cell itself enhances the detection of the molecules delivered.
Identifying rheological regimes within pyroclastic density currents
Authors: Jones Thomas. J. , Shetty Abhishek , Chalk Caitlin , Dufek Josef , Gonnermann Helge M.
Published: May 2024

Pyroclastic density currents (PDCs) are the most lethal of all volcanic hazards. An ongoing challenge is to accurately forecast their run-out distance such that effective mitigation strategies can be implemented. Central to this goal is an understanding of the flow mobility—a quantitative rheological model detailing how the high temperature gas-pyroclast mixtures propagate. This is currently unknown, yet critical to accurately forecast the run-out distance. Here, we use a laboratory apparatus to perform rheological measurements on real gas-pyroclast mixtures at dynamic conditions found in concentrated to intermediate pumice-rich PDCs. We find their rheology to be non-Newtonian featuring (i) a yield stress where deposition occurs; (ii) shear-thinning behavior that promotes channel formation and local increases in velocity and (iii) shear-thickening behavior that promotes decoupling and potential co-PDC plume formation. We provide a universal regime diagram delineating these behaviors and illustrating how flow can transition between them during transport.
HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes
Authors: DeMarino Catherine , Denniss Julia , Cowen Maria , Norato Gina , Dietrich Devon K. , Henderson Lisa , Gollomp Elyse , Snow Joseph , Pandya Darshan , Smith Bryan , Nath Avindra
Published: May 2024

Human immunodeficiency virus type-1 (HIV-1) is responsible for significant mortality and morbidity worldwide. Despite complete control of viral replication with antiretrovirals, cells with integrated HIV-1 provirus can produce viral transcripts. In a cross-sectional study of 84 HIV+ individuals of whom 43 were followed longitudinally, we found that HIV-1 RNAs are present in extracellular vesicles (EVs) derived from cerebrospinal fluid and serum of all individuals. We used seven digital droplet polymerase chain reaction assays to evaluate the transcriptional status of the latent reservoir. EV-associated viral RNA was more abundant in the CSF and correlated with neurocognitive dysfunction in both, the cross-sectional and longitudinal studies. Sequencing studies suggested compartmentalization of defective viral transcripts in the serum and CSF. These findings suggest previous studies have underestimated the viral burden and there is a significant relationship between latent viral transcription and CNS complications of long-term disease despite the adequate use of antiretrovirals.
The patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
Authors: Hanson Sarah E. , Dowdy Tyrone , Larion Mioara , Doyle Matthew Thomas , Bernstein Harris D.
Published: May 2024

Members of the Omp85 superfamily of outer membrane proteins (OMPs) found in Gram-negative bacteria, mitochondria and chloroplasts are characterized by a distinctive 16-stranded β-barrel transmembrane domain and at least one periplasmic POTRA domain. All previously studied Omp85 proteins promote critical OMP assembly and/or protein translocation reactions. Pseudomonas aeruginosa PlpD is the prototype of an Omp85 protein family that contains an N-terminal patatin-like (PL) domain that is thought to be translocated across the OM by a C-terminal β-barrel domain. Challenging the current dogma, we find that the PlpD PL-domain resides exclusively in the periplasm and, unlike previously studied Omp85 proteins, PlpD forms a homodimer. Remarkably, the PL-domain contains a segment that exhibits unprecedented dynamicity by undergoing transient strand-swapping with the neighboring β-barrel domain. Our results show that the Omp85 superfamily is more structurally diverse than currently believed and suggest that the Omp85 scaffold was utilized during evolution to generate novel functions.
A nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
Authors: Singh Alka , Abhilasha Kandahalli Venkataranganayaka , Acharya Kathya R. , Liu Haibo , Nirala Niraj K. , Parthibane Velayoudame , Kunduri Govind , Abimannan Thiruvaimozhi , Tantalla Jacob , Zhu Lihua Julie , Acharya Jairaj K. , Acharya Usha R.
Published: May 2024

Pancreatic β cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.
Charge density wave ordering in NdNiO2: effects of multiorbital nonlocal correlations
Authors: Stepanov Evgeny A. , Vandelli Matteo , Lichtenstein Alexander I. , Lechermann Frank
Published: May 2024

In this work, we investigate collective electronic fluctuations and, in particular, the possibility of the charge density wave ordering in an infinite-layer NdNiO2. We perform advanced many-body calculations for the ab-initio three-orbital model by taking into account local correlation effects, nonlocal charge and magnetic fluctuations, and the electron-phonon coupling. We find that in the considered material, electronic correlations are strongly orbital- and momentum-dependent. Notably, the charge density wave and magnetic instabilities originate from distinct orbitals. In particular, we show that the correlation effects lead to the momentum-dependent hybridization between different orbitals, resulting in the splitting and shifting of the flat part of the Ni-$${d}_{{z}^{2}}$$

d

z

2

band. This strong renormalization of the electronic spectral function drives the charge density wave instability that is related to the intraband Ni-$${d}_{{z}^{2}}$$

d

z

2

correlations. Instead, the magnetic instability stems from the Ni-$${d}_{{x}^{2}-{y}^{2}}$$

d

x

2

−

y

2

orbital, which remains half-filled through the redistribution of the electronic density between different bands even upon hole doping. Consequently, the strength of the magnetic fluctuations remains nearly unchanged for the considered doping levels. We argue that this renormalization is not inherent to the stoichiometric case but can be induced by hole doping.
Acute cardiovascular and muscular response to rowing ergometer exercise in artificial gravity – a pilot trial
Authors: Frett Timo , Lecheler Leo , Arz Michael , Pustowalow Willi , Petrat Guido , Mommsen Florian , Breuer Jan , Schmitz Marie-Therese , Green David Andrew , Jordan Jens
Published: May 2024

Prolonged immobilization and spaceflight cause cardiovascular and musculoskeletal deconditioning. Combining artificial gravity through short-arm centrifugation with rowing exercise may serve as a countermeasure. We aimed to compare the tolerability, muscle force production, cardiovascular response, and power output of rowing on a short-arm centrifuge and under terrestrial gravity. Twelve rowing athletes (4 women, aged 27.2 ± 7.4 years, height 179 ± 0.1 cm, mass 73.7 ± 9.4 kg) participated in two rowing sessions, spaced at least six weeks apart. One session used a short-arm centrifuge with +0.5 Gz, while the other inclined the rowing ergometer by 26.6° to mimic centrifugal loading. Participants started self-paced rowing at 30 W, increasing by 15 W every three minutes until exhaustion. We measured rowing performance, heart rate, blood pressure, ground reaction forces, leg muscle activation, and blood lactate concentration. Rowing on the centrifuge was well-tolerated without adverse events. No significant differences in heart rate, blood pressure, or blood lactate concentration were observed between conditions. Inclined rowing under artificial gravity resulted in lower power output (−33%, p < 0.001) compared to natural gravity, but produced higher mean and peak ground reaction forces (p < 0.0001) and increased leg muscle activation. Muscle activation and ground reaction forces varied with rotational direction. Rowing in artificial gravity shows promise as a strategy against cardiovascular and muscular deconditioning during long-term spaceflight, but further investigation is required to understand its long-term effects.
Electric-field-induced crystallization of Hf0.5Zr0.5O2 thin film based on phase-field modeling
Authors: Liu Zhaobo , Shi Xiaoming , Wang Jing , Huang Houbing
Published: May 2024

Ferroelectricity in crystalline hafnium oxide has attracted considerable attention because of its potential application for memory devices. A recent breakthrough involves electric-field-induced crystallization, allowing HfO2-based materials to avoid high-temperature crystallization, which is unexpected in the back-end-of-line process. However, due to the lack of clarity in understanding the mechanisms during the crystallization process, we aim to employ theoretical methods for simulation, to guide experimental endeavors. In this work, we extended our phase-field model by coupling the crystallization model and time-dependent Ginzburg-Landau equation to analyze the crystalline properties and the polarization evolution of Hf0.5Zr0.5O2thin film under applying an electric field periodic pulse. Through this approach, we found a wake-up effect during the process of crystallization and a transformation from orthorhombic nano-domains to the stripe domain. Furthermore, we have proposed an innovative artificial neural synapse concept based on the continuous polarization variation under applied electric field pulses. Our research lays the theoretical groundwork for the advancement of electric-field-induced crystallization in the hafnium oxide system.
Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges
Authors: Warner Bryce M. , Yates Jacob G. E. , Vendramelli Robert , Truong Thang , Meilleur Courtney , Chan Lily , Leacy Alexander , Pham Phuc H. , Pei Yanlong , Susta Leonardo , Wootton Sarah K. , Kobasa Darwyn
Published: May 2024

The rapid development and deployment of vaccines following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions of lives. Despite their immense success, there remains a need for next-generation vaccination approaches for SARS-CoV-2 and future emerging coronaviruses and other respiratory viruses. Here we utilized a Newcastle Disease virus (NDV) vectored vaccine expressing the ancestral SARS-CoV-2 spike protein in a pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters and K18 mice against Delta and Omicron SARS-CoV-2 variants of concern. Additionally, intranasal vaccination induced robust, durable protection that was extended to 6 months post-vaccination. Overall, our data provide evidence that NDV-vectored vaccines represent a viable next-generation mucosal vaccination approach.
Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy
Authors: Julg Boris , Stephenson Kathryn E. , Tomaka Frank , Walsh Stephen R. , Sabrina Tan C. , Lavreys Ludo , Sarnecki Michal , Ansel Jessica L. , Kanjilal Diane G. , Jaegle Kate , Speidel Tessa , Nkolola Joseph P. , Borducchi Erica N. , Braams Esmee , Pattacini Laura , Burgess Eleanor , Ilan Shlomi , Bartsch Yannic , Yanosick Katherine E. , Seaman Michael S. , Stieh Daniel J. , van Duijn Janine , Willems Wouter , Robb Merlin L. , Michael Nelson L. , Walker Bruce D. , Pau Maria Grazia , Schuitemaker Hanneke , Barouch Dan H.
Published: May 2024

Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.