bluuebunny/crossref_metadata_2025 huggingface dataset:
Die paradoxe Wirkung von Altersbildern auf das Alters- und Gesundheitserleben älterer Menschen – Befunde einer quantitativen und qualitativen Studienreihe
Authors: Wangler Julian , Jansky Michael
Published: June 2023

Hintergrund

Öffentlich zirkulierende Altersbilder spielen eine zentrale Rolle für Verhaltenszuschreibungen in Bezug auf ältere Menschen sowie die individuelle Wahrnehmung des Alterungsprozesses. Bislang fehlt es an Erkenntnissen, inwieweit Altersbilder sich auf das Alters- und Gesundheitserleben sowie Selbstkonzepte älterer Menschen auswirken können.

Ziel der Arbeit

Die Studienreihe hat ältere Proband*innen kontrolliert mit prototypischen medialen Altersdarstellungen konfrontiert. Es wurden Auswirkungen auf Einstellungen zum Alter und persönliches Älterwerden ermittelt. Von Interesse war, inwiefern die Konfrontation mit dem Stimulusmaterial Auswirkungen auf das Empfinden von Älterwerden, Gesundheit und Körperlichkeit zeigt.

Material und Methoden

Aufbauend auf einer inhaltsanalytischen Vorstudie wurden im Jahr 2020 insgesamt 910 Proband*innen ab 60 Jahre im Rahmen einer quasiexperimentellen Befragung mit unterschiedlichen Altersframes konfrontiert. Ergänzend wurden im Jahr 2022 insgesamt 36 fokussierte Interviews mit älteren Menschen geführt, denen jeweils ein Stimulus in Form eines Artikels vorgelegt wurde, der Alter und Älterwerden in spezifischer Weise präsentiert.

Ergebnisse

Die Ergebnisse belegen, dass die Rezeption eines negativen Altersframes zu einer Verbesserung des Selbstbildes älterer Menschen führt. Die Rezeption des positiven Altersframes führt hingegen zu einer Verschlechterung des Selbstbildes. Im Zuge der Interviews wurde deutlich, dass die Konfrontation mit einer positiv überhöhten Altersdarstellung bei den Befragten zu Unsicherheit, Stress und Selbstzweifeln führte. Die Hälfte der Befragten stellte fest, die Anforderungen an ein „modernes“ Altern nicht erfüllen zu können und fühlte sich entsprechend schlecht.

Schlussfolgerung

Mediale Altersdarstellungen zeigen komplexe und scheinbar paradoxe Wirkungen. So treten negative Effekte für das Selbst- und Alterserleben bei älteren Menschen auf, wenn eine Altersdarstellung einseitig positiv ausfällt. Es kann vermutet werden, dass hierbei soziale Vergleichsprozesse stattfinden. Insgesamt bestätigt die Studienreihe, dass Altersbilder in ihren Auswirkungen auf die Wahrnehmung von Alterungs- und Gesundheitsprozessen hoch relevant sind.
Governance by Uncertainty: Changing Patterns in China’s Environmental Enforcement
Authors: van der Kamp Denise Sienli
Published: June 2023

Governance in China is often characterized as dualistic. On the one hand, the state invests in stable, rule-based institutions to support effective policy implementation. Yet the state also engages in sudden regulatory campaigns, overstepping its own laws to implement rapid changes in key sectors. Businesses in China have developed coping mechanisms to weather these uncertainties; they cultivate political ties or learn to accommodate unexpected disruptions. Yet in the sphere of environmental policy implementation, businesses across the spectrum are starting to complain that local environmental enforcement feels unpredictable, even arbitrary. What constitutes unpredictable enforcement in an environment already characterized by high levels of regulatory uncertainty? What changes in environmental enforcement are driving these complaints? Using original data on nine years of city-level enforcement measures, I show that both campaign-style and rule-based enforcement have been increasing in intensity and frequency since the mid-2010s. Through qualitative evidence, I show how these two approaches work at cross purposes, generating mixed signals on which strategies businesses should use to reduce pollution or to mitigate regulatory uncertainty. Data shows that this is a nationwide pattern, which explains why business—even experienced, well-connected businesses—are complaining about arbitrary state action. This study draws attention to emerging stress tests of China’s dualistic governance, while delving into what these changes portend for state-business relations in China.
On curves on Hirzebruch surfaces
Authors: Martens Gerriet
Published: June 2023

We call a smooth irreducible projective curve a Castelnuovo curve if it admits a birational map into the projective r-space such that the image curve has degree at least 2r+1 and the maximum possible geometric genus (which one can calculate by a classical formula due to Castelnuovo). It is well known that a Castelnuovo curve must lie on a Hirzebruch surface (rational ruled surface). Conversely, making use of a result of W. Castryck and F. Cools concerning the scrollar invariants of curves on Hirzebruch surfaces we show that curves on Hirzebruch surfaces are Castelnuovo curves unless their genus becomes too small w.r.t. their gonality. We analyze the situation more closely, and we calculate the number of moduli of curves of fixed genus g and fixed gonality k lying on Hirzebruch surfaces, in terms of g and k.
A Bilayer High-Temperature Dielectric Film with Superior Breakdown Strength and Energy Storage Density
Authors: Ping Jiang-Bo , Feng Qi-Kun , Zhang Yong-Xin , Wang Xin-Jie , Huang Lei , Zhong Shao-Long , Dang Zhi-Min
Published: June 2023

The further electrification of various fields in production and daily life makes it a topic worthy of exploration to improve the performance of capacitors for a long time, including thin-film capacitors. The discharge energy density of thin-film capacitors that serves as one of the important types directly depends on electric field strength and the dielectric constant of the insulation material. However, it has long been a great challenge to improve the breakdown strength and dielectric constant simultaneously. Considering that boron nitride nanosheets (BNNS) possess superior insulation and thermal conductivity owing to wide band gap and 2-dimensional structure, a bilayer polymer film is prepared via coating BNNS by solution casting on surface of polyethylene terephthalate (PET) films. By revealing the bandgap and insulating behavior with UV absorption spectrum, leakage current, and finite element calculation, it is manifested that nanocoating contributes to enhance the bandgap of polymer films, thereby suppressing the charge injection by redirecting their transport from electrodes. Worthy to note that an ultrahigh breakdown field strength (~ 736 MV m−1), an excellent discharge energy density (~ 8.77 J cm−3) and a prominent charge–discharge efficiency (~ 96.51%) are achieved concurrently, which is ascribed to the contribution of BNNS ultrathin layer. In addition, the modified PET films also have superior comprehensive performance at high temperatures (~ 120 °C). The materials and methods here selected are easily accessible and facile, which are suitable for large-scale roll-to-roll process production, and are of certain significance to explore the methods about film modification suitable for commercial promotion.
Mixed-effects location-scale model based on generalized hyperbolic distribution
Authors: Fujinaga Yuki , Masuda Hiroki
Published: June 2023

Motivated by better modeling ofintra-individualvariability in longitudinal data, we propose a class of location-scale mixed-effects models, in which the data of each individual is modeled by a parameter-varying generalized hyperbolic distribution. We first study the local maximum-likelihood asymptotics and reveal the instability in the numerical optimization of the log-likelihood. Then, we construct an asymptotically efficient estimator based on the Newton–Raphson method based on the original log-likelihood function with the initial estimator being naive least-squares-type. Numerical experiments are conducted to show that the proposed one-step estimator is not only theoretically efficient but also numerically much more stable and much less time-consuming compared with the maximum-likelihood estimator.
Functional and Sport-Specific Outcome Following Traumatic First-Time Shoulder Dislocation and Arthroscopic Surgical Repair in Rock Climbers
Authors: Simon Michael , Geffel Leonid , Lutter Christoph , Schöffl Volker
Published: June 2023

Introduction

Traumatic shoulder dislocations rank among the most common shoulder injuries in climbers, with rising numbers over the last years. The objective of this study was to analyze the outcome following traumatic first-time shoulder dislocation and subsequent surgical treatment in this population.

Methods

In a retrospective study, climbers who experienced a traumatic shoulder dislocation were treated with an arthroscopic repair of the labrum-ligament complex (LLC). The functional outcome was assessed with a standardized questionnaire and clinical examination, including the Constant Murley and Single Assessment Numeric Evaluation scores. The sport-specific outcome was analyzed using the Union Internationale des Associations d’Alpinisme (UIAA) scale of difficulty and a sport-specific outcome score.

Results

The functional and sport-specific outcome for 27 climbers (20 men; 7 women; 3 with bilateral injuries; age, 34±11 [17–61] y; data presented as mean±SD [range]) was assessed 53±29 (12–103) mo after surgery. The postoperative Constant Murley score was 95±8 (67–100) points. At follow-up, 93% (n=25) of patients had started climbing again. Twenty-one climbers (78%) reached a climbing level within the range of ±0.33 UIAA grades of their initial capability or even exceeded their preinjury grade. Only 7% (n=2) of the patients had a recurrent shoulder dislocation, leading to a secondary surgery, and, therefore, required ongoing postoperative treatment at the time of follow-up.

Conclusions

Arthroscopic repair of the LLC following first-time traumatic shoulder dislocation in climbers shows a good outcome and a low recurrence rate. After surgery, most patients are able to regain a high level of rock-climbing ability.
Language, Discourse and Anxiety
Authors: Collins Luke , Baker Paul
Published: June 2023

Why is language so important to the ways that we make sense of anxiety? This book uses corpus assisted discourse analysis to examine twenty-three million words of text posted to a forum for people with anxiety. It shows how linguistic techniques like catastrophisation and anthropomorphisation can result in very different conceptualisations of anxiety, as well as how aspects of identity like age, sex and cultural background can impact on understandings of anxiety and how it ought to be managed. It tracks the changing identities of posters, from their first posts to their last, and incorporates a range of corpus-based techniques to examine the language data, enabling consideration of interaction between participants and features associated with online forms of communication like emoji. It ultimately provides a step towards a better understanding of different responses to anxiety and aims to promote further engagement with this topic in the field of applied linguistics.
Privatization and Its Discontents
Authors: Titolo Matthew
Published: June 2023

In Privatization and Its Discontents, Matthew Titolo situates the contemporary debate over infrastructure in the long history of public–private governance in the United States. Titolo begins with Adam Smith's arguments about public works and explores debates over internal improvements in the early republic, moving to the twentieth-century regulatory state and public-interest liberalism that created vast infrastructure programs. While Americans have always agreed that creation and oversight of 'infrastructure' is a proper public function, Titolo demonstrates that public–private governance has been a highly contested practice throughout American history. Public goods are typically provided with both government and private actors involved, resulting in an ideological battle over the proper scope of the government sphere and its relationship to private interests. The course of that debate reveals that 'public' and 'private' have no inherent or natural content. These concepts are instead necessarily political and must be set through socially negotiated compromise.
Nostromo
Authors: Conrad Joseph
Published: June 2023

Joseph Conrad's Nostromo (1904) is widely considered his modernist masterpiece. The first of his major political novels, it depicts the effects of repeated revolution in a fictional South American state under the growing influence of the United States of America. It is an enduring portrait of global economics and politics during the late nineteenth and early twentieth centuries. This first comprehensive and authoritative critical edition offers an introduction clarifying the novel's origins and sources, while explanatory notes detail literary and historical references. An accompanying essay lays out the history of composition and publication, detailing interventions made by Conrad's editors. Also included are appendices of Conrad's source material; glossaries of nautical and foreign terms; a map; and reproductions of early drafts. By returning to (and respecting) Conrad's own early manuscript and typescript forms, this edition presents the novel and its preface in a form more authoritative than any so far.
Expressions, Speech Acts and Discourse
Authors: Edmondson Willis J. , House Juliane , Kadar Daniel Z.
Published: June 2023

First published in 1981, Let's Talk and Talk About It is regarded as a cornerstone of research in pragmatics, which laid new and lasting foundations for the teaching of English. Forty years on, this extensively updated version is fully tailored for the 21st century. It provides a pedagogic interactional grammar of English, designed for learners and teachers of English and textbook writers, as well as experts of pragmatics and applied linguistics. The book includes a rigorous pragmatic system through which interaction in English and other languages can be captured in a replicable way, covering pragmatically important expressions, types of talk and other interactional phenomena, as well as a ground-breaking interactional typology of speech acts. The book is also illustrated with a legion of interactional and entertaining examples, showing how the framework can be put to use. It will remain a seminal work in the field for years to come.
Steep ice – progress and future challenges in research on ice cliffs
Authors: Steiner Jakob F. , Buri Pascal , Abermann Jakob , Prinz Rainer , Nicholson Lindsey
Published: June 2023

Ice cliffs are features along ice sheet margins, along tropical mountain glaciers, at termini of mountain glaciers and on debris-covered glacier tongues, that have received scattered attention in literature. They cover small relative areas of glacier or margin surface respectively, but have been involved in two apparent anomalies. On the one hand, they have been identified as potential hotspots of extreme melt rates on debris-covered tongues contributing to their relatively rapid ablation, compared to the surrounding glacier surface. On the other hand, they appear where the ice margin is stable (or temporarily advancing) even under conditions of negative mass balance. In this manuscript, we recapitulate why ice cliffs remain interesting features to investigate and what we know about them so far. We conclude by suggesting to further investigate their genesis and variable morphology and their potential as windows into past climates and processes.
An Assessment of the Climate Damage Costs of European Short-Lived Climate Forcers
Authors: Åström Stefan , Källmark Lovisa
Published: June 2023

In addition to effects from greenhouse gases, climate change is affected by short-lived climate forcers (SLCF). These are often co-emitted with carbon dioxide, and some are regulated air pollutants. In the governance of these pollutants, established estimates of damage costs of pollution inform benefit–cost analyses. However, climate change impact of SLCFs is omitted from these estimates. The purpose of this study is to calculate economic damage costs of air pollutants’ effect on climate change and compare these with established damage costs. Focus is on European emissions governed in the EU National Emission Reduction Commitments Directive during 2020–2050. We use well-known SLCF emission metrics and multiply with literature values on social costs of methane to calculate climate damage costs of SLCFs. The results indicate that average absolute climate damage costs are highest for black carbon ($59,500/ton in 2050) and lowest for nonmethane volatile organic compounds ($661/ton). Our indicative values are likely underestimations. Indicative climate damage costs are usually lower than established damage costs, with notable exceptions. We propose that more detailed studies are necessary, and that inclusion of climate damage costs into economic valuation of SLCFs is important for future air pollution and climate benefit–cost analyses.
Non-local approximation of free-discontinuity problems in linear elasticity and application to stochastic homogenisation
Authors: Marziani Roberta , Solombrino Francesco
Published: June 2023

We analyse the $\Gamma$-convergence of general non-local convolution type functionals with varying densities depending on the space variable and on the symmetrized gradient. The limit is a local free-discontinuity functional, where the bulk term can be completely characterized in terms of an asymptotic cell formula. From that, we can deduce an homogenisation result in the stochastic setting.
PREVENTING THE INFINITE REGRESS: DISCRETION, BARS TO RELIEF AND THE STRUCTURE OF EQUITY
Authors: Tiverios Nicholas A.
Published: June 2023

A growing body of literature has emphasised the role of equity as a body of second order principles. These scholars argue that what makes equity distinct is that it assumes a particular outcome at common law, but then controls or disables one party's insistence on her legal entitlements. Where do equitable bars to relief fit within such accounts? This article argues that equitable bars to relief fit comfortably with the view that equity is second order law. This is for a simple reason: equity prevents the unjust exercise of legal entitlements. However, equitable rules are also amenable to being exercised unjustly. To prevent equitable rules being abused, equitable doctrines require some limited discretion to be built in. If this were not the case, then the general law would require a third set of rules to control equity and then a fourth set of rules to control those rules (ad infinitum).
From State Warfare to State Welfare: Family Values in Leonard Freed'sPolice Work(1980)
Authors: SCHREIBER KIMBERLY
Published: June 2023

This article examines Leonard Freed's 1980Police Work, a photobook that documents the activities of the New York City Police Department from 1973 to 1979. It contextualizes the photobook within this liminal decade after the fullness of the civil rights movement and before the rise of austerity politics. The photobook, I argue, produces a visual repertoire of policing that resolves the crisis of legitimacy faced by the NYPD during this decade, remaking the meaning of the police in the public imaginary from an agent of state warfare into an institution of state welfare. Far from simply creating photographs of policing as community care,Police Workengages in a process by which police violence is visually recoded as police benevolence. The visual politics of the family are central to this process by which we are made not to see police brutality, even when it is placed vividly on display. Ultimately, I show how, even as the camera moves between public and private,Police Workproduces an ideology of separate spheres in which the expansion of policing can find its rationalization. Ultimately, this article revealsPolice Workas a site through which to examine the intimate, yet often disavowed, entanglements between the domestic and the carceral.
GOING TO SEE THE NYMPHS: LANDSCAPE AND RELIGIOUS EXPERIENCE AT THE ZAR TRYPA CAVE (MOUNT OSSA, THESSALY)
Authors: Blomley Anna Magdalena
Published: June 2023

This paper focuses on the little-known but important cave-sanctuary of Zar Trypa on Mount Ossa (modern Kissavos) in north-eastern Thessaly. In 1910, research conducted at the site uncovered remains of votives from the Classical, Hellenistic and Roman periods, including a group of eight inscriptions dedicated to the Nymphs. Despite this remarkable epigraphic assemblage, the site was not investigated beyond a single excavation season and today is largely unknown. Consequently, the Zar Trypa cave and its finds have never featured prominently in the discussion of Thessalian religion or of Greek ‘natural’ sanctuaries. Combining archival studies, on-site observations and GIS-based methods of landscape archaeology, this paper sets out to re-assess the surviving archaeological evidence from the Zar Trypa cave, to examine the spatial setting of ritual activity at the site, and to place the cave in the context of Mount Ossa's natural environment and ancient settlement pattern. Drawing on the methodological framework of ‘lived religion’, this assessment not only contributes towards our understanding of ancient religious experiences at the Zar Trypa cave, but also addresses broader questions such as the significance and meaning of ‘sacred travel’ in pre-Christian antiquity.
When low level of constraint and effectiveness go hand in hand: The example of the 2005 Convention
Authors: Guèvremont Véronique , Varin Clémence
Published: June 2023

The year 2022 marks 15 years since the entry into force of the United Nations Educational, Scientific and Cultural Organization’s 2005 Convention on the Protection and Promotion of the Diversity of Cultural Expressions. Among its objectives, this treaty aims at acknowledging the specific nature – economic and cultural – of cultural activities, goods, and services, reaffirming the sovereign right of states to adopt or implement measures they deem appropriate for the protection and the promotion of the diversity of cultural expressions as well as reinforcing international cooperation for more balanced cultural exchanges. Since its adoption, this treaty has been criticized for its low level of constraint. However, data collected over the years show that parties rely extensively on the Convention to undertake diverse initiatives to achieve the treaty’s objectives. Based on concrete examples, this article aims to show that the effectivity of a legal instrument does not only rely on its degree of constraint but also on other factors, including monitoring mechanisms put in place in the context of its implementation.
Reach and uptake of mass drug administration for worm infections through health facility-, school-, and community-based approaches in two districts of Zambia: a call for scale-up
Authors: Halwiindi Hikabasa , Chooka Lubombo , Phiri Masauso Moses , Tapisha Buumba , Masenga Sepiso K. , Mudenda Jolezya , Chimfwembe Kingford , Mugode Mwitwa , Hamooya Benson M.
Published: June 2023

Helminthiases cause significant health deficiencies among children. Mass administration of anthelminthic drugs has had significant results to counter these effects. We assessed the effects on and determinants of treatment coverage of community-directed treatment among children in Zambia, using cross-sectional survey data, and using chi-square test and multilevel mixed-effects model. Of 1,416 children, 51.5% were males and 48.5% were females, while 52.7%, were school-age, and 47.3% were preschool-age. Overall treatment coverage was 53.7% (95% confidence interval (CI) 51.1, 56.4). More preschool-age children were treated compared to school-age ones, 65.2% versus 43.4%, P < 0.001. Similarly, more children under community-directed intervention were treated compared to regular mass drug administration (65.2% versus 51.1 %, P < 0.001). Treatment among school-age participants was associated with being male (Adjusted Odds Ratio (AOR 1.83, 95%CI 1.23–2.72), receiving community-directed treatment (AOR 5.53; 95%CI 3.41–8.97), and shorter distance to health facility (AOR 2.20; 95%CI 1.36–3.56). Among preschool-aged participants, treatment was associated with being residents of Siavonga district (AOR 0.03; 95%CI 0.01–0.04) and shorter distance to health facility (AOR 0.35; 95%CI 0.21–0.59). Community-directed treatment can be used to increase treatment coverage, thereby contribute to 2030 vision of ending epidemics of neglected tropical diseases.
Hanging over the Void. Uses of Long Ropes and Climbing Rope Ladders in Prehistory as Illustrated in Levantine Rock Art
Authors: Bea Manuel , Roman Dídac , Domingo Inés
Published: June 2023

Direct or indirect evidence of ropemaking are scarce in European prehistory. Only a few references to Middle or Upper Palaeolithic remains are known to us, with more examples towards the Holocene. The archaeological contexts of ropes offer little information about possible uses, as the activities they are used for are often archaeologically invisible. However, some rock-art traditions shed some light on potential uses, worth exploring. In Spain, Levantine rock art offers the best graphic examples across Europe showing various uses of ropes, including climbing. Starting from the recently discovered climbing scene of Barranco Gómez site (Teruel, Spain), including the best preserved and more complex use of ropes seen so far in Levantine art, this paper analyses representations of ropes in this art, as well as their varieties and diverse uses. Our study suggests that different rope-making techniques were used by Levantine societies, which we believe are indicative of a complex rope-making technology, requiring a considerable investment of time and efforts. It also shows a certain variety of rope climbing techniques and rope climbing gear, illustrating that both were mastered by Levantine societies. Moreover, a preferential use of ropes in honey-hunting scenes is observed.
Comparison of foods and beverages served and consumed in Child and Adult Care Food Program-participating childcare centres to national guidelines
Authors: Mozaffarian Rebecca S , Carter Sonia , Bovenzi Mary C , Kenney Erica L
Published: June 2023

Objective:

The federal Child and Adult Care Food Program (CACFP) sets minimum nutrition and portion size standards for meals served in participating childcare programs. CACFP has been associated with more nutritious meals served. It is unclear, however, whether CACFP results in children’s dietary intake being aligned with national recommendations. We assess whether children’s dietary intake in CACFP-participating childcare centres meets benchmarks set by the Dietary Guidelines for Americans (DGA).

Design:

This is a cross-sectional study. We used direct observation to estimate quantities of foods/beverages served and consumed per child. Mean amounts served per child per day were compared with CACFP portion size requirements for each component (fruits, vegetables, milk and meat/meat alternate). Mean amounts of foods/beverages consumed were compared with DGA recommendations (energy content, fruits, vegetables, whole/refined grains, dairy, protein and added sugars). One sample t-tests evaluated if quantities served and consumed were different from CACFP and DGA standards, respectively.

Setting:

Six CACFP-participating childcare centres.

Participants:

2–5 year-old children attending childcare.

Results:

We observed forty-six children across 166 child meals. Most meals served met CACFP nutrition standards. Compared with CACFP portion size standards, children were served more grains at breakfast and lunch; more fruits/vegetables at lunch but less at breakfast and snack and less dairy at all eating occasions. Compared with DGA recommendations, children under-consumed every food/beverage category except grains during at least one eating occasion.

Conclusions:

Children were served quantities of foods/beverages mostly consistent with CACFP portion size requirements, but had sub-optimal intake relative to DGA. More research is needed to help children consume healthy diets in childcare.
Turbulent Energy Transfer at Dipolarization Fronts
Authors: Liu C. M. , Cao J. B. , Xing X. N. , Chen Z. Z.
Published: June 2023

Dipolarization fronts (DFs), ion‐scale magnetic transients characterized by dramatic enhancement of northward magnetic field, have been documented as crucial energy transfer regions in the magnetosphere. DF‐driven energy transfer has hitherto been studied mainly in the laminar regime. Energy transfer driven by turbulent processes, however, remains unclear. Here we perform a comprehensive investigation of turbulent energy transfer (TET) developed at DFs, via using high‐cadence data from Magnetospheric Multiscale mission. We find that: (a) TET is equally governed by energy loads and generators, different from laminar energy transfer which is typically dominated by energy loads; (b) ion and electron currents play comparable roles in driving TET; (c) TET is positively correlated with local magnetic field strength and ion speed; (d) TET shows asymmetric global distributions along the dawn‐dusk direction. These features implicate that TET is primarily related to electromagnetic turbulence at electron‐ion hybrid scales. These new results, uncovering unique characteristics of DF‐driven TET, can deeply advance our understanding of energy budgets in the magnetosphere.
Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia
Authors: Liu-Lupo Yunpeng , Ham James Dongjoo , Jeewajee Swarna K. A. , Nguyen Lan , Delorey Toni , Ramos Azucena , Weinstock David M. , Regev Aviv , Hemann Michael T.
Published: June 2023

Whole chromosome losses resulting in near-haploid karyotypes are found in a rare subgroup of treatment-refractory acute lymphoblastic leukemia. To systematically dissect the unique physiology and uncover susceptibilities that can be exploited in near-haploid leukemia, we leveraged single-cell RNA-Seq and computational inference of cell cycle stages to pinpoint key differences between near-haploid and diploid leukemia cells. Combining cell cycle stage-specific differential expression with gene essentiality scores from a genome-wide CRISPR-Cas9-mediated knockout screen, we identified the homologous recombination pathway component RAD51B as an essential gene in near-haploid leukemia. DNA damage analyses revealed significantly increased sensitivity of RAD51-mediated repair to RAD51B loss in the G2/M stage of near-haploid cells, suggesting a unique role of RAD51B in the homologous recombination pathway. Elevated G2/M and G1/S checkpoint signaling was part of a RAD51B signature expression program in response to chemotherapy in a xenograft model of human near-haploid B-ALL, and RAD51B and its associated programs were overexpressed in a large panel of near-haploid B-ALL patients. These data highlight a unique genetic dependency on DNA repair machinery in near-haploid leukemia and demarcate RAD51B as a promising candidate for targeted therapy in this treatment-resistant disease.
A historical review of 'phossy jaw'
Authors: Devlin Hugh
Published: June 2023

The aim of this article is to stimulate interest and discussion on the pathogenesis of 'phossy jaw'. Historical evidence from newspapers and articles of the time is presented, as other scientific evidence is largely absent. It has stimulated considerable interest in present-day media due to the struggles of nineteenth century reformers to improve working conditions against an apathetic government and weak enforcement of regulation. Those afflicted were often young women who suffered severe pain, loss of segments of jaw, and disfigurement.
Nuclear complement C3b promotes paclitaxel resistance by assembling the SIN3A/HDAC1/2 complex in non-small cell lung cancer
Authors: Wang Xiaochao , Hao Yan , Chen Jianfeng , Ding Peipei , Lv Xinyue , Zhou Danlei , Li Ling , Li Luying , Xu Yanqing , Zhu Yumeng , Zhang Wei , Chen Lu , Liao Tian , He Xianghuo , Ji Qing-Hai , Hu Weiguo
Published: June 2023

In addition to the classical role as a serum effector system of innate immunity, accumulating evidence suggests that intracellular complement components have indispensable functions in immune defense, T cell homeostasis, and tumor cell proliferation and metastasis. Here, we revealed that complement component 3 (C3) is remarkably upregulated in paclitaxel (PTX)-resistant non-small cell lung cancer (NSCLC) cells and that knockdown of C3 promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy. Ectopic C3 decreased PTX-induced apoptosis and induced resistance to PTX treatment in original NSCLC cells. Interestingly, C3b, the activated fragment of C3, was found to translocate into the nucleus and physically associate with the HDAC1/2-containing SIN3A complex to repress the expression of GADD45A, which plays an important role in cell growth inhibition and apoptosis induction. Importantly, C3 downregulated GADD45A by enhancing the binding of the SIN3A complex with the promoter of GADD45A, thus decreasing the H3Ac level to compress chromatin around the GADD45A locus. Subsequently, ectopic GADD45A promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy, and insufficiency of GADD45A in original cancer cells induced resistance to PTX treatment. These findings identify a previously unknown nucleus location and oncogenic property for C3 in chemotherapy and provide a potential therapeutic opportunity to overcome PTX resistance.
Drosophila motor neuron boutons remodel through membrane blebbing coupled with muscle contraction
Authors: Fernandes Andreia R. , Martins João P. , Gomes Edgar R. , Mendes César S. , Teodoro Rita O.
Published: June 2023

Wired neurons form new presynaptic boutons in response to increased synaptic activity, however the mechanism(s) by which this occurs remains uncertain. Drosophila motor neurons (MNs) have clearly discernible boutons that display robust structural plasticity, being therefore an ideal system in which to study activity-dependent bouton genesis. Here, we show that in response to depolarization and in resting conditions, MNs form new boutons by membrane blebbing, a pressure-driven mechanism that occurs in 3-D cell migration, but to our knowledge not previously described to occur in neurons. Accordingly, F-actin is decreased in boutons during outgrowth, and non-muscle myosin-II is dynamically recruited to newly formed boutons. Furthermore, muscle contraction plays a mechanical role, which we hypothesize promotes bouton addition by increasing MN confinement. Overall, we identified a mechanism by which established circuits form new boutons allowing their structural expansion and plasticity, using trans-synaptic physical forces as the main driving force.
A crucial role for dynamic expression of components encoding the negative arm of the circadian clock
Authors: Wang Bin , Zhou Xiaoying , Kettenbach Arminja N. , Mitchell Hugh D. , Markillie Lye Meng , Loros Jennifer J. , Dunlap Jay C.
Published: June 2023

In the Neurospora circadian system, the White Collar Complex (WCC) drives expression of the principal circadian negative arm component frequency (frq). FRQ interacts with FRH (FRQ-interacting RNA helicase) and CKI, forming a stable complex that represses its own expression by inhibiting WCC. In this study, a genetic screen identified a gene, designated as brd-8, that encodes a conserved auxiliary subunit of the NuA4 histone acetylation complex. Loss of brd-8 reduces H4 acetylation and RNA polymerase (Pol) II occupancy at frq and other known circadian genes, and leads to a long circadian period, delayed phase, and defective overt circadian output at some temperatures. In addition to strongly associating with the NuA4 histone acetyltransferase complex, BRD-8 is also found complexed with the transcription elongation regulator BYE-1. Expression of brd-8, bye-1, histone h2a.z, and several NuA4 subunits is controlled by the circadian clock, indicating that the molecular clock both regulates the basic chromatin status and is regulated by changes in chromatin. Taken together, our data identify auxiliary elements of the fungal NuA4 complex having homology to mammalian components, which along with conventional NuA4 subunits, are required for timely and dynamic frq expression and thereby a normal and persistent circadian rhythm.
Super-resolved trajectory-derived nanoclustering analysis using spatiotemporal indexing
Authors: Wallis Tristan P. , Jiang Anmin , Young Kyle , Hou Huiyi , Kudo Kye , McCann Alex J. , Durisic Nela , Joensuu Merja , Oelz Dietmar , Nguyen Hien , Gormal Rachel S. , Meunier Frédéric A.
Published: June 2023

Single-molecule localization microscopy techniques are emerging as vital tools to unravel the nanoscale world of living cells by understanding the spatiotemporal organization of protein clusters at the nanometer scale. Current analyses define spatial nanoclusters based on detections but neglect important temporal information such as cluster lifetime and recurrence in “hotspots” on the plasma membrane. Spatial indexing is widely used in video games to detect interactions between moving geometric objects. Here, we use the R-tree spatial indexing algorithm to determine the overlap of the bounding boxes of individual molecular trajectories to establish membership in nanoclusters. Extending the spatial indexing into the time dimension allows the resolution of spatial nanoclusters into multiple spatiotemporal clusters. Using spatiotemporal indexing, we found that syntaxin1a and Munc18-1 molecules transiently cluster in hotspots, offering insights into the dynamics of neuroexocytosis. Nanoscale spatiotemporal indexing clustering (NASTIC) has been implemented as a free and open-source Python graphic user interface.
Ligand effect on switching the rate-determining step of water oxidation in atomically precise metal nanoclusters
Authors: Liu Zhihe , Tan Hua , Li Bo , Hu Zehua , Jiang De-en , Yao Qiaofeng , Wang Lei , Xie Jianping
Published: June 2023

The ligand effects of atomically precise metal nanoclusters on electrocatalysis kinetics have been rarely revealed. Herein, we employ atomically precise Au25nanoclusters with different ligands (i.e., para-mercaptobenzoic acid, 6-mercaptohexanoic acid, and homocysteine) as paradigm electrocatalysts to demonstrate oxygen evolution reaction rate-determining step switching through ligand engineering. Au25nanoclusters capped by para-mercaptobenzoic acid exhibit a better performance with nearly 4 times higher than that of Au25NCs capped by other two ligands. We deduce that para-mercaptobenzoic acid with a stronger electron-withdrawing ability establishes more partial positive charges on Au(I) (i.e., active sites) for facilitating feasible adsorption of OH–in alkaline media. X-ray photo-electron spectroscopy and theoretical study indicate a profound electron transfer from Au(I) to para-mercaptobenzoic acid. The Tafel slope and in situ Raman spectroscopy suggest different ligands trigger different rate-determining step for these Au25nanoclusters. The mechanistic insights reported here can add to the acceptance of atomically precise metal nanoclusters as effective electrocatalysts.
Direct determination of high-order transverse ligand field parameters via µSQUID-EPR in a Et4N[160GdPc2] SMM
Authors: Taran Gheorghe , Moreno-Pineda Eufemio , Schulze Michael , Bonet Edgar , Ruben Mario , Wernsdorfer Wolfgang
Published: June 2023

The development of quantum technologies requires a thorough understanding of systems possessing quantum effects that can ultimately be manipulated. In the field of molecular magnetism, one of the main challenges is to measure high-order ligand field parameters, which play an essential role in the relaxation properties of SMMs. The development of highly advanced theoretical calculations has allowed the ab-initio determination of such parameters; however, currently, there is a lack of quantitative assessment of how good the ab-initio parameters are. In our quest for technologies that can allow the extraction of such elusive parameters, we develop an experimental technique that combines the EPR spectroscopy and µSQUID magnetometry. We demonstrate the power of the technique by performing EPR-µSQUID measurement of a magnetically diluted single crystal of Et4N[GdPc2], by sweeping the magnetic field and applying a range of multifrequency microwave pulses. As a result, we were able to directly determine the high-order ligand field parameters of the system, enabling us to test theoretical predictions made by state-of-the-art ab-initio methods.
Multi-chiral materials comprising metallosupramolecular and covalent helical polymers containing five axial motifs within a helix
Authors: Rey- Tarrío Francisco , Quiñoá Emilio , Fernández Gustavo , Freire Félix
Published: June 2023

Supramolecular and covalent polymers share multiple structural effects such as communication mechanisms among monomer repeating units, which are related to their axial helical structure. Herein, a unique multi-helical material combining information from both metallosupramolecular and covalent helical polymers is presented. In this system, the helical structure described by the poly(acetylene) (PA) backbone (cis-cisoidal,cis-transoidal) guides the pendant groups in a fashion where a tilting degree emerges between a pendant and the adjacent ones. As a result, a multi-chiral material is formed comprising four or five axial motifs when the polyene skeleton adopts either acis-transoidalorcis-cisoidalconfiguration: the two coaxial helices—internal and external—and the two or three chiral axial motifs described by the bispyridyldichlorido PtIIcomplex array. These results show that complex multi-chiral materials can be obtained by polymerizing appropriate monomers that combine both point chirality and the ability to generate chiral supramolecular assemblies.
B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma
Authors: Crescioli Silvia , Correa Isabel , Ng Joseph , Willsmore Zena N. , Laddach Roman , Chenoweth Alicia , Chauhan Jitesh , Di Meo Ashley , Stewart Alexander , Kalliolia Eleni , Alberts Elena , Adams Rebecca , Harris Robert J. , Mele Silvia , Pellizzari Giulia , Black Anna B. M. , Bax Heather J. , Cheung Anthony , Nakamura Mano , Hoffmann Ricarda M. , Terranova-Barberio Manuela , Ali Niwa , Batruch Ihor , Soosaipillai Antoninus , Prassas Ioannis , Ulndreaj Antigona , Chatanaka Miyo K. , Nuamah Rosamund , Kannambath Shichina , Dhami Pawan , Geh Jenny L. C. , MacKenzie Ross Alastair D. , Healy Ciaran , Grigoriadis Anita , Kipling David , Karagiannis Panagiotis , Dunn-Walters Deborah K. , Diamandis Eleftherios P. , Tsoka Sophia , Spicer James , Lacy Katie E. , Fraternali Franca , Karagiannis Sophia N.
Published: June 2023

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.
Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration
Authors: Molina-Gonzalez Irene , Holloway Rebecca K. , Jiwaji Zoeb , Dando Owen , Kent Sarah A. , Emelianova Katie , Lloyd Amy F. , Forbes Lindsey H. , Mahmood Ayisha , Skripuletz Thomas , Gudi Viktoria , Febery James A. , Johnson Jeffrey A. , Fowler Jill H. , Kuhlmann Tanja , Williams Anna , Chandran Siddharthan , Stangel Martin , Howden Andrew J. M. , Hardingham Giles E. , Miron Veronique E.
Published: June 2023

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned male mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.
TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR
Authors: Ran Xiang-Hong , Zhu Jia-Wu , Ni Run-Ze , Zheng Yong-Tang , Chen Ya-Yun , Zheng Wei-Hua , Mu Dan
Published: June 2023

Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment.