bluuebunny/crossref_metadata_2025 huggingface dataset:
Music Archaeology: Some Methodological and Theoretical Considerations
Authors: Both Arnd Adje
Published: August 2022

In its broadest sense, music archaeology is the study of the phenomenon of past musical behaviours and sound. This cross-disciplinary discipline comprises a series of approaches, including archaeological and musicological perspectives. The basis of research is music-related material finds, such as excavated and otherwise conservedsound artefacts(or ancient tools for sound and music production), as well as depictions of instrumentalists, singers, and dancers showing musical instruments and performance postures, sometimes including views of the original settings. As various archaeological cultures left such finds, many of the sociocultural contexts and meanings of past music can be studied. Today it is widely accepted that finds and depictions of ancient musical instruments are not only markers of musical traditions in space and time—especially when the archaeological contexts are well documented—but also a valuable means for experimentally testing ancient playing techniques. In the case of original sound artefacts (or their replicas), their acoustic function and the basic acoustic characteristics of a once performed music can also be reproduced and analysed. Additionally, acoustic spaces, such as architectural structures, caves, and other natural places, are the subject of music archaeological studies. The information obtained from the archaeological record can be deepened considerably when ancient scripts, historical treaties, and other written sources concerning music are related. Such documents offer notes on performance practices and their sociocultural contexts. For some cultures, hints concerning ancient music theory and musical aesthetics may also be found and, if ancient notations are related, even clues to aspects of musical structures are provided. Finally, the study of contemporary music cultures in which past musical traditions are preserved is valuable for comparative studies. In this paper the virtues of studying these sources are defined, but the limits of music archaeological research are also considered.
New Developments in the Social History of Music and Musicians in Ancient IRAQ, SYRIA, and Turkey
Authors: Mirelman Sam
Published: August 2022

The ancient cultures of Iraq, Syria, and Turkey are distinguished by the existence of extensive documentation in cuneiform script, amongst which are texts concerning music and musicians. Along with a common script, a common corpus of terms (with local variants) for instruments, musicians, theory, and performance, were transmitted in various languages and dialects in the third and second millennia BCE. Apart from later sources from ancient Greece, only ancient Egypt can compare in terms of the extent of textual information in the region. In contrast, the musical cultures of ancient Iran are known mostly through iconography and remains of musical instruments (Lawergren 2009). The same is true for Israel/Palestine, where the sources are essentially material, apart from the Old Testament and a handful of other texts (Braun 2002).
Musical Faces of Croatian Multiculturality
Authors: Ceribasic Naila
Published: August 2022

When I started the journey of writing this essay, I wondered at length what topic to propose and what tone it should take. Since theYearbook for Traditional Musicis a highly respected, international ethnomusicological journal, should I speak as an exponent of a small national ethnomusicology or am I allowed to take a more personal stance? Should I use this space for more canonized thoughts or could I allow myself to propose untested ones, to speak from this specific moment, inspired by recent musical events and readings? Although ethnomusicologists at home tend to be resentful when treated as only the providers of ethnographic material, should I present information in its historical, political, and social context or could I try to put forward some broader ethnomusicological thoughts?
The “Invisible” Dimension of Zorba's Dance
Authors: Zografou Magda , Pateraki Mimina
Published: August 2022

The methodological shift in cultural studies from observation to meaning (Geertz 1973) resulted in “invisible” dance action coming to the forefront of contemporary speculation in the humanistic and social sciences (Farnell 2001b:2). As Adrienne Kaeppler observes, it cannot be considered adequate to pinpoint whatever message we receive from the visually perceived manifestation of any choreography, because this visible dimension constitutes only one component of a larger social action. In order to develop an opinion of what and how a dance communicates in a specific circumstance, we must comprehend it as a holistic entity. According to Kaeppler, the creative process of understanding dance can be interpreted in a more obvious way: from within the dancer's ability and the spectator's knowledge of the metaphor applied in the dance motion, in light of the more general social and cultural environment. Following this argument, that the “visible” and “invisible” may emerge in all their dimensions (Kaeppler 2001:31–39), dance cannot be perceived solely as form; it has a usage and an orbit that emphasize the “human” and the “social,” while most of the time concealing its invisible and loaded symbolic aspects.
Turning Points: Has Ethnomusicology Lost Its Way?
Authors: McLean Mervyn
Published: August 2022

As some readers may know, I have recently published a book entitled Pioneers of Ethnomusicology. In it I try to answer the questions

What were the events that led to the emergence of ethnomusicology? Who were the prime movers? What motivated them? What influences were brought to bear on them, and what were the consequences? (McLean 2006: 11)
Tropes of Longing and Belonging: Nostalgia and Musical Instruments in Northeast Arnhem Land
Authors: Toner P.G.
Published: August 2022

In the musical traditions of the Yolngu of northeast Arnhem Land, in northern Australia, the evocation of ancestrally-significant places is of primary ideological and aesthetic importance. This is primarily done through song texts, when a singer “paints a picture” of a place in the mind's eye of the audience; when done with great skill, such evocation can produce strong feelings of nostalgia as listeners recall those places and the personal and ancestral events which took place there. Musical instruments can also be used in this way, either through tropes in the song texts, which make reference to the instrument and its ancestral significance, or through the actual sound of the instrument as an enacted trope during the musical performance itself. In either case, the mention or use of musical instruments can resonate powerfully with ideas about ancestors, people and places, making musical instruments important symbols in Yolngu culture.
On Metaphor and Analogy in the Concepts and Classification of Musical Instruments in Aceh
Authors: Kartomi Margaret
Published: August 2022

Artists, scholars and audiences in Aceh, the northernmost province of Sumatra, conceive of their percussive, wind and string instruments as symbolising Aceh's “glorious past” and attach a variety of metaphorical and analogous meanings to them. Implicit in the culture, and formulated explicitly by Acehnese scholars, is a classification that divides the instruments at the most general level into three main categories, or metaphorical socio-historical streams: those associated primarily with (i) the pre-Islamic ancestral and nature venerating (animist-Hindu) stream, practices, or presumed origins (ii) the Sunni and/or Syiah Islamic stream (including borderline cases of instruments that straddle both Islamic and animist practices), and (iii) the European or Western socio-historical stream. Organological sub-categories at the second level of categorical thinking are based on an instrument's manner of exciting sound, while the third level comprises the instrumental types with their local names. The instruments are also attributed with broader, changing sociocultural meanings, including gender and class divisions.
Symbolic and Social Transformation in the Lute Cultures of Crete: Music, Technology and the Body in a Mediterranean Society
Authors: Dawe Kevin
Published: August 2022

This article considers the role of lute culture (specifically, the lyra) in a Mediterranean society. Cretan lute cultures have historical roots imagined and otherwise which entangle them completely in a local musical and social world. My research into Cretan musical instrument cultures among others have demanded not only a scholarly response to new questions but also the construction and application of a broad theoretical and analytical framework with which to try and understand lute worlds. It is within this cultural and academic context, therefore, that I probe the relationship of music, technology, and the body and how these connections are configured in a Cretan-Mediterranean context, in symbol and metaphor, and as engendered and socially active, existing where musical and social practices coalesce. Therefore broader and theoretically demanding questions must form the basis of an opening discussion as defining of an approach and preparing the ground for a focussed study of the Cretan context.
Hardcore Muslims: Islamic Themes in Turkish Rap in Diaspora and in the Homeland
Authors: Solomon Thomas
Published: August 2022

At the beginning of the twenty-first century, Islam has, according to various estimates, between 900 million and 1.4 billion adherents in more than fifty countries, making it the second-largest religion in the world. Rap music and hip-hop youth culture have also, in their brief history, achieved global status, as the essays in Tony Mitchell's edited volume Global Noise (2001b) illustrate. It is perhaps not surprising that the long-standing world religion Islam and the more recently global musical genre of rap have intersected in various ways. Both the religion and the musical genre have spread over the globe as people and ideas move around, and people use the material and expressive resources at their disposal in practices of identity construction. It is not necessarily contradictory or paradoxical that some people may find it useful and compelling to imagine their identities using both Islam and rap music.
Research on Early Notations for the History of Tωgaku and Points of Scholarly Contention in their Interpretation
Authors: Marett Allan
Published: August 2022

It is now almost forty years since Laurence Picken first suggested that present-day performances of tωgaku—the repertory of Japanese court music (gagaku) that was originally imported from Tang China to Japan during the seventh to the ninth centuries—bear little or no resemblance to Chinese music of the Tang period (618-907 CE), or indeed any subsequent period. This was the first time that any scholar had challenged the ideology that modern tωgaku perfectly preserves the inheritance from Tang China, an ideology that had been developed in the nineteenth century during the official standardization of gagaku. Picken based his views on preliminary study of tωgaku tablature notations—which he saw as containing important clues about the relationship of the modern inheritance to the original Chinese forms of the repertory—and on study of surviving Chinese notations (Picken 1967, 1969; see also Marett 1986 for a more detailed summary of this research).
“He's not a White Man, He's A Small Bird Like You and Me”: Learning to Dance and Becoming Human in Southern New Ireland
Authors: Wolffram Paul
Published: August 2022

In the Lak region of southern New Ireland, Papua New Guinea, music and dance performance is not a discreet element of society; it is in performances that communities show others who they are, what they consist of and how powerful they can be. It is also in a performance that “individuals” (in the Lak sense of the term) display their identity and reveal their spiritual capacity. In addition it is in performance that the visible reality of humans meets the invisible realm of the spirits. The movement and costume elements of performance are the visual poetic representation of the spirit and human worlds as cast by the local imagination. Unlike many Highlands Papua New Guinea societies, where dance movements are kept to a minimum in order to accommodate elaborate costumes (Strathern 1979:244), among the Lak, dance movement is vigorous, powerful, and essential to a community's successful existence. Dance movements, which predominantly occur on the vertical plane (see Kaeppler and Niles 1998:482), differ significantly in style between the sexes; as Eves has recognized (1998:54), these movements are a definitive aspect of “gender conceptualisations” in the region. For male performers (and this article mainly focuses on men's dances), performance is a physical and spiritual display that transforms participants into something more than human. This article begins by introducing several key Lak notions. Local concepts concerning the individual, relationships, community, and male and female are explored. The mythical foundation of society is introduced as a basis for comprehending some of the aesthetics and emotions that underpin performance. And Lak notions surrounding the relationships between space, gender, and power are examined to reveal the invisible boundaries that divide the physical landscape.
Functions of Ceremonial Wedding Tunes, Svadobné Nôty, in the Context of Traditional Culture in Slovakia and in a Cross-Cultural Perspective
Authors: Važanová Jadranka
Published: August 2022

Within the varied repertoire of songs sung in the course of the traditional village wedding ceremony in Slovakia, specific songs were performed—usually by women without instrumental accompaniment—at particular, mostly ritual moments with context-appropriate texts to one or two recurring, locally identified wedding tunes called svadobné nôty. Today, these songs are still known by village people and are occasionally also performed within or outside the wedding context. Moreover, this phenomenon of a common local wedding melody seems to be spread among the wedding traditions of central, southern, and eastern Europe, sharing the name (svadobný hlas, svadbarski glas, svatovski glas) and similar features (Važanová 1999).
Surrogate Speech of the Asante Ivory Trumpeters of Ghana
Authors: Kaminski Joseph S.
Published: August 2022

Surrogate speech is a phonological system by which word tones of a spoken language are represented in tones produced on a musical instrument. Ethnomusicologists regard this as a musical process. This article analyses the surrogate speech system of the Asante ivory trumpeters who perform at the royal courts of Ghana. The language of the Asante is Twi, which is tonal, based on two tones, high and low. The tones produced on the Asante's ivory trumpets outline the speech contours of the high and low spoken tones of Twi. The trumpet surrogate speech thus substitutes for spoken verse during rites wherein ordinary speech is not reverent enough, or previously, in combat and politics, wherein the surrogate speech functioned clandestinely to keep orders secret from enemies.
CORRECTING PTOLEMY AND ARISTOTLE: IBN AL-ṢALĀḤ ON MISTAKES IN THE ALMAGEST, ON THE HEAVENS, AND POSTERIOR ANALYTICS
Authors: Hullmeine Paul
Published: August 2022

The polymath Ibn al-Ṣalāḥ (d. 1154 CE) is known for a number of comparatively small treatises on specific aspects of ancient Greek mathematical and philosophical works. He devotes many of his works to greater or smaller errors that he found in the works by Euclid, Ptolemy, and Aristotle. The aim of the present paper, which focuses on three treatises on Ptolemy and Aristotle, is to describe Ibn al-Ṣalāḥ’s method and aim in these works. I argue that his treatises on the Almagest, On the Heavens, and Posterior Analytics follow a similar structure and that there is much value for modern research resulting from the bibliographical details provided by Ibn al-Ṣalāḥ. To give but just one example, Ibn al-Ṣalāḥ attests to the existence of a so far unknown Arabic translation of Aristotle's Posterior Analytics. In this way, this paper is the first to establish Ibn al-Ṣalāḥ’s research profile: his works tell us which sources were available to scholars active in Baghdad and Damascus in the 12th century CE and how he tried to resolve contradictions from the different versions of authoritative texts. Thus, this paper enhances our knowledge of the Graeco-Arabic transmission of scientific and philosophical texts.
How taxes impact the choice between an annuity and the lump sum at retirement
Authors: Bütler Monika , Ramsden Alma
Published: August 2022

We analyze how taxes affect the choice between a life-long annuity and a one-off lump sum payment, the so-called annuitization decision. Using administrative data from a large Swiss pension fund, we impute taxes for the lump sum and the life-long annuity option. We show that taxes can explain a significant part of the variation in annuity rates. Exploiting kinks in the tax schedule of the one-off lump sum, we further find evidence for tax optimization strategies. Our findings suggest that individuals react strongly to tax incentives when making retirement choices.
Why do legislators rebel on trade agreements? The effect of constituencies’ economic interests
Authors: Stiller Yannick
Published: August 2022

Most trade agreements are ratified with overwhelming support by legislators throughout the world. This lack of opposition is surprising given the strong distributional consequences of trade and the expectation of conventional political economy theory that parliamentary votes on trade policy should be closely contested between winners and losers of globalization. To analyze the driving forces behind legislators’ voting behavior while avoiding the obscuring effect of party discipline, I analyze under which circumstances legislators decide to rebel against their party’s position when voting on the ratification of trade agreements. I put forward two hypotheses: First, rebellions are more likely when the trade agreement is with a larger trading partner and when the liberalization through the agreement is more comprehensive. Second, legislators will rebel when their party’s position does not align with their constituency’s economic interests. These hypotheses are supported by a series of multinomial regression analyses based on an original dataset comprising votes of several thousand legislators from multiple countries on the ratification of trade agreements.
Financial Uncertainty and Anxiety During the COVID-19 Pandemic
Authors: Yagil Dana , Cohen Miri
Published: August 2022

Abstract: Background: The COVID-19 pandemic involved many uncertainties, including financial uncertainty due to the global financial crisis. Previous research indicates that financial uncertainty is negatively related to mental health and wellbeing. Aims: We tested a model suggesting that the negative impact of financial uncertainty is explained by a restriction of individuals’ view of their future possibilities. Specifically, this longitudinal study explored the relationship of financial uncertainty and anxiety, considering the mediating role of future orientation. Method: Data were collected with questionnaires administered to Israeli citizens in April, June and August 2020. Data analysis comprised 379 respondents who participated in all three times. Results: Future orientation mediated the relationship of financial uncertainty and anxiety over time. Tests of changes across time show that changes in financial uncertainty were related to changes in anxiety levels over time. Limitations: Our sample was biased toward younger ages and the measurement of future orientation referred to a general view of the future rather than specific areas. Conclusion: The results suggest that the stressor of financial uncertainty is generalized to a negative view of future possibilities, thereby increasing anxiety.
Earth's Isostatic and Dynamic Topography—A Critical Perspective
Authors: Forte Alessandro M. , Rowley David B.
Published: August 2022

Earth's topography arises from the linear superposition of isostatic and dynamic contributions. The isostatic contribution reflects the distribution of thickness and density of the crust overlying a static, non‐convecting mantle. We argue that isostatic topography should be limited to the crust, thereby delimiting all sources for dynamic topography below the Moho. Dynamic topography is the component of the topography produced by normal stresses acting on the Moho that deflect the isostatic topography away from crustal isostatic equilibrium largely as a consequence of mantle flow dynamics. These normal stresses arise from pressure variations and vertical gradients of the radial flow in the convecting mantle. The best estimate of dynamic topography is from the residual topography, which is the difference between observed topography and crustal isostatic topography. Dynamic and residual topography are the same. It is clear that thermal anomalies horizontally advected by plate motions would not exist if the mantle were not convecting, therefore their contribution to topography is inherently dynamic in origin. The global integral of dynamic topography that encompasses all non‐crustal buoyancy sources is demonstrated to be equal to zero. It follows that mantle convection cannot change the mean radius or mean elevation of the Earth. Since changes in ocean basin volume driven by changes in mean depth of the oceans are inherently part of dynamic topography, thereby requiring that continental elevations must also change, such that the global integral of these perturbations must also be equal to zero. This constraint has important implications for global long‐term sea level and the stratigraphic record, among other features of the Earth system impacted by changes in Earth's dynamic topography.
Identifying Causal Interactions Between Groundwater and Streamflow Using Convergent Cross‐Mapping
Authors: Bonotto Giancarlo , Peterson Tim J. , Fowler Keirnan , Western Andrew W.
Published: August 2022

Groundwater (GW) is commonly conceptualized as causally linked to streamflow (SF). However, confirming where and how it occurs is challenging given the expense of experimental field monitoring. Therefore, hydrological modeling and water management often rely on expert knowledge to draw causality between SF and GW. This paper investigates the potential of convergent cross‐mapping (CCM) to identify causal interactions between SF and GW head. Widely used in ecology, CCM is a nonparametric method to identify causality in nonlinear dynamic systems. To apply CCM between variables the only required inputs are time‐series data (stream gauge and bore), so it may be an attractive alternative or complement to expensive field‐based studies of causality. Three upland catchments across different hydrogeologic settings and climatic conditions in Victoria, Australia, are adopted as case studies. The outputs of the method seem to largely agree with a priori perceptual understanding of the study areas and offered additional insights about hydrological processes. For instance, it suggested weaker SF‐GW interactions during and after the Millennium Drought than in the previous wet periods. However, we show that CCM limitations around seasonality, data sampling frequency, and long‐term trends could impact the variability and significance of causal links. Hence, care must be taken while physically interpreting the causal links suggested by CCM. Overall, this study shows that CCM can provide valuable causal information from common hydrological time‐series, which is relevant to a wide range of applications, but it should be used and interpreted with care and future research is needed.
Clumped‐Isotope Constraint on Upper‐Tropospheric Cooling During the Last Glacial Maximum
Authors: Banerjee Asmita , Yeung Laurence Y. , Murray Lee T. , Tie Xin , Tierney Jessica E. , Legrande Allegra N.
Published: August 2022

Ice cores and other paleotemperature proxies, together with general circulation models, have provided information on past surface temperatures and the atmosphere's composition in different climates. Little is known, however, about past temperatures at high altitudes, which play a crucial role in Earth's radiative energy budget. Paleoclimate records at high‐altitude sites are sparse, and the few that are available show poor agreement with climate model predictions. These disagreements could be due to insufficient spatial coverage, spatiotemporal biases, or model physics; new records that can mitigate or avoid these uncertainties are needed. Here, we constrain the change in upper‐tropospheric temperature at the global scale during the Last Glacial Maximum (LGM) using the clumped‐isotope composition of molecular oxygen trapped in polar ice cores. Aided by global three‐dimensional chemical transport modeling, we exploit the intrinsic temperature sensitivity of the clumped‐isotope composition of atmospheric oxygen to infer that the upper troposphere (effective mean altitude 10–11 km) was 6–9°C cooler during the LGM than during the late preindustrial Holocene. A complementary energy balance approach supports a minor or negligible steepening of atmospheric lapse rates during the LGM, which is consistent with a range of climate model simulations. Proxy‐model disagreements with other high‐altitude records may stem from inaccuracies in regional hydroclimate simulation, possibly related to land‐atmosphere feedbacks.
Locally Resolved Stress‐State in Samples During Experimental Deformation: Insights Into the Effect of Stress on Mineral Reactions
Authors: Cionoiu S. , Moulas E. , Stünitz H. , Tajčmanová L.
Published: August 2022

Understanding conditions in the Earth's interior requires data derived from laboratory experiments. Such experiments provide important insights into the conditions under which mineral reactions take place as well as processes that control the localization of deformation in the deep Earth. We performed Griggs‐type general shear experiments in combination with numerical models, based on continuum mechanics, to quantify the effect of evolving sample geometry of the experimental assembly. The investigated system is constituted by CaCO3 and the experimental conditions are near the calcite‐aragonite phase transition. All experimental samples show a heterogeneous distribution of the two CaCO3 polymorphs after deformation. This distribution is interpreted to result from local stress variations. These variations are in agreement with the observed phase‐transition patterns and grain‐size gradients across the experimental sample. The comparison of the mechanical models with the sample provides insights into the distribution of local mechanical parameters during deformation. Our results show that, despite the use of homogeneous sample material (here calcite), stress variations develop due to the experimental geometry. The comparison of experiments and numerical models indicates that aragonite formation is primarily controlled by the spatial distribution of mechanical parameters. Furthermore, we monitor the maximum pressure and σ1 that is experienced in every part of our model domain for a given amount of time. We document that local pressure (mean stress) values are responsible for the transformation. Therefore, if the role of stress as a thermodynamic potential is investigated in similar experiments, an accurate description of the state of stress is required.
The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights
Authors: Xiang Qian , Zhao Yongzhao , Lin Jialiang , Jiang Shuai , Li Weishi
Published: August 2022

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically.
m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer
Authors: Xu Weihong , Lai Yanan , Pan Yunqi , Tan Meiyu , Ma Yanyun , Sheng Huiming , Wang Jiucun
Published: August 2022

Gastric cancer (GC) is a malignancy with poor prognosis. NDUFA4 is reported to correlate with the progression of GC. However, its underlying mechanism in GC is unknown. Our study was to reveal the pathogenic mechanism of NDUFA4 in GC. NDUFA4 expression was explored in single-cell and bulk RNA-seq data as well as GC tissue microarray. Mitochondrial respiration and glycolysis were estimated by oxygen consumption rate and extracellular acidification rate, respectively. The interaction between NDUFA4 and METTL3 was validated by RNA immunoprecipitation. Flow cytometry was used to estimate cell cycle, apoptosis and mitochondrial activities. NDUFA4 was highly expressed in GC and its high expression indicated a poor prognosis. The knockdown of NDUFA4 could reduce cell proliferation and inhibit tumor growth. Meanwhile, NDUFA4 could promote glycolytic and oxidative metabolism in GC cells, whereas the inhibition of glycolysis suppressed the proliferation and tumor growth of GC. Besides, NDUFA4 inhibited ROS level and promoted MMP level in GC cells, whereas the inhibition of mitochondrial fission could reverse NDUFA4-induced glycolytic and oxidative metabolism and tumor growth of GC. Additionally, METTL3 could increase the m6A level of NDUFA4 mRNA via the m6A reader IGF2BP1 to promote NDUFA4 expression in GC cells. Our study revealed that NDUFA4 was increased by m6A methylation and could promote GC development via enhancing cell glycolysis and mitochondrial fission. NDUFA4 was a potential target for GC treatment.
Dominant-negative p53-overexpression in skeletal muscle induces cell death and fiber atrophy in rats
Authors: Langer Henning T. , Mossakowski Agata A. , Sule Rasheed , Gomes Aldrin , Baar Keith
Published: August 2022

The tumor suppressor p53 is thought to play a key role in the maintenance of cell size and homeostasis, but relatively little is known about its role in skeletal muscle. Based on its ability to suppress cell growth, we hypothesized that inhibiting the function of wild-type p53 through the overexpression of a dominant-negative p53 mutant (DDp53) could result in muscle fiber hypertrophy. To test this hypothesis, we electroporated adult rat tibialis anterior muscles with DDp53 and collected the tissue three weeks later. We confirmed successful overexpression of DDp53 on a histological and biochemical level and found pronounced changes to muscle architecture, metabolism, and molecular signaling. Muscle mass, fiber cross-sectional area, and fiber diameter significantly decreased with DDp53 overexpression. We found histopathological changes in DDp53 transfected muscle which were accompanied by increased levels of proteins that are associated with membrane damage and repair. In addition, DDp53 decreased oxidative phosphorylation complex I and V protein levels, and despite its negative effects on muscle mass and fiber size, caused an increase in muscle protein synthesis as assessed via the SUnSET technique. Interestingly, the increase in muscle protein synthesis was concomitant with a decrease in phospho-S6K1 (Thr389). Furthermore, the muscle wasting in the DDp53 electroporated leg was accompanied by a decrease in global protein ubiquitination and an increase in proteasome activity. In conclusion, overexpression of a dominant-negative p53 mutant in skeletal muscle results in decreased muscle mass, myofiber size, histological muscle damage, a metabolic phenotype, and perturbed homeostasis between muscle protein synthesis and degradation.
Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer
Authors: Zhang Dan , Tang Jing , Xu Yunhong , Huang Xiaoju , Wang Yilin , Jin Xin , Wu Gang , Liu Pian
Published: August 2022

Lysine crotonylation is a recently discovered post-translation modification involved in transcription regulation, cell signal transduction, and other processes. Scientists have identified several crotonylases and decrotonylases of histones, including P300/CBP, HDACs, and SIRTs. However, the regulation of non-histone protein crotonylation remains unclear. In the current study, we verified that crotonylation was upregulated in hypoxia and promoted liver cancer cell growth. We performed TMT-labeled quantitative lysine crotonylome analysis in 12 pairs of hepatocellular carcinoma and adjacent liver tissue and identified 3,793 lysine crotonylation sites in 1,428 proteins. We showed that crotonylation of lamin A at the site of K265/270 maintains its subcellular position, promotes liver cancer cell proliferation, and prevents cellular senescence. Our data indicate that HDAC6 is the decrotonylase of lamin A and downregulated in response to hypoxia, resulting in lamin A K265/270cr. Taken together, our study reveals the lamin A crotonylation in liver cancer progression and fills the research gap in non-histone protein crotonylation function.
Trends in COVID-19 hospital outcomes in England before and after vaccine introduction, a cohort study
Authors: Kirwan Peter D. , Charlett Andre , Birrell Paul , Elgohari Suzanne , Hope Russell , Mandal Sema , De Angelis Daniela , Presanis Anne M.
Published: August 2022

Widespread vaccination campaigns have changed the landscape for COVID-19, vastly altering symptoms and reducing morbidity and mortality. We estimate trends in mortality by month of admission and vaccination status among those hospitalised with COVID-19 in England between March 2020 to September 2021, controlling for demographic factors and hospital load. Among 259,727 hospitalised COVID-19 cases, 51,948 (20.0%) experienced mortality in hospital. Hospitalised fatality risk ranged from 40.3% (95% confidence interval 39.4–41.3%) in March 2020 to 8.1% (7.2–9.0%) in June 2021. Older individuals and those with multiple co-morbidities were more likely to die or else experienced longer stays prior to discharge. Compared to unvaccinated people, the hazard of hospitalised mortality was 0.71 (0.67–0.77) with a first vaccine dose, and 0.56 (0.52–0.61) with a second vaccine dose. Compared to hospital load at 0–20% of the busiest week, the hazard of hospitalised mortality during periods of peak load (90–100%), was 1.23 (1.12–1.34). The prognosis for people hospitalised with COVID-19 in England has varied substantially throughout the pandemic and according to case-mix, vaccination, and hospital load. Our estimates provide an indication for demands on hospital resources, and the relationship between hospital burden and outcomes.
Planktonic foraminifera organic carbon isotopes as archives of upper ocean carbon cycling
Authors: Hoogakker Babette A. A. , Anderson Caroline , Paoloni Tommaso , Stott Andrew , Grant Helen , Keenan Patrick , Mahaffey Claire , Blackbird Sabena , McClymont Erin L. , Rickaby Ros , Poulton Alex , Peck Victoria L.
Published: August 2022

The carbon cycle is a key regulator of Earth’s climate. On geological time-scales, our understanding of particulate organic matter (POM), an important upper ocean carbon pool that fuels ecosystems and an integrated part of the carbon cycle, is limited. Here we investigate the relationship of planktonic foraminifera-bound organic carbon isotopes (δ13Corg-pforam) with δ13Corg of POM (δ13Corg-POM). We compare δ13Corg-pforam of several planktonic foraminifera species from plankton nets and recent sediment cores with δ13Corg-POM on a N-S Atlantic Ocean transect. Our results indicate that δ13Corg-pforam of planktonic foraminifera are remarkably similar to δ13Corg-POM. Application of our method on a glacial sample furthermore provided a δ13Corg-pforam value similar to glacial δ13Corg-POM predictions. We thus show that δ13Corg-pforam is a promising proxy to reconstruct environmental conditions in the upper ocean, providing a route to isolate past variations in δ13Corg-POM and better understanding of the evolution of the carbon cycle over geological time-scales.
Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
Authors: Castro Julia T. , Azevedo Patrick , Fumagalli Marcílio J. , Hojo-Souza Natalia S. , Salazar Natalia , Almeida Gregório G. , Oliveira Livia I. , Faustino Lídia , Antonelli Lis R. , Marçal Tomas G. , Augusto Marconi , Valiate Bruno , Fiorini Alex , Rattis Bruna , Ramos Simone G. , Piccin Mariela , Nonato Osvaldo Campos , Benevides Luciana , Magalhães Rubens , Cassaro Bruno , Burle Gabriela , Doro Daniel , Kalil Jorge , Durigon Edson , Salazar Andrés , Caballero Otávia , Santiago Helton , Machado Alexandre , Silva João S. , da Fonseca Flávio , Fernandes Ana Paula , Teixeira Santuza R. , Gazzinelli Ricardo T.
Published: August 2022

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.
Mechanistic classification and benchmarking of polyolefin depolymerization over silica-alumina-based catalysts
Authors: Lee Wei-Tse , van Muyden Antoine , Bobbink Felix D. , Mensi Mounir D. , Carullo Jed R. , Dyson Paul J.
Published: August 2022

Carbon-carbon bond cleavage mechanisms play a key role in the selective deconstruction of alkanes and polyolefins. Here, we show that the product distribution, which encompasses carbon range and formation of unsaturated and isomerization products, serves as a distinctive feature that allows the reaction pathways of different catalysts to be classified. Co, Ni, or Ru nanoparticles immobilized on amorphous silica-alumina, Zeo-Y and ZSM-5, were evaluated as catalysts in the deconstruction of n-hexadecane model substrate with hydrogen to delineate between different mechanisms, i.e., monofunctional- (acid site dominated) or bifunctional-hydrocracking (acid site & metal site) versus hydrogenolysis (metal site dominated), established from the product distributions. The ZSM-5-based catalysts were further studied in the depolymerization of polyethylene. Based on these studies, the catalysts are plotted on an activity-mechanism map that functions as an expandable basis to benchmark catalytic activity and to identify optimal catalysts that afford specific product distributions. The systematic approach reported here should facilitate the acceleration of catalyst discovery for polyolefin depolymerization.
Live-seq enables temporal transcriptomic recording of single cells
Authors: Chen Wanze , Guillaume-Gentil Orane , Rainer Pernille Yde , Gäbelein Christoph G. , Saelens Wouter , Gardeux Vincent , Klaeger Amanda , Dainese Riccardo , Zachara Magda , Zambelli Tomaso , Vorholt Julia A. , Deplancke Bart
Published: August 2022

Single-cell transcriptomics (scRNA-seq) has greatly advanced our ability to characterize cellular heterogeneity1. However, scRNA-seq requires lysing cells, which impedes further molecular or functional analyses on the same cells. Here, we established Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy2,3, thus allowing to couple a cell’s ground-state transcriptome to its downstream molecular or phenotypic behaviour. To benchmark Live-seq, we used cell growth, functional responses and whole-cell transcriptome read-outs to demonstrate that Live-seq can accurately stratify diverse cell types and states without inducing major cellular perturbations. As a proof of concept, we show that Live-seq can be used to directly map a cell’s trajectory by sequentially profiling the transcriptomes of individual macrophages before and after lipopolysaccharide (LPS) stimulation, and of adipose stromal cells pre- and post-differentiation. In addition, we demonstrate that Live-seq can function as a transcriptomic recorder by preregistering the transcriptomes of individual macrophages that were subsequently monitored by time-lapse imaging after LPS exposure. This enabled the unsupervised, genome-wide ranking of genes on the basis of their ability to affect macrophage LPS response heterogeneity, revealing basal Nfkbia expression level and cell cycle state as important phenotypic determinants, which we experimentally validated. Thus, Live-seq can address a broad range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.
Endocytosis in the axon initial segment maintains neuronal polarity
Authors: Eichel Kelsie , Uenaka Takeshi , Belapurkar Vivek , Lu Rui , Cheng Shouqiang , Pak Joseph S. , Taylor Caitlin A. , Südhof Thomas C. , Malenka Robert , Wernig Marius , Özkan Engin , Perrais David , Shen Kang
Published: August 2022

Neurons are highly polarized cells that face the fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly1. The axon initial segment (AIS) is a specialized domain that separates a neuron’s morphologically, biochemically and functionally distinct axon and dendrite compartments2,3. How the AIS maintains polarity between these compartments is not fully understood. Here we find that in Caenorhabditis elegans, mouse, rat and human neurons, dendritically and axonally polarized transmembrane proteins are recognized by endocytic machinery in the AIS, robustly endocytosed and targeted to late endosomes for degradation. Forcing receptor interaction with the AIS master organizer, ankyrinG, antagonizes receptor endocytosis in the AIS, causes receptor accumulation in the AIS, and leads to polarity deficits with subsequent morphological and behavioural defects. Therefore, endocytic removal of polarized receptors that diffuse into the AIS serves as a membrane-clearance mechanism that is likely to work in conjunction with the known AIS diffusion-barrier mechanism to maintain neuronal polarity on the plasma membrane. Our results reveal a conserved endocytic clearance mechanism in the AIS to maintain neuronal polarity by reinforcing axonal and dendritic compartment membrane boundaries.
Spatial profiling of chromatin accessibility in mouse and human tissues
Authors: Deng Yanxiang , Bartosovic Marek , Ma Sai , Zhang Di , Kukanja Petra , Xiao Yang , Su Graham , Liu Yang , Qin Xiaoyu , Rosoklija Gorazd B. , Dwork Andrew J. , Mann J. John , Xu Mina L. , Halene Stephanie , Craft Joseph E. , Leong Kam W. , Boldrini Maura , Castelo-Branco Gonçalo , Fan Rong
Published: August 2022

Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context1. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping2–5, but the ability to capture spatial epigenetic information of tissue at the cellular level and genome scale is lacking. Here we describe a method for spatially resolved chromatin accessibility profiling of tissue sections using next-generation sequencing (spatial-ATAC-seq) by combining in situ Tn5 transposition chemistry6 and microfluidic deterministic barcoding5. Profiling mouse embryos using spatial-ATAC-seq delineated tissue-region-specific epigenetic landscapes and identified gene regulators involved in the development of the central nervous system. Mapping the accessible genome in the mouse and human brain revealed the intricate arealization of brain regions. Applying spatial-ATAC-seq to tonsil tissue resolved the spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology progresses spatial biology by enabling spatially resolved chromatin accessibility profiling to improve our understanding of cell identity, cell state and cell fate decision in relation to epigenetic underpinnings in development and disease.
MYB orchestrates T cell exhaustion and response to checkpoint inhibition
Authors: Tsui Carlson , Kretschmer Lorenz , Rapelius Svenja , Gabriel Sarah S. , Chisanga David , Knöpper Konrad , Utzschneider Daniel T. , Nüssing Simone , Liao Yang , Mason Teisha , Torres Santiago Valle , Wilcox Stephen A. , Kanev Krystian , Jarosch Sebastian , Leube Justin , Nutt Stephen L. , Zehn Dietmar , Parish Ian A. , Kastenmüller Wolfgang , Shi Wei , Buchholz Veit R. , Kallies Axel
Published: August 2022

CD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and by the impaired production of cytokines. This state of restrained functionality—which is referred to as T cell exhaustion1,2—is maintained by precursors of exhausted T (TPEX) cells that express the transcription factor T cell factor 1 (TCF1), self-renew and give rise to TCF1− exhausted effector T cells3–6. Here we show that the long-term proliferative potential, multipotency and repopulation capacity of exhausted T cells during chronic infection are selectively preserved in a small population of transcriptionally distinct CD62L+ TPEX cells. The transcription factor MYB is not only essential for the development of CD62L+ TPEX cells and maintenance of the antiviral CD8+ T cell response, but also induces functional exhaustion and thereby prevents lethal immunopathology. Furthermore, the proliferative burst in response to PD-1 checkpoint inhibition originates exclusively from CD62L+ TPEX cells and depends on MYB. Our findings identify CD62L+ TPEX cells as a stem-like population that is central to the maintenance of long-term antiviral immunity and responsiveness to immunotherapy. Moreover, they show that MYB is a transcriptional orchestrator of two fundamental aspects of exhausted T cell responses: the downregulation of effector function and the long-term preservation of self-renewal capacity.