bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Damages on Modal Frequencies of Flat Glass Fiber Reinforced Polyurethane Foam Sandwich Structures
Authors: Rathika M. , Mahesh Kumar M. , Paul Vizhian S. , Gangadhar Shetty B. , Krishna M.
Published: May 2024

In this research work, experimental and numerical analyses were conducted to ascertain the impact of damages on modal frequencies of sandwich structure. The structure consists of laminated E/glass epoxy face sheets with [0°/90°]s stacking sequences and polyurethane foam core. The fabrication processes involved are hand layup technique, mold filling process and the use of adhesives to assemble the structure. Damages introduced during fabrication, encompassing core damage, delamination between face sheets and core and impact damage. Experimental modal testing was conducted on four distinct specimens using a Fast Fourier Transform (FFT) analyzer under cantilever boundary conditions. The results reveal significant variations in modal frequencies and mode shapes in the structures. A consistent six-mode frequency bandwidth is observed within the 2000 Hz range across all specimens. The numerical analysis was performed by Finite Element Method (FEM). Experimental and numerical results were in a good agreement. It was observed that modal frequencies decrease due to the presence of damage in the fabricated structures.
Analysis on a Battery Thermal Management System of an Lithium-Ion Powered Battery with Heat Sink for an Electric Vehicle
Authors: Rohini A , Abishek AS , Jeeva S
Published: May 2024

Electric vehicles (EVs) are changing the transportation business by giving an economical and sustainable option to the ecosystem in contrast to conventional vehicles with a sudden spike in demand for petroleum derivatives. The battery system that stores and disseminate electrical energy to the electric vehicles are basic to the outcome of EVs. Thermal management is basic for these batteries’ performance, safety and life span. This research article centres around the plan and examination of an EV-explicit Battery Thermal Management System (BTMS). To check the adverse consequences of high temperatures on battery cells, the BTMS integrates active and passive air-cooling strategies as well as different heat sink designs. The proposed BTMS further develops battery effectiveness, eliminate temperature-related risks and improves overall EV performance by maintaining appropriate thermal conditions. This study investigates the relevance of EV batteries, establishes defined objectives, gives numerical models and calculations, and conducts in-depth studies of various heat sink layouts. This research contributes to the growth of EV technology by empowering greener and cleaner transportation options while assuring the safety and efficiency of EV battery systems through careful examination and insightful analysis.
Energetic variational approaches for inviscid multiphase flow systems with surface flow and tension
Authors: Koba Hajime
Published: May 2024

We consider the governing equations for the motion of the inviscid fluids in two moving domains and an evolving surface from an energetic point of view. We employ our energetic variational approaches to derive inviscid multiphase flow systems with surface flow and tension. More precisely, we calculate the variation of the flow maps to the action integral for our model to derive both surface flow and tension. We also study the conservation and energy laws of our multiphase flow systems. The key idea of deriving the pressure of the compressible fluid on the surface is to make use of the feature of the barotropic fluid, and the key idea of deriving the pressure of the incompressible fluid on the surface is to apply a generalized Helmholtz-Weyl decomposition on a closed surface. In Appendix, we introduce one of the candidates for the viscous terms of viscous multiphase flow with a tangential compressible surface flow.
Stephen I, the First Christian King of Hungary
Authors: Berend Nora
Published: May 2024

This book questions the central importance of Stephen I of Hungary (reigned 997–1038) in narratives of Hungarian history and national identity as the founder of the Hungarian state and church. It argues that instead of conceptualizing modern political medievalism separately as an ‘abuse’ of history, we must investigate history’s very fabric, because cultural memory is woven into the production of the medieval sources. Medieval myth-making served as a firm basis for centuries of further elaboration and reinterpretation, both in historiography and in political legitimizing strategies. In many ways, we cannot reach the ‘real’ Stephen, but we can do much more to understand the shaping of his myths. The author traces the origin of crucial stories around Stephen, contextualizing both the invention of early narratives and their later use. A challenger to Stephen’s rule who may be a medieval literary invention became the protagonist of a rock opera in 1983, also standing in for Imre Nagy, a key figure of the 1956 revolution; moreover, he was reinvented as the embodiment of true Hungarian identity. The alleged right hand relic was ‘discovered’ to provide added legitimacy for Hungary’s kings and then became a protagonist of the entanglement of Church and state. A medieval crown was invested with supernatural status, before turning into a national symbol. This book analyses the often-seamless flow that has turned medieval myth into modern history, showing that politicization was not a modern addition, but a determinant factor from the start.
The Holy Dexter
Authors: Berend Nora
Published: May 2024

This chapter traces the invention of the relic of Stephen’s alleged right hand c. 1100, and its later uses. The relic has played a key role in ecclesiastical celebrations for centuries; in the twentieth century, it was also heavily politicized. As religious celebrations and grand state occasions were interconnected in the interwar period, in particular around St Stephen’s day, the Holy Dexter also became a reference point in politics. Conversely, during the communist period, the yearly religious procession was prohibited and the Holy Dexter itself was withdrawn from public display. Nobody has hitherto questioned the origin of the mummified hand; indeed, many scholars have expended considerable energy to prove that it truly is Stephen’s. However, because three saint’s lives were written about Stephen over the course of about twenty years in the late eleventh and early twelfth centuries, it is possible to follow the emergence of the story of the uncorrupted right hand, and also discover the likely models. The invention can be contextualized in the creation of the official Life of Stephen, which reflected the needs of the royal court at the time. The Holy Dexter heightened Stephen’s importance, as the holy founder came to be deployed in disputes with the papacy. The chapter also addresses the modern political uses of the relic, arising from the entanglement of the state and the Catholic Church.
The Grammar of Status Competition
Authors: Beaumont Paul David
Published: May 2024

A burgeoning body of research has documented that states of all kinds exert considerable energy and even blood and treasure seeking status on the world stage. Yet, for all scholars’ success in identifying instances of status seeking, they lack agreement on the nature of the international hierarchies states are said to compete within. The difficulty is twofold: international collective beliefs are unobservable, and there are a multitude of plausible ways to assess status in any given policy field or international context. The book addresses these puzzles head on by making a strength out of status’s widely acknowledged slipperiness. The book redirects inquiry away from unobservable international status hierarchies and onto the theories of international status (TIS) that governments and citizens produce and use to make sense of their state’s position in the world. Advancing a new theoretical framework for investigating how TIS inform policymaking, this book showcases its value via three case studies: how rival TIS were instrumental in legitimating (1) Norwegian education reforms at the turn of the 21st century; (2) the U.S. negotiating positions during the Strategic Arms Limitation Talks, and (3) the prosecution of Britain’s war with the Boer between 1899 and 1902. The book thereby provides answers to three major puzzles in international relations status research: why states compete for status when the international rewards seem ephemeral; how states can escape zero-sum competitions for status; and how status scholars can disentangle status from other motivations.
Rational Illusions
Authors: Beaumont Paul David
Published: May 2024

This chapter tackles head-on the puzzle of why states exert resources competing for international status when international recognition is seldom forthcoming and the gains from status are seemingly so ephemeral. To do so, it revisits a key case in IR’s status research: Britain’s tragic war with the Boer (1899–1902). The war has become a prime example of why the rewards from status-seeking are illusionary: the government treated victory as glorious even as the rest of the world remained unimpressed. Yet, by tracing the government’s evolving status theories across three episodes prior to, during, and after the Boer War, the chapter illuminates how, rather than resulting from psychological illusion that duped Britain’s leaders, the government’s status narrative is better described as a sociological and above all political construction that the government had considerable interest in fostering.
Symmetry over Strategy
Authors: Beaumont Paul David
Published: May 2024

Chapter 5 explores why the Strategic Arms Limitation Talks (SALT) proved so difficult to negotiate. The chapter addresses the long-standing puzzle in security studies: Why did the “superpowers” continue to arms-race even when a second-strike capability was assured? By tracing the official top-level security discourse via recently declassified archives, the chapter shows the negotiating positions United States took at SALT were primarily legitimated by theories of how domestic and international audiences would respond, rather than what was deemed necessary to deter the Soviets. Moreover, the chapter shows how the theory of status that was eventually settled upon was a downstream consequence of the domestic debate that followed SALT I. In this way, the rules defining international status solidified and crystallized during the process of SALT II, structuring the U.S. negotiating position, slowing down negotiations, and limiting U.S. ability to pursue other strategic objectives.
Effects of the combined exposure to chemicals and unusual working hours
Authors: Lie Jenny-Anne S , Zienolddiny-Narui Shan , Bråtveit Magne
Published: May 2024

Objective

Both exposure to occupational chemicals and to unusual working hours have well documented effects on health. Determination of occupational exposure limits is, however, usually based on chemical-only exposure and assumes an 8-h workday, 5 days/week and a 40-h work week. A significant proportion of the workforce is exposed to chemicals while working in other work schedules. This review thus aimed to synthesize and evaluate the scientific support for a combined effect of unusual working hours and chemical exposure and, if possible, give recommendations for OEL adjustments to account for unusual working hours.

Methods

The search for articles was made as part of the preparation of a report for the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. In this report, unusual working hours were categorized as shift work or extended (>8 h) working hours. Inclusion criteria were observational studies in the English language published up to November 2021 in peer-reviewed journals, with explicit metrics of exposure (chemicals and unusual working hours) and of health outcome, and which explicitly tested the association between exposure and outcome. Search engines of seven databases were used.

Results

Of the initially 15 400 identified papers, 9 studies published between 1985 and 2021 met the inclusion criteria, 7 of which showed significant associations. Results from a few of the studies, i.e. regarding effects of dust and endotoxin on lung function, effects of acetone on sleep quality and tiredness, effects of carbon disulphide on coronary artery disease and effects of chemicals on spontaneous abortion, suggested more pronounced effects during night shifts compared to during day shifts.

Discussion

The reviewed data is considered insufficient to conclude on recommendations for OEL adjustment for shift work. Suggested areas of future studies are mentioned.

Conclusion

Further studies about the effects of the combined exposure to unusual working hours and chemical exposure are essential for risk assessment, and for recommendation of potential OEL adjustments. What is important about this paper? Effects of chemical agents at the workplace may depend not only on exposure level and duration but also on the time of exposure in relation to the circadian rhythm. This study reviewed the scientific support for a combined effect of unusual working hours and chemical exposure and revealed an obvious need for additional studies regarding the complex interplay of the two different exposures with respect to adverse health effects.
Microscale marvels: unveiling the macroscopic significance of micropeptides in human health
Authors: Das Deepyaman , Podder Soumita
Published: May 2024

Non-coding RNA encodes micropeptides from small open reading frames located within the RNA. Interestingly, these micropeptides are involved in a variety of functions within the body. They are emerging as the resolving piece of the puzzle for complex biomolecular signaling pathways within the body. Recent studies highlight the pivotal role of small peptides in regulating important biological processes like DNA repair, gene expression, muscle regeneration, immune responses, etc. On the contrary, altered expression of micropeptides also plays a pivotal role in the progression of various diseases like cardiovascular diseases, neurological disorders and several types of cancer, including colorectal cancer, hepatocellular cancer, lung cancer, etc. This review delves into the dual impact of micropeptides on health and pathology, exploring their pivotal role in preserving normal physiological homeostasis and probing their involvement in the triggering and progression of diseases.
Molecular phylogenetics of Distephanus supports the recognition of a new tribe, Distephaneae (Asteraceae)
Authors: Gostel M R , Loeuille Benoit , Santana Mariana Henriques , Kelloff Carol L , Chan Raymund , Giraldes Simões Ana Rita , Larridon Isabel , Funk Vicki A
Published: May 2024

Distephanus Cass. comprises 43 distinctive species of shrubs and small trees that have been placed historically within the ironweed tribe, Vernonieae (Asteraceae). Using the most expansive sampling of Distephanus to date, this study aims to test the monophyly of this genus and facilitate its classification. Molecular phylogenetic analyses were conducted using four molecular markers from the nuclear and plastid genomes. These data also supported divergence dating analyses that were performed to understand the timing of diversification events within Distephanus and other related genera as well as ancestral area reconstruction analyses to infer the biogegraphic history of species diversity in this group. Results from this study indicate that, as currently circumscribed, Vernonieae is not monophyletic and that Distephanus is, in fact, sister to a clade that comprises Vernonieae and another tribe, Moquinieae, which only includes two species restricted to Brazil. On the basis of these findings, Distephanus is classified in a new tribe that we describe here, Distephaneae. This new tribe comprises 41 species of Distephanus that are easily distinguished from Moquinieae and Vernonieae based on the presence of florets with yellow corollas and trinervate leaves.
Distinct neural markers of evidence accumulation index metacognitive processing before and after simple visual decisions
Authors: Stone Caleb , Mattingley Jason B , Bode Stefan , Rangelov Dragan
Published: May 2024

Perceptual decision-making is affected by uncertainty arising from the reliability of incoming sensory evidence (perceptual uncertainty) and the categorization of that evidence relative to a choice boundary (categorical uncertainty). Here, we investigated how these factors impact the temporal dynamics of evidence processing during decision-making and subsequent metacognitive judgments. Participants performed a motion discrimination task while electroencephalography was recorded. We manipulated perceptual uncertainty by varying motion coherence, and categorical uncertainty by varying the angular offset of motion signals relative to a criterion. After each trial, participants rated their desire to change their mind. High uncertainty impaired perceptual and metacognitive judgments and reduced the amplitude of the centro-parietal positivity, a neural marker of evidence accumulation. Coherence and offset affected the centro-parietal positivity at different time points, suggesting that perceptual and categorical uncertainty affect decision-making in sequential stages. Moreover, the centro-parietal positivity predicted participants’ metacognitive judgments: larger predecisional centro-parietal positivity amplitude was associated with less desire to change one’s mind, whereas larger postdecisional centro-parietal positivity amplitude was associated with greater desire to change one’s mind, but only following errors. These findings reveal a dissociation between predecisional and postdecisional evidence processing, suggesting that the CPP tracks potentially distinct cognitive processes before and after a decision.
Transfer hydrogenation of aldehydes and ketones with tetrahydroxydiboran in water by an amphiphilic resin-supported nano-palladium catalyst
Authors: Zhang Kaili , Okumura Shintaro , Uozumi Yasuhiro
Published: May 2024

We have developed a transfer hydrogenation of aldehydes and ketones with B2(OH)4 as a reductant and amphiphilic resin-dispersed palladium nanoparticles as a catalyst system in an aqueous medium, where water also serves as a hydrogen donor. A variety of aldehydes and ketones, including aliphatic carbonyl compounds, reacted to give the corresponding primary and secondary alcohols, respectively. The catalyst was recovered by filtration and reused 9 times without a significant loss of its catalytic activity.
Safety Data Timelines for Pregnant Individuals With HIV on Antiretroviral Therapy
Authors: Short William R , Zimmerman Matty M , Mohamed Ola , Mofenson Lynne M
Published: May 2024

Antiretrovirals are often approved by the Food and Drug Administration without sufficient safety data regarding their use in pregnancy. To quantify this delay, we calculated the interval from the approval date to their inclusion in the Antiretroviral Pregnancy Registry prospective analysis (≥200 first-trimester exposures); the median delay was 6 years.
Spontaneous coronary artery dissection: a difficult journey from emergency coronary artery bypass grafting to left ventricular assist device
Authors: Ho Daniel , Alfaris Ibrahim , Joury Abdulaziz , Cecere Renzo , Giannetti Nadia
Published: May 2024

Background

Excluding spontaneous coronary artery dissection (SCAD) as an aetiology of acute coronary syndrome in young adults is imperative.

Case summary

A previously healthy 39-year-old woman experienced sudden severe chest pain, ST-segment elevation on electrocardiogram, necessitating high-dose aspirin and urgent transfer to a revascularization centre. Suffering ventricular tachycardia (VT) and ventricular fibrillation (VF), she underwent two rounds of advanced life support and venoarterial extracorporeal membrane oxygenation. Diagnosed with left main coronary artery (LMCA) SCAD, she was initially started on conservative therapy for declining left ventricular ejection fraction. However, she continued to experience an escalating anginal symptoms, worsening biomarkers, and LMCA SCAD progression, which urged the need for surgical intervention with coronary artery bypass graft surgery (CABG). Following her CABG, she experienced a worsening of her functional mitral regurgitating, which she underwent transcatheter edge-to-edge repair of her severe mitral regurgitation. Despite being listed for orthotopic heart transplantation (OHTx), her low body mass index and elevated antibodies necessitated the HeartMate III left ventricular assist device (LVAD) for bridge to transplant. After treating frequent VT episodes with medications, she eventually received a LVAD as a bridge to cardiac transplantation. Within 1 year of her receiving LVAD, she underwent a successful OHTx.

Discussion

The pathogenesis of SCAD involves intramural haematoma formation through intimal tears or vasa vasorum haemorrhage. Adverse outcomes that could occur in SCAD patients include cardiac arrest, cardiogenic shock, reduced left ventricle systolic function, and occasionally serious cardiac arrhythmia—such as VF—which can lead to sudden cardiac death. Although most SCAD cases heal spontaneously, revascularization can be considered in case of worsening SCAD progression. Advanced therapeutic intervention including mechanical circulatory support and OHTx should be considered in refractory cases.
Functional genomics reveals functions of terpene synthases for volatile terpene formation in peach
Authors: Wei Chunyan , Yang Huizhen , Li Rongrong , Su Yike , Li Xinzhao , Zhang Bo
Published: May 2024

Objectives

Terpenes are important volatile organic compounds that impact fruit aroma and flavor quality. Terpene synthases (TPSs) are the key enzymes responsible for the biosynthesis of basic backbone structure of terpenes. The identification and characterization of TPSs are critical for comprehending the biosynthesis of terpenes in fruit.

Materials and Methods

The present study utilized cultivated peach (Prunus persica L. Batsch) as materials. RNA-sequencing was employed to investigate the expression profiles of PpTPSs during fruit ripening and in response to hormone and temperature treatments. Enzyme activities of PpTPSs were assessed using different substrates.

Results

Here, we show that peach contains 38 TPS genes, with 24 members in the TPS-a cluster. Transcriptome analysis revealed that the expression of PpTPSs in peach fruits was regulated by environmental factors such as UV-B light and low temperature, as well as by phytohormones such as ethylene and methyl jasmonate. After analyzing the expression of 38 PpTPSs in peach fruit developmental stages and different tissues, we screened and cloned six new highly expressed TPS genes. Subcellular localization showed that PpTPS13 and PpTPS23 were localized in the plastid, whereas PpTPS12, PpTPS22, PpTPS25, and PpTPS28 were localized in the cytoplasm. Heterologous expression of PpTPSs in Escherichia coli followed by the enzymatic assays revealed that only four TPSs (PpTPS12, PpTPS22, PpTPS25, and PpTPS28) were active in vitro. Using GPP and FPP as substrates, these PpTPSs were able to synthesize an array of volatile terpenes, including 15 monoterpenes such as geraniol, camphene, pinene, borneol and phellandrene, and 14 sesquiterpenes such as farnesene, nerolidol and α-bergamotene.

Conclusions

Our results identify target genes for engineering to increase the production of volatile terpenes and thereby improve fruit quality.
The pattern of genetic variability in a core collection of 2,021 cowpea accessions
Authors: Fiscus Christopher J , Herniter Ira A , Tchamba Marimagne , Paliwal Rajneesh , Muñoz-Amatriaín María , Roberts Philip A , Abberton Michael , Alaba Oluwafemi , Close Timothy J , Oyatomi Olaniyi , Koenig Daniel
Published: May 2024

Cowpea is a highly drought-adapted leguminous crop with great promise for improving agricultural sustainability and food security. Here, we report analyses derived from array-based genotyping of 2,021 accessions constituting a core subset of the world's largest cowpea collection, held at the International Institute of Tropical Agriculture (IITA) in Ibadan, Nigeria. We used this dataset to examine genetic variation and population structure in worldwide cowpea. We confirm that the primary pattern of population structure is two geographically defined subpopulations originating in West and East Africa, respectively, and that population structure is associated with shifts in phenotypic distribution. Furthermore, we establish the cowpea core collection as a resource for genome-wide association studies by mapping the genetic basis of several phenotypes, with a focus on seed coat pigmentation patterning and color. We anticipate that the genotyped IITA Cowpea Core Collection will serve as a powerful tool for mapping complex traits, facilitating the acceleration of breeding programs to enhance the resilience of this crop in the face of rapid global climate change.
Relational Solidarity and Conflicting Ethics in Dementia Care in Urban India
Authors: Brijnath Bianca , Rao Rachita , Baruah Upasana , Antoniades Josefine , Loganathan Santosh , Varghese Mathew , Cooper Claudia , Kent Mike , Dow Briony
Published: May 2024

Objectives

Using the concept of relational solidarity, we examine how autonomy, equality, dignity, and personhood are practiced in the care of people living with dementia at home in urban India.

Methods

Video interviews with 19 family carers and 25 health providers conducted in English, Hindi, and Kannada in Bengaluru between March and July 2022. Data were translated into English and thematically analyzed.

Results

Family carers and providers unanimously agreed that people with dementia should be respected and cared for. Concurrently, they perceived people with dementia as being “like a kid” and used the analogy of a parent–child relationship to understand their care responsibilities. This analogy informed how ethical principles such as personhood and equality were reframed in the relationships between family carers and people with dementia, as well as how carers and providers maintained the safety but undermined the autonomy of people with dementia through restricting their movements inside and outside the home.

Discussion

There can be relational solidarity in dementia care at home in urban India but also contradictions in the interpretations and applications of the ethical principles of autonomy, equality, dignity, and personhood. As such, a more organic, grassroots model of ethical practice is needed to frame care and provide material support to families in India.
Clinical outcomes in patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection
Authors: Mourad Ahmad , Smith Alison G , Troy Jesse D , Holland Thomas L , Wrenn Rebekah H , Turner Nicholas A
Published: May 2024

Background

A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates.

Objectives

We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic.

Methods

We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups.

Results

Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5–71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0–16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30–1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%.

Conclusions

These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.
Enantiomer-specific analysis of amphetamine in urine, oral fluid and blood
Authors: Bakke Eirin , Nilsen Terland Mariann , Strand Dag Helge , Øiestad Elisabeth Leere , Høiseth Gudrun
Published: May 2024

Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.
SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 13 (SPL13) together with SPL9 redundantly regulates wax biosynthesis under drought stress
Authors: Huang Haodong , Zheng Minglü , Jenks Matthew A , Yang Pingfang , Zhao Huayan , Lü Shiyou
Published: May 2024

Wax biosynthesis is closely controlled by many regulators under different environmental conditions. We have previously shown that the module miR156–SQUAMOSA PROMOTER BINDING PROTEIN-LIKE9 (SPL9)–DEWAX is involved in the diurnal regulation of wax production; however, it was not determined whether other SPLs are also involved in wax synthesis. Here, we report that SPL13 also regulates drought-induced wax production, by directly and indirectly affecting the expression of the two wax biosynthesis genes ECERIFERUM1 (CER1) and CER4, respectively. In addition, we show that SPL13 together with SPL9 redundantly regulates wax accumulation under both normal and drought stress conditions, and that simultaneous mutation of both genes additively increases cuticle permeability and decreases drought tolerance. However, in contrast to SPL9, SPL13 does not seem to participate in the DEWAX-mediated diurnal regulation of wax production.
Genetic Causes and Genomic Consequences of Breakdown of Distyly in Linum trigynum
Authors: Gutiérrez-Valencia Juanita , Zervakis Panagiotis-Ioannis , Postel Zoé , Fracassetti Marco , Losvik Aleksandra , Mehrabi Sara , Bunikis Ignas , Soler Lucile , Hughes P William , Désamoré Aurélie , Laenen Benjamin , Abdelaziz Mohamed , Pettersson Olga Vinnere , Arroyo Juan , Slotte Tanja
Published: May 2024

Distyly is an iconic floral polymorphism governed by a supergene, which promotes efficient pollen transfer and outcrossing through reciprocal differences in the position of sexual organs in flowers, often coupled with heteromorphic self-incompatibility. Distyly has evolved convergently in multiple flowering plant lineages, but has also broken down repeatedly, often resulting in homostylous, self-compatible populations with elevated rates of self-fertilization. Here, we aimed to study the genetic causes and genomic consequences of the shift to homostyly in Linum trigynum, which is closely related to distylous Linum tenue. Building on a high-quality genome assembly, we show that L. trigynum harbors a genomic region homologous to the dominant haplotype of the distyly supergene conferring long stamens and short styles in L. tenue, suggesting that loss of distyly first occurred in a short-styled individual. In contrast to homostylous Primula and Fagopyrum, L. trigynum harbors no fixed loss-of-function mutations in coding sequences of S-linked distyly candidate genes. Instead, floral gene expression analyses and controlled crosses suggest that mutations downregulating the S-linked LtWDR-44 candidate gene for male self-incompatibility and/or anther height could underlie homostyly and self-compatibility in L. trigynum. Population genomic analyses of 224 whole-genome sequences further demonstrate that L. trigynum is highly self-fertilizing, exhibits significantly lower genetic diversity genome-wide, and is experiencing relaxed purifying selection and less frequent positive selection on nonsynonymous mutations relative to L. tenue. Our analyses shed light on the loss of distyly in L. trigynum, and advance our understanding of a common evolutionary transition in flowering plants.
PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells
Authors: Vijayakumar Anitha , Majumder Mrinmoyee , Yin Shasha , Brobbey Charles , Karam Joseph , Howley Breege , Howe Philip H , Berto Stefano , Madan Lalima K , Gan Wenjian , Palanisamy Viswanathan
Published: May 2024

Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1’s nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures. Disruption of G4-RNA structures by lithium chloride failed to bind with FXR1, indicating its preference for G4-RNA structure containing mRNAs. Furthermore, loss-of-function of PRMT5 inhibited FXR1 methylation both in vivo and in vitro, affecting FXR1 protein stability, inhibiting RNA-binding activity and cancer cell growth and proliferation. Finally, the enhanced crosslinking and immunoprecipitation (eCLIP) analyses reveal that FXR1 binds with the G4-enriched mRNA targets such as AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1 and UBR4 and controls its mRNA expression in cancer cells. Our findings suggest that PRMT5-mediated FXR1 methylation is required for RNA/G4-RNA binding, which promotes gene expression in cancer cells. Thus, FXR1’s structural characteristics and affinity for RNAs preferentially G4 regions provide new insights into the molecular mechanism of FXR1 in oral cancer cells.
LipidSig 2.0: integrating lipid characteristic insights into advanced lipidomics data analysis
Authors: Liu Chia-Hsin , Shen Pei-Chun , Lin Wen-Jen , Liu Hsiu-Cheng , Tsai Meng-Hsin , Huang Tzu-Ya , Chen I-Chieh , Lai Yo-Liang , Wang Yu-De , Hung Mien-Chie , Cheng Wei-Chung
Published: May 2024

In the field of lipidomics, where the complexity of lipid structures and functions presents significant analytical challenges, LipidSig stands out as the first web-based platform providing integrated, comprehensive analysis for efficient data mining of lipidomic datasets. The upgraded LipidSig 2.0 (https://lipidsig.bioinfomics.org/) simplifies the process and empowers researchers to decipher the complex nature of lipids and link lipidomic data to specific characteristics and biological contexts. This tool markedly enhances the efficiency and depth of lipidomic research by autonomously identifying lipid species and assigning 29 comprehensive characteristics upon data entry. LipidSig 2.0 accommodates 24 data processing methods, streamlining diverse lipidomic datasets. The tool's expertise in automating intricate analytical processes, including data preprocessing, lipid ID annotation, differential expression, enrichment analysis, and network analysis, allows researchers to profoundly investigate lipid properties and their biological implications. Additional innovative features, such as the ‘Network’ function, offer a system biology perspective on lipid interactions, and the ‘Multiple Group’ analysis aids in examining complex experimental designs. With its comprehensive suite of features for analyzing and visualizing lipid properties, LipidSig 2.0 positions itself as an indispensable tool for advanced lipidomics research, paving the way for new insights into the role of lipids in cellular processes and disease development.
SCTC: inference of developmental potential from single-cell transcriptional complexity
Authors: Lin Hai , Hu Huan , Feng Zhen , Xu Fei , Lyu Jie , Li Xiang , Liu Liyu , Yang Gen , Shuai Jianwei
Published: May 2024

Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.
IsoVis – a webserver for visualization and annotation of alternative RNA isoforms
Authors: Wan Ching Yin , Davis Jack , Chauhan Manveer , Gleeson Josie , Prawer Yair D J , De Paoli-Iseppi Ricardo , Wells Christine A , Choi Jarny , Clark Michael B
Published: May 2024

Genes commonly express multiple RNA products (RNA isoforms), which differ in exonic content and can have different functions. Making sense of the plethora of known and novel RNA isoforms being identified by transcriptomic approaches requires a user-friendly way to visualize gene isoforms and how they differ in exonic content, expression levels and potential functions. Here we introduce IsoVis, a freely available webserver that accepts user-supplied transcriptomic data and visualizes the expressed isoforms in a clear, intuitive manner. IsoVis contains numerous features, including the ability to visualize all RNA isoforms of a gene and their expression levels; the annotation of known isoforms from external databases; mapping of protein domains and features to exons, allowing changes to protein sequence and function between isoforms to be established; and extensive species compatibility. Datasets visualised on IsoVis remain private to the user, allowing analysis of sensitive data. IsoVis visualisations can be downloaded to create publication-ready figures. The IsoVis webserver enables researchers to perform isoform analyses without requiring programming skills, is free to use, and available at https://isomix.org/isovis/.
A bisulfite-assisted and ligation-based qPCR amplification technology for locus-specific pseudouridine detection at base resolution
Authors: Fang Xin , Zhao Ruiqi , Wang Yafen , Sun Mei , Xu Jin , Long Shengrong , Mo Jing , Liu Hudan , Li Xiang , Wang Fang , Zhou Xiang , Weng Xiaocheng
Published: May 2024

Over 150 types of chemical modifications have been identified in RNA to date, with pseudouridine (Ψ) being one of the most prevalent modifications in RNA. Ψ plays vital roles in various biological processes, and precise, base-resolution detection methods are fundamental for deep analysis of its distribution and function. In this study, we introduced a novel base-resolution Ψ detection method named pseU-TRACE. pseU-TRACE relied on the fact that RNA containing Ψ underwent a base deletion after treatment of bisulfite (BS) during reverse transcription, which enabled efficient ligation of two probes complementary to the cDNA sequence on either side of the Ψ site and successful amplification in subsequent real-time quantitative PCR (qPCR), thereby achieving selective and accurate Ψ detection. Our method accurately and sensitively detected several known Ψ sites in 28S, 18S, 5.8S, and even mRNA. Moreover, pseU-TRACE could be employed to measure the Ψ fraction in RNA and explore the Ψ metabolism of different pseudouridine synthases (PUSs), providing valuable insights into the function of Ψ. Overall, pseU-TRACE represents a reliable, time-efficient and sensitive Ψ detection method.
Identifying Ultrahigh-Temperature Metamorphism in Basic Granulites
Authors: Wang Bin , Wei Chunjing
Published: May 2024

Identifying ultrahigh-temperature (UHT) metamorphism in basic granulites is challenged by the uncertainty of peak temperatures. Consequently, available temperature indicators are desiderated all along. In this study, we investigated low-pressure basic granulites from the Daqingshan, North China Craton and determined a UHT peak condition around 1000–1050 °C and 0.8–0.9 GPa. This peak condition was constrained by combining the AlT of 0.10–0.12 in clinopyroxene (Cpx) cores, maximum Ti of 0.36–0.38 in amphibole (Amp) cores and anorthite proportion (XAn) of 0.67–0.70 and 0.61–0.63 in plagioclase (Pl) cores/mantles analyzed in two selected samples. The P–T records obtained from several thermobarometers related to amphibole, plagioclase and/or clinopyroxene were also verified to be in agreement with the phase equilibria modeling results. Notably, AlT-in-Cpx is assessed to be a reliable temperature indicator in basic granulites with the Opx–Cpx–Pl–Amp assemblage, albeit could be influenced by bulk-rock compositions in some extent and has a temperature standard error of ~70 °C. Besides, the post-peak evolution was dominated by near-isobaric cooling at 1.94–1.93 Ga, to a fluid-absent solidus as high as ~940 °C. During the cooling process, plagioclase and amphibole grew together at the expense of Al-rich clinopyroxene and unsegregated melts, accompanied by the (rimward) decrease of AlT-in-Cpx, Ti-in-Amp and XAn-in-Pl. A pre-peak process is inferred to be decompressional heating. The UHT metamorphism in Daqingshan is interpreted to result from asthenosphere upwelling and thermal advection from regional mantle-derived magmatism during post-orogenic extension, in a newly developed back-arc-related environment.
Chloroplast biogenesis involves spatial coordination of nuclear and organellar gene expression in Chlamydomonas
Authors: Sun Yi , Bakhtiari Shiva , Valente-Paterno Melissa , Wu Yanxia , Nishimura Yoshiki , Shen Weike , Law Christopher , Dhaliwal James , Dai Daniel , Bui Khanh Huy , Zerges William
Published: May 2024

The localization of translation can direct the polypeptide product to the proper intracellular compartment. Our results reveal translation by cytosolic ribosomes on a domain of the chloroplast envelope in the unicellular green alga Chlamydomonas (Chlamydomonas reinhardtii). We show that this envelope domain of isolated chloroplasts retains translationally active ribosomes and mRNAs encoding chloroplast proteins. This domain is aligned with localized translation by chloroplast ribosomes in the translation zone, a chloroplast compartment where photosystem subunits encoded by the plastid genome are synthesized and assembled. Roles of localized translation in directing newly synthesized subunits of photosynthesis complexes to discrete regions within the chloroplast for their assembly are suggested by differences in localization on the chloroplast of mRNAs encoding either subunit of the light-harvesting complex II or the small subunit of Rubisco. Transcription of the chloroplast genome is spatially coordinated with translation, as revealed by our demonstration of a subpopulation of transcriptionally active chloroplast nucleoids at the translation zone. We propose that the expression of chloroplast proteins by the nuclear-cytosolic and organellar genetic systems is organized in spatially aligned subcompartments of the cytoplasm and chloroplast to facilitate the biogenesis of the photosynthetic complexes.
Nanobody-based CAR NK cells for possible immunotherapy of MICA+ tumors
Authors: Verhaar Elisha R , van Keizerswaard Willemijn J C , Knoflook Anouk , Balligand Thomas , Ploegh Hidde L
Published: May 2024

The glycoproteins MICA and MICB are upregulated on the surface of cells undergoing stress, for instance due to (viral) infection or malignant transformation. MICA/B are the ligands for the activating receptor NKG2D, found on cytotoxic immune cells like NK cells, CD8+ T cells, and γδ T cells. Upon engagement of NKG2D, these cells are activated to eradicate the MICA/B-positive targets, assisted by the secretion of cytokines. Nanobodies, or VHHs, are derived from the variable regions of camelid heavy-chain only immunoglobulins. Nanobodies are characterized by their small size, ease of production, stability, and specificity of recognition. We generated nanobodies that recognize membrane-bound MICA with high affinity. Here, we use these nanobodies as building blocks for a chimeric antigen receptor (CAR) to establish VHH-based CAR NK cells. These anti-MICA nanobody-based CAR NK cells recognize and selectively kill MICA-positive tumor cells in vitro and in vivo. We track localization of the VHH-based CAR NK cells to MICA-positive lung metastases by immuno-positron emission tomography imaging.