bluuebunny/crossref_metadata_2025 huggingface dataset:
Subsumption in Theatre
Authors: Bennett Michael Y
Published: March 2024

David Friedell has recently discussed the relationship between intrinsic and extrinsic properties of art, specifically in music. Friedell claims that normative social rules dictate who can change the intrinsic or extrinsic properties of a piece of music. This chapter claims that in text-based theatre—as a particular art form—the dividing line between intrinsic and extrinsic properties of a play is sometimes tenuous. This tenuousness is due to a play’s bifurcated existence as a dramatic text and as many theatrical performances. Moving from investigating the truth found in a play to thinking about a problematic character type, the chapter examines a problem case that the offstage character poses for conversations surrounding indeterminate identity. It examines indeterminate identity, not by asking whether two characters can be identical, but by claiming that it is indeterminate whether the offstage character, Godot, corresponds to multiple fictional entities.
Truthfulness in Theatre
Authors: Bennett Michael Y
Published: March 2024

Beginning by asking, “Who is Hamlet?” which is a question that has, for centuries, been asked and never fully (or satisfactorily) been definitively answered, what if, rather, we ask, “Who cannot be Hamlet?” By thinking about acting and the character through the concepts of subsumption and distinctness, this chapter creates a spectrum where “Who is Hamlet?” and “Who cannot  be Hamlet?” are the two poles that contain distinct properties. The chapter then examines uninvestigated spaces of theatrical stages that have not been experienced and/or do not exist, except in the imagination of, say, audience members. It is not just, for example, offstage characters that are caught in the crosshairs of the imagination of the different viewers; so, too, whether passively or actively, the empty spaces of the stage are often filled in more completely by imagination. Importantly, multiple viewers are all doing this, too.
Conclusion
Authors: Bennett Michael Y
Published: March 2024

This chapter concludes by thinking ethically—about value in, and the value of, theatre—by suggesting that because of the many empty conceptual spaces in theatre that both participating in and watching theatre require and encourage curious behaviors. In investigating what curiosity is and how theatre helps develop individually and societally needed curious behaviors, the chapter likens theatre to some games that are found in some well-known plays (e.g., card games, chess, etc.). It also creates ten logical expressions that explain theatre’s rules of engagement. Finally, until now, curiosity has mostly been seen as a mental process or drive. This chapter claims that curiosity refers to a cluster of different behaviors that are all loosely connected to the creation and/or acquisition of knowledge. By thinking about how the blank spaces of theatre require both participants and viewers to create and/or acquire knowledge, the chapter concludes by considering how theatre itself promotes curious behaviors.
High toxin concentration in pollen may deter collection by bees in butterfly-pollinated Rhododendron molle
Authors: Feng Hui-Hui , Lv Xiao-Wen , Yang Xiao-Chen , Huang Shuang-Quan
Published: March 2024

Backgrounds and Aims

The hypothesis that plants evolve features that protect accessible pollen from consumption by flower visitors remains poorly understood.

Methods

To explore potential chemical defence against pollen consumption, we examined the pollinator assemblage, foraging behaviour, visitation frequency and pollen transfer efficiency in Rhododendron molle, a highly toxic shrub containing rhodojaponin III. Nutrient (protein and lipid) and toxic components in pollen and other tissues were measured.

Key Results

Overall in the five populations studied, floral visits by butterflies and bumblebees were relatively more frequent than visits by honeybees. All foraged for nectar but not pollen. Butterflies did not differ from bumblebees in the amount of pollen removed per visit, but deposited more pollen per visit. Pollination experiments indicated that R. molle was self-compatible, but both fruit and seed production were pollen-limited. Our analysis indicated that the pollen was not protein-poor and had a higher concentration of the toxic compound rhodojaponin III than petals and leaves, this compound was undetectable in nectar.

Conclusion

Pollen toxicity in Rhododendron flowers may discourage pollen robbers (bees) from taking the freely accessible pollen grains, while the toxin-free nectar rewards effective pollinators, promoting pollen transfer. This preliminary study supports the hypothesis that chemical defence in pollen would be likely to evolve in species without physical protection from pollinivores.
Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice
Authors: Fang Miao , Yao Jie , Zhang Haifeng , Sun Jiahui , Yin Yiping , Shi Hongzhou , Jiang Guangqing , Shi Xin
Published: March 2024

The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress of gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. First, the characteristics of Mettl3 expression in inflammatory bowel diseases (IBD) patients were examined. Afterward, we generated the mice line with intestinal epithelial cells (IECs)-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc. between the two groups. Subsequently, we took advantage of staining assays to analyze mucosal damage and immune infiltration of Mettl3WT and Mettl3KO primary IECs. Bulk RNA sequencing was used to pursuit the differential expression of genes (DEGs) and associated signaling pathways after losing Mettl3. Pyroptosis-related proteins were to determine whether cell death was caused by pyroptosis. Eventually, CyTOF was performed to probe the difference of CD45+ cells, especially CD3e+ T-cell clusters after losing Mettl3. In IBD patients, Mettl3 was highly expressed in the inner-nucleus of IECs while significantly decreased upon acute intestinal inflammation. IECs-specific deletion of Mettl3 KO mice triggered a wasting phenotype and developed spontaneous colitis. The survival rate, body weight, and intestinal length observed from 2 to 8 weeks of Mettl3KO mice were significantly lower than Mettl3WT mice. The degree of mucosal damage and immune infiltration in Mettl3KO were even more serious than in their WT littermate. Bulk RNA sequencing demonstrated that DEGs were dramatically enriched in NOD-signaling pathways due to the loss of Mettl3. The colonic epithelium was more prone to pyroptosis after losing Mettl3. Subsequently, CyTOF revealed that T cells have altered significantly in Mettl3KO. Furthermore, there was abnormal proliferation of CD4+ T and markedly exhaustion of CD8 + T in Mettl3KO mice. In severe IBD patients, Mettl3 is located in the inner-nucleus of IECs and declined when intestinal inflammation occurs. Subsequently, Mettl3 prevented mice from developing colitis.
Endothelin receptor antagonists in diabetic and non-diabetic chronic kidney disease
Authors: Ivković Vanja , Bruchfeld Annette
Published: March 2024

Chronic kidney disease (CKD) is one of the major causes of morbidity and mortality, affecting >800 million persons globally. While we still lack efficient, targeted therapies addressing the major underlying pathophysiologic processes in CKD, findings of several recent trials have brought about a shifting landscape of promising therapies. The endothelin system has been implicated in the pathophysiology of CKD and endothelin receptor antagonists are one class of drugs for which we have increasing evidence of efficacy in these patients. In this review we summarize the most recent findings on the safety and efficacy of endothelin receptor antagonists in diabetic and non-diabetic CKD, future directions of research and upcoming treatments.
Stem cell factor and cKIT modulate endothelial glycolysis in hypoxia
Authors: Jeong Hayoung , Kim Ryul-I , Koo Hyunwoo , Choi Yang Hee , Kim Minju , Roh Hyejin , Park Sang Gyu , Sung Jong-Hyuk , Kim Koung Li , Suh Wonhee
Published: March 2024

Aims

In hypoxia, endothelial cells (ECs) proliferate, migrate, and form new vasculature in a process called angiogenesis. Recent studies have suggested that ECs rely on glycolysis to meet metabolic needs for angiogenesis in ischaemic tissues, and several studies have investigated the molecular mechanisms integrating angiogenesis and endothelial metabolism. Here, we investigated the role of stem cell factor (SCF) and its receptor, cKIT, in regulating endothelial glycolysis during hypoxia-driven angiogenesis.

Methods and results

SCF and cKIT signalling increased the glucose uptake, lactate production, and glycolysis in human ECs under hypoxia. Mechanistically, SCF and cKIT signalling enhanced the expression of genes encoding glucose transporter 1 (GLUT1) and glycolytic enzymes via Akt- and ERK1/2-dependent increased translation of hypoxia inducible factor 1A (HIF1A). In hypoxic conditions, reduction of glycolysis and HIF-1α expression using chemical inhibitors significantly reduced the SCF-induced in vitro angiogenesis in human ECs. Compared with normal mice, mice with oxygen-induced retinopathy (OIR), characterized by ischaemia-driven pathological retinal neovascularization, displayed increased levels of SCF, cKIT, HIF-1α, GLUT1, and glycolytic enzymes in the retina. Moreover, cKIT-positive neovessels in the retina of mice with OIR showed elevated expression of GLUT1 and glycolytic enzymes. Further, blocking SCF and cKIT signalling using anti-SCF neutralizing IgG and cKIT mutant mice significantly reduced the expression of HIF-1α, GLUT1, and glycolytic enzymes and decreased the pathological neovascularization in the retina of mice with OIR.

Conclusion

We demonstrated that SCF and cKIT signalling regulate angiogenesis by controlling endothelial glycolysis in hypoxia and elucidated the SCF/cKIT/HIF-1α axis as a novel metabolic regulation pathway during hypoxia-driven pathological angiogenesis.
Best practices for the manual curation of intrinsically disordered proteins in DisProt
Authors: Quaglia Federica , Chasapi Anastasia , Nugnes Maria Victoria , Aspromonte Maria Cristina , Leonardi Emanuela , Piovesan Damiano , Tosatto Silvio C E
Published: March 2024

The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure. Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt.

Database URL: https://disprot.org/
Histological Outcomes and JAK-STAT Signalling in Ulcerative Colitis Patients Treated with Tofacitinib
Authors: van Gennep Sara , Fung Ivan C N , Jong Djuna C de , Ramkisoen Rishand K , Clasquin Esmé , de Jong Jitteke , de Vries Leonie C S , de Jonge Wouter J , Gecse Krisztina B , Löwenberg Mark , Woolcott John C , Mookhoek Aart , D’Haens Geert R
Published: March 2024

Background and aims

Histological outcomes and JAK-STAT signalling were assessed in a prospective ulcerative colitis [UC] patient cohort after 8 weeks treatment with tofacitinib, an oral Janus kinase [JAK] inhibitor.

Methods

Forty UC patients received tofacitinib 10 mg twice daily for 8 weeks. Treatment response was defined as histo-endoscopic mucosal improvement [HEMI]. Histological remission was defined as a Robarts Histopathology Index [RHI] ≤3 points and histological response as 50% decrease in RHI. Mucosal expression of JAK1-3, tyrosine kinase 2 [TYK2], and total signal transducer and activator of transcription [STAT] 1-6 were assessed using immunohistochemistry [IHC].

Results

At baseline, the median RHI was 14 (interquartile range [IQR] 10–19). Of 40 [65%] patients, 26 had severe endoscopic disease [endoscopic Mayo score 3] and 31/40 [78%] failed prior anti-tumour necrosis factor [anti-TNF] treatment. At Week 8, 15 patients [38%] had HEMI, 23 patients [58%] histological remission, and 34 [85%] histological response. RHI decreased by a median of 14 points [IQR 9-21] in responders [p <0.001] and by 6 points [IQR 0-13] in non-responders [p = 0.002]. STAT1, STAT3, and STAT5 expression levels decreased significantly in the whole cohort. Responders had lower Week 8 STAT1 expression levels compared with non-responders [0.2%, IQR 0.1-2.8 vs 4.3%, IQR 1.2-11.9, p = 0.001], suggesting more profound STAT1 blockade. A trend of higher baseline JAK2 expression was observed in tofacitinib non-responders [2.7%, IQR 0.1-7.7] compared with responders [0.4%, IQR 0.1-2.1].

Conclusions

Tofacitinib treatment resulted in histological improvement in the majority of UC patients and in a substantial decrease of STAT1, STAT3, and STAT5 expression. HEMI was associated with more profound suppression of STAT1.
The challenge of advanced therapies in the contemporary era: first in Europe ECPELLA long-distance transfer—a case report
Authors: Fiorelli Francesca , Panoulas Vasileios , Riesgo Gil Fernando , Era Carl , Rosenberg Alexander
Published: March 2024

Background

The use of mechanical circulatory support (MCS) has markedly increased over the last decade, so have the inter-hospital transfers, with the aim of being able to offer advanced heart failure (AHF) therapies and centralizing patients to tertiary centres.

Case summary

In this article, we present the first in Europe long-distance air transfer of a patient supported by veno-arterial extracorporeal membrane oxygenator and Impella (ECPELLA), as a bridge to successful heart transplant. In our case report, a foreign young patient with AHF due to familiar cardiomyopathy required multiple MCS devices to achieve cardiovascular stability. After appropriate planning and multidisciplinary discussion, the patient was transferred on MCS to his country of origin via a fixed-wing airplane, in order to be assessed for heart transplantation. During take-off, the Impella flows temporarily dropped and a suction alarm was displayed; however, this rectified without intervention, and the rest of the flight was uneventful. One month after transfer, the patient underwent successful heart transplantation and remained clinically stable during the 12-month follow-up.

Discussion

Our experience links together the current challenges in the evolving AHF strategies and the increased need for inter-facility cooperation. Both these clinical and logistic challenges appear to lead to possible improved outcomes, after appropriate assessment, training, and accurate planning. Our experience provides useful information on feasibility of long-distance transport of patients supported by ECPELLA in Europe.
The evolution of the gliotoxin biosynthetic gene cluster in Penicillium fungi
Authors: Balamurugan Charu , Steenwyk Jacob L , Goldman Gustavo H , Rokas Antonis
Published: March 2024

Fungi biosynthesize diverse secondary metabolites, small organic bioactive molecules with key roles in fungal ecology. Fungal secondary metabolites are often encoded by physically clustered genes known as biosynthetic gene clusters (BGCs). Fungi in the genus Penicillium produce a cadre of secondary metabolites, some of which are useful (e.g. the antibiotic penicillin and the cholesterol-lowering drug mevastatin) and others harmful (e.g. the mycotoxin patulin and the immunosuppressant gliotoxin) to human affairs. Fungal genomes often also encode resistance genes that confer protection against toxic secondary metabolites. Some Penicillium species, such as Penicillium decumbens, are known to produce gliotoxin, a secondary metabolite with known immunosuppressant activity. To investigate the evolutionary conservation of homologs of the gliotoxin BGC and of genes involved in gliotoxin resistance in Penicillium, we analyzed 35 Penicillium genomes from 23 species. Homologous, lesser fragmented gliotoxin BGCs were found in 12 genomes, mostly fragmented remnants of the gliotoxin BGC were found in 21 genomes, whereas the remaining 2 Penicillium genomes lacked the gliotoxin BGC altogether. In contrast, broad conservation of homologs of resistance genes that reside outside the BGC across Penicillium genomes was observed. Evolutionary rate analysis revealed that BGCs with higher numbers of genes evolve slower than BGCs with few genes, suggestive of constraint and potential functional significance or more recent decay. Gene tree–species tree reconciliation analyses suggested that the history of homologs in the gliotoxin BGC across the genus Penicillium likely involved multiple duplications, losses, and horizontal gene transfers. Our analyses suggest that genes encoded in BGCs can have complex evolutionary histories and be retained in genomes long after the loss of secondary metabolite biosynthesis.
Genome Assembly and Annotation of the Dark-Branded Bushbrown Butterfly Mycalesis mineus (Nymphalidae: Satyrinae)
Authors: Murugesan Suriya Narayanan , Tian Shen , Monteiro Antónia
Published: March 2024

We report a high-quality genome draft assembly of the dark-branded bushbrown, Mycalesis mineus, a member of the Satyrinae subfamily of nymphalid butterflies. This species is emerging as a promising model organism for investigating the evolution and development of phenotypic plasticity. Using 45.99 Gb of long-read data (N50 = 11.11 kb), we assembled a genome size of 497.4 Mb for M. mineus. The assembly is highly contiguous and nearly complete (96.8% of Benchmarking Universal Single-Copy Orthologs lepidopteran genes were complete and single copy). The genome comprises 38.71% of repetitive elements and includes 20,967 predicted protein-coding genes. The assembled genome was super-scaffolded into 28 pseudo-chromosomes using a closely related species, Bicyclus anynana, with a chromosomal-level genome as a template. This valuable genomic tool will advance both ongoing and future research focused on this model organism.
Identification of CAF-related lncRNAs at the pan-cancer level represents a potential carcinogenic risk
Authors: Wang Mingwei , Jiang Minghui , Xie Aimin , Zhang Nan , Xu Yan
Published: March 2024

Cancer-associated fibroblasts (CAFs) are increasingly recognized as playing a crucial role in regulating cancer progression and metastasis. These cells can be activated by long non-coding RNAs (lncRNAs), promoting the malignant biological processes of tumor cells. Therefore, it is essential to understand the regulatory relationship between CAFs and lncRNAs in cancers. Here, we identified CAF-related lncRNAs at the pan-cancer level to systematically predict their potential regulatory functions. The identified lncRNAs were also validated using various external data at both tissue and cellular levels. This study has revealed that these CAF-related lncRNAs exhibit expression perturbations in cancers and are highly correlated with the infiltration of stromal cells, particularly fibroblasts and endothelial cells. By prioritizing a list of CAF-related lncRNAs, we can further distinguish patient subtypes that show survival and molecular differences. In addition, we have developed a web server, CAFLnc (https://46906u5t63.zicp.fun/CAFLnc/), to visualize our results. In conclusion, CAF-related lncRNAs hold great potential as a valuable resource for comprehending lncRNA functions and advancing the identification of biomarkers for cancer progression and therapeutic targets in cancer treatment.
Clinical Pharmacist Counselling Improves Long-term Medication Safety and Patient-reported Outcomes in Anti-TNF-treated Patients With Inflammatory Bowel Diseases: The Prospective, Randomized AdPhaNCED Trial
Authors: Plechschmidt Johannes , Fietkau Konstantin , Hepp Tobias , Dietrich Peter , Fischer Sarah , Krebs Sabine , Neurath Markus F , Dörje Frank , Atreya Raja
Published: March 2024

Background

Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients.

Methods

Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety.

Results

One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P < .001) and patient satisfaction with medication information (14.82 vs 11.60; P < .001) were significantly higher in the intervention group compared with the control group.

Conclusions

Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.
Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis
Authors: Jølving Line Riis , Zegers Floor Dijkstra , Lund Ken , Wod Mette , Nielsen Jan , Qvist Niels , Nielsen Rasmus Gaardskær , Nørgård Bente Mertz
Published: March 2024

Background

The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease (IBD). In early onset IBD, it may differ but the evidence is sparse. We aimed to investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis.

Methods

A register-based study included all Danish patients with early onset of IBD (≤18 years) between 1980 and 2021 and 50 matched references without IBD for each case. We examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis in Cox regression models.

Results

In total, 6822 patients with IBD were identified, and 337 728 matched references. The median age at the time of IBD diagnosis or index date for the matched references was 16 years (25-75 percentile: 13-18 years), and the median age at the time of an outcome or at the end of follow-up was 28.1 years (25-75 percentile: 21.5-37.0 years). According to the cumulative incidence plots psoriatic arthritis, and spondyloarthritis was diagnosed approximately 10 years after the IBD onset, and the remaining outcomes later. The adjusted hazard ratio after full follow-up was 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis, 5.21 (95% CI, 4.17-6.50) for spondyloarthritis, 2.77 (95% CI, 1.92-4.00) for celiac disease, 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis, 1.69 (95% CI, 1.23-2.32) and 1.64 (95% CI, 1.21-2.21) for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16 (95% CI, 0.97-1.40).

Conclusions

The risk estimates were significantly increased for all outcomes at the end of follow-up, except for thyroid disease, but according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.
Maximality Properties of Generalized Springer Representations of SO (N, ℂ)
Authors: La Ruben
Published: March 2024

Let $C$ be a unipotent class of $G=\textrm{SO}(N,\mathbb{C})$, $\mathcal{E}$ an irreducible $G$-equivariant local system on $C$. The generalized Springer representation $\rho (C,\mathcal{E})$ appears in the top cohomology of some variety. Let $\bar \rho (C,\mathcal{E})$ be the representation obtained by summing over all cohomology groups of this variety. It is well known that $\rho (C,\mathcal{E})$ appears in $\bar \rho (C,\mathcal{E})$ with multiplicity $1$ and that its Springer support $C$ is strictly minimal in the closure ordering among the Springer supports of the irreducbile subrepresentations of $\bar \rho (C,\mathcal{E})$. Suppose $C$ is parametrized by an orthogonal partition with only odd parts. We prove that $\bar \rho (C,\mathcal{E})$ (resp. $\textrm{sgn}\otimes \bar \rho (C,\mathcal{E})$) has a unique multiplicity 1 “maximal” subrepresentation $\rho ^{\textrm{max}}$ (resp. “minimal” subrepresentation $\textrm{sgn}\otimes \rho ^{\textrm{max}}$), where $\textrm{sgn}$ is the sign representation. These are analogues of results for $\textrm{Sp}(2n,\mathbb{C})$ by Waldspurger.
Animal models of eosinophilic esophagitis
Authors: Pilat Jennifer M , Jacobse Justin , Buendia Matthew A , Choksi Yash A
Published: March 2024

Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. Over the past 25 yr, great strides have been made toward understanding its pathogenesis, in part due to studies in several types of animal models. The vast majority of these models have been characterized in mice. In this review, we summarize the histopathological features of eosinophilic esophagitis recapitulated by these animal models, as well as discuss their strengths and weaknesses.
Diurnal activity in an insectivorous bat during migration period
Authors: Lučan Radek K , Bartonička Tomáš
Published: March 2024

Diurnal flight activity in otherwise strictly nocturnal bats has typically been linked to random disturbance from day roosts, an urgent need to balance food shortage caused by adverse weather during nighttime, or the absence of diurnal predators. However, migration may be another reason why bats fly during daylight, at least in some areas. Using community-science data collection, we obtained more than 500 records of over 15,000 bats displaying diurnal flight activity, suggesting that it is relatively common in Central Europe. The vast majority of sightings were of common noctules (Nyctalus noctula), with most records concentrated in spring and autumn. The seasonal dynamics of diurnal flights exactly coincided with migratory periods, and directional movements in autumn—when diurnal activity was most frequent and included highest numbers of observed bats—suggest that the behavior may ultimately be linked to migration ecology. The highest frequency of diurnal flights in autumn coincided with highest body mass in the studied territory, thereby refuting the hypothesis of early roost emergence due to poor body condition or decreased predation risk related to increased maneuverability. A shift from strictly nocturnal to partly diurnal activity may balance increased energetic demands imposed by migration, which is temporally synchronized with periods of cold nights when prey density is limited. Common noctule diurnal activity during the migratory period may be beneficial as they can acquire energy by foraging on daily abundant prey while saving nighttime for long endurance flights—alternatively, they may forage on the way to their migratory destination, thereby saving time. Predation risk from diurnal predators may be significantly decreased by choosing high flight altitudes, as observed particularly during autumn. We suggest that observations on the geographic distribution of diurnally flying noctules may help identify migration corridors.
Economic Principles for the Enforcement of Abuse of Dominance Provisions
Authors: Fumagalli Chiara , Motta Massimo
Published: March 2024

The European Commission (EC) has recently announced its intention to issue Guidelines on exclusionary abuses. In this paper, we explain how economics can and should be used to inform a sound and effects-based approach in the enforcement of Article 102 TFEU. In particular, the EC should be guided only by a consumer welfare standard; exclusive dealing and exclusivity rebates should be subject to a (rebuttable) presumption of harm; price–cost tests are meaningful only for predation and other practices that do not reference rivals; essentiality of the input should not be a requirement for vertical foreclosure cases of any type, but such cases should be limited only to dominant firms that satisfy certain criteria.
Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway
Authors: Yang Chunjing , Bao Li , Shi Zhengyuan , Xv Xiqiao , Jiang Dechun , You Longtai
Published: March 2024

Background

Phillyrin, the major lignin compound of Forsythia suspense (Thunb.) Vahl, has been shown the effects of anti-inflammatory and antioxidant. Our study was aimed to explore the protective effect of phillyrin on glomerular mesangial cells (HBZY-1) and the potential mechanism.

Methods

Cell viability, cytokine production, levels of reactive oxygen radicals (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as autophagy and apoptosis levels were determined to verify the mechanism of phillyrin on HBZY-1 cells.

Results

Our result indicated that phillyrin significantly inhibited HG-induced HBZY-1 proliferation by inhibiting Bcl-2 expression and upregulating Bad, cleaved caspase-3, and -9 expression. Also, phillyrin suppressed HG-induced mesangial extracellular matrix accumulation by inhibiting the expression of fibronectin and transforming growth factor-β1. Further, phillyrin inhibited oxidative stress and inflammation by decreasing ROS, MDA, TNF-α, IL-1β, and IL-6 contents and increasing SOD and GSH expression. Phillyrin also promoted autophagy by increasing LC3-II/LC3-I ratio and down-regulating p62 expression. Furthermore, WB assay showed that phillyrin inhibited oxidative stress caused by HG via activating Nrf2 signaling pathway, while attenuated proliferation and inflammation in HBZY-1 cells through inactivating PI3K/Akt/mTOR and NF-κB pathways.

Conclusion

All results showed that phillyrin might be a promising therapeutic agent for the treatment of DN.
Proximity ascertainment bias in early COVID case locations
Authors: Weissman Michael B
Published: March 2024

A comparison of the distances to the Huanan Seafood Market of early COVID cases with known links to the market versus cases without known links shows results apparently incompatible with a location model lacking proximity ascertainment bias. The sign of the difference instead agrees with a model in which such ascertainment bias is large. In the presence of such bias inferences based on the clustering of case locations become unreliable.
A non-zero Doppler amplitude is not enough: revisiting the putative radial velocity detection of sub-Venus exoplanet L 98-59b
Authors: Rajpaul Vinesh M , Barragán Oscar , Zicher Norbert
Published: March 2024

L 98-59b is a transiting exoplanet with radius ${0.85^{+0.061}_{-0.047}}$R⊕ and orbital period ${2.2531136^{+1.2e-06}_{-1.5e-06}}$ d. In 2021, a Doppler detection of  L 98-59b was announced, with radial velocity (RV) semi-amplitude $K_{\rm b}=0.46^{+0.20}_{-0.17}$$\textrm {m}\, \textrm {s}^{-1}$ inferred from 164 High Accuracy Radial velocity Planet Searcher and 66 Échelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observation RVs. This translated into a mass $M_{\rm b}=0.40^{+0.16}_{-0.15}$M⊕, or half the mass of Venus, making  L 98-59b then (by far) the lowest mass planet with a putative RV detection. To illuminate the difficulties in securely detecting <1 $\textrm {m}\, \textrm {s}^{-1}$ signals, we argue here that the published RV detection of  L 98-59b is not supported by sufficient statistical evidence. We show, under the published modelling assumptions, that Bayesian model comparison (BMC) suggests an $\sim 50~{{\ \rm per\ cent}}$ false-detection probability. We also often infer ∼40 $\textrm {cm}\, \textrm {s}^{-1}$ semi-amplitudes for Keplerians with periods not corresponding to any known planet; importantly, though, BMC rejects all these ‘detections’. By implementing a more sophisticated stellar activity model and more realistic parameter priors, we infer a mass Mb = 0.47 ± 0.14M⊕ from semi-amplitude Kb = 0.56 ± 0.16 $\textrm {m}\, \textrm {s}^{-1}$, with BMC now indicating substantial yet still not decisive evidence for the detection. Definitive detection and characterization may require many additional RVs, alongside careful modelling and stringent statistical analysis. Our case study has implications for current extreme-precision RV campaigns and the longer term quest to discover the first Earth-twins.
ALMA reveals a compact and massive molecular outflow driven by the young AGN in a nearby ULIRG
Authors: Holden Luke R , Tadhunter Clive , Audibert Anelise , Oosterloo Tom , Ramos Almeida Cristina , Morganti Raffaella , Pereira-Santaella Miguel , Lamperti Isabella
Published: March 2024

The ultraluminous infrared galaxy F13451+1232 is an excellent example of a galaxy merger in the early stages of active galactic nucleus (AGN) activity, a phase in which AGN-driven outflows are expected to be particularly important. However, previous observations have determined that the mass outflow rates of the warm ionized and neutral gas phases in F13451+1232 are relatively modest, and there has been no robust detection of molecular outflows. Using high-spatial resolution Atacama Large Millimeter/submillimeter Array CO(1–0) observations, we detect a kiloparsec-scale circumnuclear disc, as well as extended (r ∼ 440 pc), intermediate-velocity (300 < |v| < 400 km s−1) cold molecular gas emission that cannot be explained by rotational disc motions. If interpreted as AGN-driven outflows, the mass outflow rates associated with this intermediate-velocity gas are relatively modest ($\dot{M}_\mathrm{out}=22$–27 M⊙ yr−1); however, we also detect a compact (rout < 120 pc), high-velocity (400 < v < 680 km s−1) cold molecular outflow near the primary nucleus of F13451+1232, which carries an order of magnitude more mass ($\dot{M}_\mathrm{out}$ ∼ 230 M⊙ yr−1) than (and several times the kinetic power of) the previously detected warmer phases. Moreover, the similar spatial scales of this compact outflow and the radio structure indicate that it is likely accelerated by the small-scale (r ∼ 130 pc) AGN jet in the primary nucleus of F13451+1232. Considering the compactness of the nuclear outflow and intermediate-velocity non-rotating gas that we detect, we argue that high-spatial resolution observations are necessary to properly quantify the properties of AGN-driven outflows and their impacts on host galaxies.
William Shakespeare, The Tempest (1611)
Authors: Hadfield Andrew , Carvello Lesley
Published: March 2024

Shakespeare’s last single-authored play has an unusually complicated stage and critical history. Celebrated by many as a dramatic testament to the author’s own art, with Shakespeare representing himself as the magician Prospero, and possibly signaling his own retirement at the end of the play, it has also been a foundational text in postcolonial history, with the oppressed Caliban regarded as a colonized subject helpless to resist the aggressive appropriation of his island by Prospero, the failed and exiled Duke of Milan. Performances on stage and screen have, accordingly, varied significantly. Some emphasize the musical enchantment of the play, set on an island full of strange sounds and beautiful noises, culminating in a masque. Others, generally after the Second World War, emphasize the brutality of Prospero’s rule, casting the play as an allegory of colonial appropriation and power, the European invader dispossessing the native inhabitant. The Tempest has always been popular, and it was one of the most frequently performed of Shakespeare’s plays after the Restoration, adapted as an opera by William D’Avenant and John Dryden, with music by Henry Purcell, in 1674. It enjoyed attention throughout the eighteenth and nineteenth centuries, and continuing into the twentieth, when its critical and performance history started to shift with the advent of decolonization and the breakup of the European empires that had dominated much of the globe since Shakespeare’s time. The Tempest was one of the first of Shakespeare’s plays to be filmed, spawning both straightforward adaptations and more oblique versions. It has also appealed to a number of novelists and music writers. As a late Shakespeare play, it refuses easy generic classification, seeming to be an experimental work. The Tempest is carefully plotted in terms of the dramatic theory of the unities from Aristotle’s Poetics, obeying unity of time, a maximum of twenty-four hours; action, related and interconnected plots; and place, one location. Shakespeare’s play takes place over a day; all the plots are skillfully interwoven, from Prospero’s revenge against his brother to Stephano and Trinculo’s attempt to seize control of the island; and there is only one, confined location, the island after the storm. This unspecified Mediterranean island resembles a recently discovered American island, such as Bermuda, which was claimed for the Crown in 1612, a year after the play was first performed, and which had been the subject of recent discussion after the shipwreck of the Sea Venture there in 1609. Naming one of the play’s earlier—arguably indigenous—inhabitants, Caliban, further signals the cannibals, the ferocious man-eaters thought to populate the southern Americas and Caribbean islands. Moreover, the play’s significant deployment of music, with Prospero using music and sound to control people, has featured prominently in many critical works on the play.
Vulnerability, Intersectionality and Health in Migration
Authors: Osseiran Souad
Published: March 2024

Vulnerability and intersectionality are two lenses that have been relied on to explore specific themes relating to health in migration. Intersectionality, originally emerging in feminist and race studies, is relied on in scholarship on migration and migrant health due to the complex and overlapping factors influencing migrant experiences overall and health outcomes. Beyond philosophical discussions of vulnerability as situational or universal, vulnerability has been relied on in studies on the health of specific segments of society such as migrants or refugees. Vulnerability has been analyzed as increased risk of poor health due to migration, work conditions, and barriers to healthcare access among other factors. In much of the literature, vulnerability in migrant health is approached as arising due to work and living or other conditions, and it is understood as a heterogenous experience rather than it being a singular or uniform experience. Vulnerability in relation to migrant health has been explored as situational, structural, and group specific. While discussions on vulnerability may account for the intersecting dimensions of race, gender, and class and the impact of oppressive and exploitative relations, in many cases intersectionality theory specifically is not mentioned. Similarly, for research employing an intersectionality lens, vulnerability is mentioned in terms of increased likelihood of experiencing poor health or health inequities rather than as a theorizing of vulnerability. Vulnerability or intersectionality are then both used in research on health in migration, but with few resources engaging with both concepts simultaneously—highlighting possible avenues for further research. This entry will provide general overviews concerning vulnerability and intersectionality in migrant health and then focus on works utilizing either concept in the analysis of migrant health. In the following, the terms “migration” and “migrant” will be favored as encompassing terms that refer to multiple and diverse movements and legal statuses; based on the resource being annotated, “refugee” or “asylum seeker” may be used as relevant.
New occupational medicine competency framework for UK undergraduate medical students
Authors: Lalloo Drushca , Ryan Finola , Telling Wendy , Blackburn Laura , Peters Richard
Published: March 2024

Occupational medicine (OM) teaching is under-represented and inconsistent in UK medical school training. Unless universities take action, inadequate OM teaching provision will leave tomorrow’s doctors unprepared to support their patients to return to work after illness/injury, to remain at work and to identify occupational diseases. This Editorial presents a newly developed competency framework to assist universities to deliver OM education more consistently. This will support tomorrow’s doctors to achieve healthy working lives for their patients.
Navigating through the Reefs An Engaged Ethno-Archaeology Study of Torres Strait Islander Gidhal
Authors: Wright Duncan , Mitchell Rod , Repu Cygnet
Published: March 2024

For over a century Torres Strait Islander Elders’ accounts about the adventures of reforming ancestors have been recorded. The pathways of these muruygul integrate a chain of Torres Strait islands, neighboring Papua New Guinea, and northern Cape York Peninsula (Australia). According to Islanders, these narratives (each segment of which is owned by different communities) encode important information about cross-community cohesion in the past and present; a mythological geography commemorated through stories, songs, ceremonies, and art. In this chapter, Cygnet Repu describes the process by which he routinely “navigat[es] between the reefs” to “read” these multistage stories, using various cultural data sets. This method of detailed assessment of oral histories, archaeology, and language is applied herein to a gidha (important story, legend, myth) sequence relating to the wandering cultural heroes, Naga and Waiat (Wayath, called Waiet in Meriam Mìr, Waiati in Mawata-Daru Kiwai). We demonstrate how greater than 700-year-old story-line pathways taken by these cultural heroes are marked by transportation of loanwords and songs, artistic endeavors and ceremonial exchange. Excavation results are presented for community-wide celebrations and rites of passage associated with Waiat in Western and Eastern Torres Strait. Finally, we reassess past human activities within this region and the important role living saga traditions may play within broader understanding of saga histories and storytelling.
MORE FLORET1 controls anther development by negatively regulating key tapetal genes in both diploid and tetraploid rice
Authors: Lu Zijun , Zhu Lianjun , Liang Guobin , Li Xiaoxia , Li Qihang , Li Yajing , He Shengbo , Wu Jinwen , Liu Xiangdong , Zhang Jingyi
Published: March 2024

Polyploid hybrid rice (Oryza sativa) has great potential for increasing yields. However, hybrid rice depends on male fertility and its regulation, which is less well studied in polyploid rice than in diploid rice. We previously identified an MYB transcription factor, MORE FLORET1 (MOF1), whose mutation causes male sterility in neo-tetraploid rice. MOF1 expression in anthers peaks at anther Stage 7 (S7) and progressively decreases to low levels at S10. However, it remains unclear how the dynamics of MOF1 expression contribute to male fertility. Here, we carefully examined anther development in both diploid and tetraploid mof1 rice mutants, as well as lines ectopically expressing MOF1 in a temporal manner. MOF1 mutations caused delayed degeneration of the tapetum and middle layer of anthers and aberrant pollen wall organization. Ectopic MOF1 expression at later stages of anther development led to retarded cytoplasmic reorganization of tapetal cells. In both cases, pollen grains were aborted and seed production was abolished, indicating that precise control of MOF1 expression is essential for male reproduction. We demonstrated that 5 key tapetal genes, CYP703A3 (CYTOCHROME P450 HYDROXYLASE 703A3), OsABCG26 (O. sativa ATP BINDING CASSETTE G26), PTC1 (PERSISTENT TAPETAL CELL1), PKS2 (POLYKETIDE SYNTHASE 2), and OsABCG15 (O. sativa ATP BINDING CASSETTE G15), exhibit expression patterns opposite to those of MOF1 and are negatively regulated by MOF1. Moreover, DNA affinity purification sequencing (DAP-seq), luciferase activity assays, and electrophoretic mobility shift assays indicated that MOF1 binds directly to the PKS2 promoter for transcriptional repression. Our results provide a mechanistic basis for the regulation of male reproduction by MOF1 in both diploid and tetraploid rice. This study will facilitate the development of polyploid male sterile lines, which are useful for breeding of polyploid hybrid rice.
Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study
Authors: Kerola Anne M , Palomäki Antti , Laivuori Hannele , Laitinen Tarja , Färkkilä Martti , Eklund Kari K , Ripatti Samuli , Perola Markus , Ganna Andrea , Lindbohm Joni V , Mars Nina
Published: March 2024

Objectives

Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs).

Methods

Out of all of the 5 339 804 Finnish citizens, individuals born 1964–1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes.

Results

Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison’s disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1–1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis.

Conclusion

Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.