bluuebunny/crossref_metadata_2025 huggingface dataset:
Consciousness
Authors: Siewert Charles
Published: March 2021

This chapter gives consciousness a central role in value. It begins by showing how we can interpret and defend the idea that many common forms of consciousness are intrinsically beneficial to us—even if we don’t embrace subjectivism about well-being. It then shows how we can rationally accord these benefits such importance that we would find our own continued existence worthless without them. Neither objective list nor desire-satisfactionist views of well-being threaten this result. Moreover, regarding subjects’ desire-satisfaction: we can see that this bears on a non-instrumental concern for them only if they are capable of subjective experience: consciousness makes desires matter morally. Finally, the moral significance of consciousness is further deepened by seeing how our self-expressive experience entitles us to a respect that is due beings who make themselves accountable to norms—and how, since we are such beings, our lives have irreplaceable value.
The Value of Consciousness in Medicine
Authors: O’ Leary Diane
Published: March 2021

generally accept that medicine’s conceptual and ethical foundations are grounded in recognition of personhood. With patients in vegetative state, however, we’ve understood that the ethical implications of phenomenal consciousness are distinct from those of personhood. This suggests a need to reconsider medicine’s foundations. What is the role for recognition of consciousness (rather than personhood) in grounding the moral value of medicine and the specific demands of clinical ethics? I suggest that, according to holism, the moral value of medicine is secured when conscious states are recognized in everyday medical science. Moreover, consciousness fully motivates traditional principles of clinical ethics if we understand respect for autonomy as respect for the dominion of an experiencer in the private, inescapable realm of bodily experience. When medicine’s foundations are grounded in recognition of consciousness, we understand how patients fully command respect even when they lack capacity to exercise their bodily dominion through decision-making.
Arthur Rimbaud
Authors: Hofmann Michael
Published: March 2021

The chapter presents a reading of probably the most celebrated ship-poem in existence, written exactly one hundred and fifty years ago by a teenaged boy in provincial France who had never seen the sea. The poem, in which the boat ‘speaks’, is read as unusually brilliant homework, as autobiography, as showing-off, as prophecy, as an account of empire. The Pyrrhic continuance or persistence of the drowning boat is read as an image of literature itself.
Structure and Nomenclature
Authors: Simester A P
Published: March 2021

This chapter discusses criminal law’s structure and working doctrines, offering some preliminary remarks about how the major legal doctrines relate to the principles identified in the previous chapter. In terms of the basic framework, it is conventional these days for common lawyers to divide up the law of crimes into three rather broad groupings: actus reus (the so-called ‘external’ or ‘physical’ elements of the crime); mens rea (the defendant’s mental state or, sometimes, the lack of it); and defences. The master question for criminal liability then becomes one of concurrence—is there a moment in time at which the actus reus and mens rea requirements of the offence are simultaneously satisfied, and there are no defences available? However, this threefold division is not clean, and the contents of each part are not independent of one another. The chapter presents a rough structural sketch of the criminal law.
The end of the beginning?
Authors: Allen John R. , Hodges F. Ben , Lindley-French Julian
Published: March 2021

What are the specific lessons of Europe’s contemporary history for its future defence and how does history illuminate the challenges of such a defence? From D-Day to the creation and development of NATO, the importance of sufficient and legitimate military power has been at the heart of credible defence and deterrence. Innovation and technology allied to strategic responsibility have been key to maintaining the unity of effort and purpose vital to upholding and expanding Europe’s freedoms. Ultimately, for Europe’s defence to be credible to its citizens as well as adversaries and allies, there must be a tight bond between defence, power, and leadership allied to structures that magnify security and defence, such as NATO and the EU. There must also be a demonstrable sharing of equitable burdens without which any defence effort withers and dies over time.
He Will Wash His Garments in Wine (Gen 49:11)
Authors: Quick Laura
Published: March 2021

This chapter takes its starting point from the notion that, for the biblical authors, clothing and jewellery symbolically encoded the personhood of its wearer. These items could thus manifest and modify the body in ritual contexts. As such, the manipulation and destruction of clothing items in the ritual context took on a heavy symbolic value. After the ritual use of textiles in the wider ancient Near East is explored, this insight is shown to explicate a number of the more difficult references to clothing in biblical literature. Moreover, since the production of textiles was gendered in the ancient world, this special function of clothing provided women with agency in ritual and religious settings. In these texts, textiles afford women with the means to become experts in rituals associated with life and death. These references therefore attest to the use of clothing and textiles in an important but largely unacknowledged aspect of female ritual expertise.
Rethinking the Islamic Republican Canon
Authors: Shams Fatemeh
Published: March 2021

The opening chapter tackles the problematic aspects of literary canonization, with specific reference to the complex process of literary de-canonization and re-canonization in the wake of 1979 revolution. It introduces, for the first time, the work and lives of two generations of poets who belong to the Islamic Republic’s canon of poetry, their approach to, and relationship with, the Persian poetic tradition. The reader thus begins the book grounded in the foundations of a poetic trend in modern Iran that was sponsored and promoted by the establishment following the 1979 revolution. While introducing the ‘key figures’ of the Islamic Republic’s official canon of poetry, the chapter throws light on the complex and multilayered process of reshaping the pre-revolutionary poetry canon in years preceding and following the 1979 revolution
A War to Remember (2)
Authors: Shams Fatemeh
Published: March 2021

As the war continued, and the death toll grew, some official poets began to engage with the conflict through greater degrees of realism. This chapter examines this aspect, and the ensuing complications in the relationship between poetry and the state, to present a nuanced, more complex portrait of the diversity of official war poetry. By drawing on other war literary traditions, such as English poetry during the First World War, this chapter aims to shed light on the ways in which the official poets of the Islamic Republic symbolized their emotional responses to war, depravation and trauma.
Inventing a Courtly Tradition
Authors: Shams Fatemeh
Published: March 2021

The final chapter of this book aims to theorize the current dialectics of conformist poetry and power in Iran. By focusing on the ceremonial aspects of this relationship, the chapter introduces and analyzes the annual poetry nights established by the new leader, Ali Khamenei, whose ascension into power has been marked by ongoing episodes of political anxiety and ideological instability. Official poetry under Khamenei has been brought into the center of state operations; this chapter explores the reasons behind this, and the ways in which its ideological importance has been cemented by the current political administration in Iran. The chapter brings the book to a close by arguing that Khamenei’s plight for political legitimacy has been one of the main factors behind his strategy of inventing a new poetic tradition.
Origins and Telos
Authors: Larsen Signe Rehling
Published: March 2021

Why do states federate? This chapter argues that states constitute federal unions because they are incapable of maintaining their own political autonomy and existence. The main reasons for this are a military threat or because the states need to govern and have access to larger internal markets. In order to perpetuate the political autonomy of its Member States, a federation is therefore concerned with defence and/or economic government. After WWII, with the collapse of the fascist experiments and the decline of the European maritime empires, most European states were faced with a long overdue crisis and were incapable of securing their most basic aims. European integration is an integral part of the post-WWII reconstitution of Europe and a response to this crisis. Proposals for both ‘defence federation’ and ‘economic federation’ were launched after WWII; only the latter was successfully established with the Treaty of Rome.
A German Model? KfW, Field Dynamics, and the Europeanization of “Promotional” Banking
Authors: Mertens Daniel
Published: March 2021

This chapter examines the evolution of Germany’s Kreditanstalt für Wiederaufbau (KfW) within the EU. Presenting KfW as a key pillar of the German economic model that depends on export-led growth, the chapter traces the imprint that Europe’s largest NDB has left on the European field. Beginning in the 1990s, when the bank counseled and funded development banks in 14 transition countries in CEE countries, KfW became the first incumbent of the emerging field. Adapting itself to the incentives and constraints stemming from European integration during the 2000s, it continues to shape the field today with both the assertiveness of its financial firepower and business model, and the rationale of the reluctant but embedded hegemon that Germany is in the European Union.
Privatization, Crisis, and the Transformation of Cassa Depositi e Prestiti
Authors: Bulfone Fabio , Carlo Donato Di
Published: March 2021

This chapter explores the transformation of Cassa Depositi e Prestiti (CDP) from a small Directorate-General within the Treasury to a full-fledged National Development Bank charged with channeling credit toward small firms and Mid-Caps, financing infrastructural projects, providing patient liquidity to the Treasury and equity investment to strategic firms. After a brief historical excursus, the chapter focuses in particular on two watershed moments in the history of CDP: the privatization in 2003 and the sovereign debt crisis. Both junctures paved the way to a substantial expansion and diversification of CDP’s activities in support of the Italian economy. Italy provides an ideal vantage point to explore the relationship between NDBs and their sovereigns due to the unique mismatch between the financial strength of CDP, funded by postal savings, and the financial needs of the cash-stripped Italian sovereign, burdened by an enormous public debt.
Managing the Contradictions of Development Finance in the EU’s Eastern Periphery
Authors: Piroska Dóra , Mérő Katalin
Published: March 2021

Eastern members of the European Union have turned to development banks only to a limited extent so far. In this chapter, in order to understand why the “development imagination” of Eastern governments remained restricted, we look at the underlying logics of the national development finance fields. Through the case studies of Hungary and Poland, we uncover marked contradictions within the fields. Initially, development finance was torn between the contradictory logics of neoliberalism and developmentalism, followed by institution-building efforts from the EU that resulted in functioning development banks designed primarily for the EU’s Single Market. Finally, when financial nationalist and authoritarian political parties came to power, development banks came under firm political control, while new development actors appeared. Development banks in Hungary and Poland also exhibit differences in size, structure, and focus that we trace over time. In the end, we argue that today Eastern development banks’ ability to connect, contribute, and benefit from EU structures shows a marked difference from core Member States, one which calls for change in the EU development institutions and policies.
Introduction
Authors: Perrone Nicolás M.
Published: March 2021

The role of the business leaders, bankers, and lawyers who promoted investment treaties and ISDS in the post-World War II period remains controversial. The introductory chapter argues that these norm entrepreneurs and their professional associations created a legal imagination about foreign investment relations which remains alive and well in both international investment law and ISDS awards. Their contribution to the progressive development of the law consisted of ideas as much as practice, particularly the way in which they collated their ideas into a vision of foreign investment relations. The chapter introduces the main features of this legal imagination, including the relevance of certain interpretations of property and contracts. It claims that grasping this imagination calls for a transnational law method, and concludes with an overview of the book.
Framing the Question
Authors: Schapiro Tamar
Published: March 2021

In this chapter, I frame my question. My explicandum is the moment in which you are inclined, but not thereby determined, to φ. I call this “the moment of drama.” I want to know what challenges and opportunities we are faced with, in this moment. My question arises out of a distinctive philosophical method, one that differs from the standard method in philosophy of mind and action. The standard method asks, “what happens when someone acts?” My method, which is inspired by Kant, asks, “what am I doing, insofar as I am acting?” I explain how this method leads me to take the moment of drama as my explicandum. Finally, I preview three features of the relation between inclination and will that characterize this moment: being inclined to φ is a non-voluntary condition that exerts asymmetric pressure on the will, while also playing a deliberative role.
The Brute Force View
Authors: Schapiro Tamar
Published: March 2021

In this chapter, I consider a conception of inclination that haunts the theory of action. It is alluded to in metaphors, but it is almost never defended systematically. This “brute force view” holds that our relation to our inclinations is analogous to our relation to external, brute forces. The intuitive appeal of this view is that it seems to capture two features of the way our inclinations influence us: they exert asymmetric pressure on us, and they are non-voluntary. But it does not capture a third feature, namely the deliberative role inclinations play. I claim further that upon closer inspection, the brute force view does not, in fact, adequately capture the first two features. The reason is that the brute force view makes inclinations external to us, in the wrong way. It makes being inclined to φ too unlike φ-ing.
The Inner Animal View
Authors: Schapiro Tamar
Published: March 2021

In this chapter, I put forward the core of my “inner animal” view. When you are inclined but not determined to φ, you are relating to a part of yourself that has already determined itself to φ. This part of you as the structure of a creature of instinct. I find a suggestion of this view in Kant’s idea that what necessitates the arbitrium brutum merely affects the arbitrium sensitivum liberum. I develop the idea by relying on Korsgaard’s conception of animal agency. When you are in the moment of drama, I claim, part of you is already active, under the guidance of the instinctive part of your mind, while the rest of you has not yet determined itself to act. You are “drawn out of yourself.” I then address initial worries about my view, namely that it is objectionably dualistic, metaphorical, or biological.
The Role of ‘Fundamental Attunement’ in The Fundamental Concepts of Metaphysics
Authors: Cykowski Beth
Published: March 2021

This chapter proceeds chronologically through the lectures and examines Heidegger’s analysis in Part One of The Fundamental Concepts of Metaphysics of the ‘fundamental attunement’ of ‘profound boredom’, which he regards as the contemporary optic through which all metaphysics occurs, including that of the human/animal distinction. The chapter introduces Heidegger’s argument that the concept of a metaphysical abyss between human and animal is the expression of a deep-seated inherited prejudice concerning a division between ‘life’ and ‘spirit’. This division is crystallised in the work of contemporary philosophers of culture, including Oswald Spengler, Ludwig Klages, Max Scheler, and Leopold Ziegler, all of whom Heidegger regards as ‘spokespeople’ of the contemporary epoch. The chapter examines Heidegger’s engagement with these thinkers, followed by his conclusion that their work signals a profound boredom gripping the age.
Introduction
Authors: Stojnić Una
Published: March 2021

The chapter provides an introduction to the key themes of the book. It introduces the problem of context-sensitivity, and its theoretical significance. It then outlines the key elements of the account the book develops—the notion of context, of content, and of context-content interaction—situating them with respect to the dominant tradition in theorizing about context-sensitivity. The chapter, finally, outlines some of the philosophical ramifications of this account and of its criticism of the traditional model for the nature of context, content, and their interaction. The book argues that the traditional model of context-sensitivity underlies the linguistic arguments for non-propositional accounts of content and non-classical semantics that have gained support in recent literature. But it is the traditional model that should be abandoned instead, and replaced with a more adequate linguistic model of context this book develops.
Content in Context
Authors: Stojnić Una
Published: March 2021

On the traditional picture, sentences express content relative to context. This content then is, or determines, truth-conditional, propositional content, which is what we assert and believe, and which can guide our action. If I have a thought about the world, and I want to convey it to you, I should utter a sentence which, in this context, expresses that thought. You can then understand it, and come to believe it, and it might guide your action. But on the current proposal the context is constantly changing, even mid-utterance, and utterances are interpreted as instructions to update the context. What of our simple account of thought, communication, and action? This chapter shows our dynamic account still delivers propositional content. While utterances are semantically assigned dynamic meaning, this meaning serves as an instruction to build ordinary propositional content.
The Entrepreneurial Widows of 1 Timothy
Authors: Maier Harry O.
Published: March 2021

This chapter continues a focus on the Christian Bible with examination of ‘The Entrepreneurial Widows of 1 Timothy’. It argues that the exhortations and admonitions to widows (i.e. unmarried women) voiced in 1 Timothy—identified as a highly rhetorical pseudonymous letter written in Paul’s name—attests to a concern with single women’s patronage of Christ assemblies, which the writer seeks to address by having them marry. The contributor seeks to move beyond a common explanation that the letter was occasioned by ascetical teachings in which women discovered in sexual continence a new freedom from traditional gender roles. The chapter aims to establish that the letter has a broader economic concern with widows, through an historical exploration of the socio-economic status of women who were artisans in the imperial urban economy. It identifies the means by which women gained skill in trades, the roles they played in the ‘adaptive family’ in which households of tradespeople plied their trade often at economic levels of subsistence. New Testament texts point to artisan women, some of them probably widows, who played important roles of patronage and leadership in assemblies of Christ followers. By attending to levels of poverty in the urban empire, traditional views of the widows of 1 Timothy as wealthier women assigned to gender roles are seen in a new light through consideration of spouses accustomed to working alongside their husbands and taking on the businesses after they died. While the lives of these women are largely invisible, attention to benefactions of wealthy women to synagogues and associations gives insight into the lives of women acting independently in various kinds of social gatherings.
Women Office Holders in Montanism
Authors: Tabbernee William
Published: March 2021

The volume then moves to the evidence of the Montanists in Phrygia. This chapter explores the role of women as invested with religious authority, leaders, prophets, ordained, and objects of reverence in Montanist communities, in the light both of literary sources and epigraphic evidence. It considers key issues, for example whether the designation presbytera on the tombstone of Ammion in ancient Temenothyrai, now Uşak, Turkey, means ‘elderly woman’, ‘the wife of a presbyter (or bishop)’, or a ‘female presbyter’. In the latter case, was this title simply honorific or involve holding of an actual office? It decides ultimately this was an actual office for a woman that functioned in an entirely Catholic community, perhaps in a proto-Catholic house-church at Temenothyrai, influenced by the attested practices of the Montanists. The Montanists, founding their gender theory on Paul’s assertion in Gal. 3:28 (so Epiphanius, Panarion 49.2.5), rejected the dichotomy of public and private spheres for the ministry of men and women, and women were included as office holders serving both.
Women Deacons in Ancient Christian Communities
Authors: Wijngaards John
Published: March 2021

This chapter considers ‘Women Deacons in Ancient Christian Communities: Leadership and Ordination’. Women deacons are widely attested in the Greek-speaking Catholic East during the first millennium. Ancient rites that have been preserved show that the ordination of women deacons was truly ‘sacramental’, just as that of male deacons. Their role consisted in instructing and baptizing female catechumens, guiding women at Sunday worship, taking communion to the sick, and ministering at funeral services. They belonged to the clergy in virtually every parish. They enjoyed more or less the same legal status as male deacons. As time passed, however, the female diaconate was relinquished, partly because of the diminishing of adult baptisms, partly on account of growing anxiety about female clergy possibly polluting the altar through menstruation.
Women Church Leaders in and around Fifth-century Rome
Authors: Kateusz Ally , Confalonieri Luca Badini
Published: March 2021

This chapter considers artistic representations, showing evidence of ‘Women Church Leaders in and around Fifth-century Rome’. It focuses on two artefacts that portrayed women church leaders operating in this broad context. It addresses frescoes of deceased women painted with open gospel books in the San Gennaro Catacombs in Naples; it proposes that the most logical interpretation of the iconographic motifs associated with them is that they were women bishops, perhaps two of the women about whom Pope Gelasius complained to male bishops in southern Italy c.496. For cultural context it next considers an ivory reliquary box discovered in 1906, which depicts three pairs of men and women in the altar area of Old St Peter’s Basilica in Rome. This scene has recently been re-analysed; one of the pairs appears to have been sculpted jointly officiating the Eucharist at the basilica’s altar. Additional fifth- and sixth-century artefacts that portray women as clergy, sometimes paired with men, sometimes independently, affirm both the identification of women bishops in the two Naples catacomb frescoes and also the scene of the woman and man officiating at the altar in Old St Peters on the ivory box.
Public Authority Liability in Hungary
Authors: Berkes Lilla
Published: March 2021

In Hungary, government liability in tort was affected by the constitutional change that occurred after 1989. A new provision clearly stating government liability replaced the old one. A public body that acts unlawfully and causes damages to others is thus liable in tort, just like any private individual would be. Moreover, judicial review is no longer conceived as an extraordinary remedy. However, substantively, the basic premise is not that illegality in itself will give rise to damages liability, especially when the administration exercises discretionary powers. Moreover, the claimant must bring an administrative appeal before a judicial remedy is available. These appeals have been partially reshaped by the new Administrative Procedure Act (2018), which is important also for the procedural requirements it sets out with regard to the discharge of administrative functions and powers. Both EU law and the European Convention on Human Rights are increasingly relevant in this respect.
The Liability of Public Administration
Authors: Cortese Fulvio
Published: March 2021

At the end of the nineteenth century, Italian courts constructed government liability in narrow terms, excluding it whenever government took acts of imperium. Article 28 of the Constitution deviates from that line of cases, because it lays down two principles: first, that the officials and employees of public bodies are directly liable for acts committed in violation of rights and, second, that in such cases civil liability extends to public bodies. Concretely, the standard governing the non-contractual liability of public bodies is influenced by the rules of the Civil Code. Liability can thus be based on the existence of a breach of existing legal rules, including procedural constraints on the exercise of administrative powers. For example, the unlawful issuing of a building permit gives rise to liability. However, when public authorities exercise real discretion, issues of liability will be treated differently. And, unlike other legal systems, such issues often fall within the competence of administrative courts.
International Courts in Latin America and the Caribbean
Authors: Caserta Salvatore
Published: March 2021

This introductory chapter presents the main theoretical and methodological issues of the book. In terms of theory, the chapter explains that the book relies on the concept of de facto authority, according to which international courts become authoritative and powerful when their rulings are endorsed by relevant audiences in their practices. To complement this approach, the chapter explains that the book proposes five original analytical markers, which are central for analysing and explaining the social processes through which international courts, in general, and regional economic courts, in particular, gain or lose de facto authority. These are: (i) the nature of the political environment surrounding them; (ii) the timing of their institutional founding; (iii) the material and/or abstract interests of the agents interacting with them; (iv) the fundamental support of different social groups relating to them; and (v) the societal embeddedness in their operational context.
The Extended Foundation of the Central American Court of Justice between Pacification and Globalisation
Authors: Caserta Salvatore
Published: March 2021

This chapter deals with the extended process of creation of the Central American Court of Justice (CACJ) arguing that, similar to the Caribbean Court of Justice (CCJ), the Court is also the institutional crystallisation of the different movements that characterised the Central American legal field over time. One of the movements leading to the creation of the CACJ is highlighted in the literature on the proliferation of international courts (ICs), according to which the Court is an EU-style regional economic court whose aim is to enforce the policies of the Central American Integration System (SICA). The other movement, pursued by more local elites, is concerned with the long-lasting project of pacifying and democratising the region by legal and judicial means. In addition to examining the dynamics at play during this extended foundation, this chapter also looks at the window of opportunity that led to the creation of the Court, which was found in the Esquipulas I and II peace negotiations and the need to strengthen economic integration at the end of the Cold War.
Status
Authors: Nichols Shaun
Published: March 2021

Moral judgments are often regarded as universally true, whereas judgments of taste are taken to be only true relative to some group or individual. How could such meta-evaluative assessments be acquired? This chapter argues that people use consensus information to arrive at such assessments, and that it is rational to do so. Statistical inference mandates a trade-off between the extent to which a hypothesis fits the data, and the extent to which the hypothesis is flexible in its ability to fit a wider range of data. If almost everyone agrees in their judgments, this provides some reason to endorse a universalist hypothesis, according to which there is a single fact that the majority is tracking. So if almost everyone thinks that a certain action is wrong, the high consensus provides some evidence that it’s a universal truth that this action is wrong. The inference that it’s a universal truth that an action is wrong can also ground the judgment that the action is wrong in a way that is independent of authority. Thus, this might also provide an explanation for the acquisition of the moral/conventional distinction.
Introduction
Authors: Lamas Carmen E.
Published: March 2021

In May of 1892, the Cuban exile Nestor Ponce de León (1837–99) delivered a lecture titled “Los primeros poetas de Cuba” (1892, 385) (The First Cuban Poets) at a meeting of the Sociedad de Literatura Hispano-Americana in New York City. Despite the name of the society and the ostensible focus of Ponce de León’s talk, this meeting was not simply a gathering of friends and visiting authors from Latin America who found themselves in the vicinity of New York and who happened to love Cuban literature and the wider culture of belle lettres in the Americas. Ponce de León was surrounded by fellow exiles planning revolution. In the audience sat one of the founders and a former president of the Sociedad, José Martí (1853–95), who had stepped down from leading the New York literary society in order to organize the Partido Revolucionario Cubano. As was so often the case among nineteenth-century Latina/o intellectuals (and their Latin American counterparts), literary and political practices were mutually informing and hard to separate into neat categories of their own....
The effects of the BAILAMOS Dance Program on hippocampal volume in older Latinos: a randomized controlled pilot study
Authors: Guzman Jacqueline , Aguiñaga Susan , Balbim Guilherme M , Lamar Melissa , Marques Isabela G , Marquez David X
Published: March 2021

Hippocampal atrophy is associated with cognitive decline. Physical activity (PA) can reverse the hippocampal loss. This study investigated the effects of the 4 month BAILAMOS dance program on hippocampal volume and self-reported PA in Latinos. Participants were randomized to the BAILAMOS dance program or waitlist control group (N = 14, n = 10 intervention, n = 4 waitlist, 67 ± 6.1 years old, 70% female). Hippocampal volumes were derived from Magnetic Resonance Imaging whole-brain T1-weighted images. Participants self-reported PA through the Community Healthy Activities Model Program for Seniors Physical Activity Questionnaire for older adults. There were no statistically significant changes in hippocampal volume preintervention to postintervention (F[1, 8] = .077, p = .79, d = .05) and no associations between PA change and hippocampal volume (F[4, 13] = .71, p = .61). However, dance participants self-reported more PA (d = .54) compared to the control. These findings demonstrate that the BAILAMOS dance program did not decrease hippocampal atrophy; however, it increased self-reported PA. Future studies should include longer and more cognitively demanding interventions to determine whether dance can reduce cognitive decline through hippocampal changes.
ATP5B promotes the metastasis and growth of gastric cancer by activating the FAK/AKT/MMP2 pathway
Authors: Wang Xufeng , Chang Xinyu , He Changyu , Fan Zhiyuan , Yu Zhenjia , Yu Beiqin , Wu Xiongyan , Hou Junyi , Li Jianfang , Su Liping , Liu Bingya , Zhu Zhenggang
Published: March 2021

Adenosine triphosphate (ATP) in the tumor microenvironment serves a vital role during tumor progression. ATP synthase F1 β subunit (ATP5B) is one of the most important subunits of ATP synthase and increases cellular ATP levels. ATP5B reportedly participates in carcinogenesis in several tumors. However, the regulatory mechanisms of ATP5B remain poorly understood in gastric cancer (GC). Here, we determined that high ATP5B expression in tumor tissues of GC is positively correlated with age, the tumor size, the TNM stage, lymph node metastasis, and patients’ poor prognosis. The overexpression of ATP5B in GC cells elevated the cellular ATP content and promoted migration, invasion and proliferation. The levels of MMP2 expression, phosphorylated FAK, and phosphorylated AKT were increased after ATP5B overexpression in GC cells. Additionally, ATP5B overexpression increased the extracellular ATP level through the secretion of intracellular ATP and activated the FAK/AKT/MMP2 signaling pathway. ATP5B‐induced downstream pathway activation was induced through the plasma membrane P2X7 receptor. Inhibitors of P2X7, FAK, AKT, and MMP2 suppressed the proliferative, migratory, and invasive capabilities of GC cells. In conclusion, our experiments indicate that ATP5B contributes to tumor progression of GC via FAK/AKT/MMP2 pathway. ATP5B, therefore, may be a biomarker of poor prognosis and a potential therapeutic target for GC.
ArfGAP1 acts as a GTPase‐activating protein for human ADP‐ribosylation factor‐like 1 protein
Authors: Feng Hsiang‐Pu , Cheng Hsiao‐Yun , Hsiao Ting‐Feng , Lin Tai‐Wei , Hsu Jia‐Wei , Huang Lien‐Hung , Yu Chia‐Jung
Published: March 2021

ADP‐ribosylation factors (Arfs) and Arf‐like (Arl) GTPases are key regulators of intracellular vesicle trafficking and Golgi structure. Both Arf and Arl proteins cycle between active GTP‐bound and inactive GDP‐bound forms, where guanine nucleotide exchange factors (GEFs) regulate the exchange of GDP for GTP, whereas GTPase‐activating proteins (GAPs) promote the hydrolysis of bound GTP. Human Arl1 is located at the trans‐Golgi network (TGN) and regulates the function and structure of the Golgi complex. However, neither GEFs nor GAPs for human Arl1 have been identified. Here, we report that ArfGAP1, an Arf1 GAP, can promote GTP hydrolysis of Arl1. We show that ArfGAP1 directly interacts with GTP‐bound Arl1 and exhibits GAP activity toward Arl1 in vitro. Exogenous expression of ArfGAP1, but not ArfGAP2 and ArfGAP3, causes dissociation of endogenous Arl1 from the TGN. In addition, GAP activity‐deficient ArfGAP1 fails to regulate the Golgi localization of Arl1. Using an activity pull‐down assay, we demonstrated that ArfGAP1 regulates the levels of Arl1‐GTP in cells expressing ArfGAP1‐myc or with ArfGAP1 knockdown. Finally, we observed that, similar to expression of putative active Arl1 (Arl1QL), ArfGAP1 knockdown impairs endosome‐to‐TGN retrograde transport of the Shiga toxin B‐subunit. Thus, our findings support the idea that ArfGAP1 acts as an Arl1 GAP to regulate the function of Arl1 in vesicle trafficking at the TGN.
Lb2Cas12a and its engineered variants mediate genome editing in human cells
Authors: Liu Xiaoyu , Lin Li , Tang Lianchao , Xie Haihua , Gu Lingkai , Lv Xiujuan , Liu Changbao , Zhao Junzhao , Deng Ruzhi , Liu Yong , Qu Jia , Gu Feng
Published: March 2021

Cas12a‐mediated targeted genome engineering strategies have enabled a broad range of research and clinical applications. However, the limited target‐selection spectrum and low activity/fidelity remain a bottleneck for its widespread application in precision site‐specific human genome editing. Therefore, there exists an acute need to identify novel Cas12a nucleases with improved features for genome editing. By screening a range of candidate Cas12a nucleases, here we demonstrate that Lb2Cas12a possesses genome editing activity in human cells and it has greater flexibility in PAM (5ʹ‐BYYV‐3ʹ) selection. Furthermore, we engineered Lb2Cas12a to generate variants (Lb2Cas12a‐RVR and Lb2Cas12a‐RR), which greatly expands the target‐selection spectrum. Our study illustrated that Lb2Cas12a could be harnessed as additional genome editing tool for the manipulation of human genome.
Downregulation of miR‐497‐5p prevents liver ischemia‐reperfusion injury in association with MED1/TIMP‐2 axis and the NF‐κB pathway
Authors: Wu Kun , Tao Guoquan , Xu Ting , An Yuanyuan , Yu Xiangyou , Wang Yi , Wang Shaochuang , Guo Wen , Ma Long
Published: March 2021

Liver ischemia‐reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR‐497‐5p in liver I/R injury in mice. The related regulatory factors of miR‐497‐5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin‐eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme‐linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR‐497b‐5p was increased in liver I/R injury. Knockdown of miR‐497b‐5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR‐497b‐5p could activate the nuclear factor kappa‐B (NF‐κB) pathway by inhibiting the MED1/TIMP‐2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.
The “Matrisome” reveals the characterization of skin keloid microenvironment
Authors: Zhang Shikun , Liu Binghui , Wang Wenjuan , Lv Luye , Gao Dunqin , Chai Mi , Li Mansheng , Wu Zhihong , Zhu Yunping , Ma Jie , Leng Ling
Published: March 2021

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large‐scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM‐associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.
The energy sensor AMPK orchestrates metabolic and translational adaptation in expanding T helper cells
Authors: Mayer Katharina A. , Smole Ursula , Zhu Ci , Derdak Sophia , Minervina Anastasia A. , Salnikova Maria , Witzeneder Nadine , Christamentl Anna , Boucheron Nicole , Waidhofer‐Söllner Petra , Trauner Michael , Hoermann Gregor , Schmetterer Klaus G. , Mamedov Ilgar Z. , Bilban Martin , Ellmeier Wilfried , Pickl Winfried F. , Gualdoni Guido A. , Zlabinger Gerhard J.
Published: March 2021

The importance of cellular metabolic adaptation in inducing robust T cell responses is well established. However, the mechanism by which T cells link information regarding nutrient supply to clonal expansion and effector function is still enigmatic. Herein, we report that the metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK) is a critical link between cellular energy demand and translational activity and, thus, orchestrates optimal expansion of T cells in vivo. AMPK deficiency did not affect T cell fate decision, activation, or T effector cell generation; however, the magnitude of T cell responses in murine in vivo models of T cell activation was markedly reduced. This impairment was global, as all T helper cell subsets were similarly sensitive to loss of AMPK which resulted in reduced T cell accumulation in peripheral organs and reduced disease severity in pathophysiologically as diverse models as T cell transfer colitis and allergic airway inflammation. T cell receptor repertoire analysis confirmed similar clonotype frequencies in different lymphoid organs, thereby supporting the concept of a quantitative impairment in clonal expansion rather than a skewed qualitative immune response. In line with these findings, in‐depth metabolic analysis revealed a decrease in T cell oxidative metabolism, and gene set enrichment analysis indicated a major reduction in ribosomal biogenesis and mRNA translation in AMPK‐deficient T cells. We, thus, provide evidence that through its interference with these delicate processes, AMPK orchestrates the quantitative, but not the qualitative, manifestation of primary T cell responses in vivo.
Maternal high‐salt diet during pregnancy impairs synaptic plasticity and memory in offspring
Authors: Ge Qian , Hu Xiaoxuan , Ma Ning , Sun Meiqi , Zhang Liyun , Cai Zhenlu , Tan Ruolan , Lu Haixia
Published: March 2021

Excess salt intake harms the brain health and cognitive functions, but whether a maternal high‐salt diet (HSD) affects the brain development and neural plasticity of offspring remains unclear. Here, using a range of behavioral tests, we reported that the offspring of maternal HSD subjects exhibited short‐ and long‐term memory deficits, especially in spatial memory in adulthood. Moreover, impairments in synaptic transmission and plasticity in the hippocampus were observed in adult offspring by using in vivo electrophysiology. Consistently, the number of astrocytes but not neurons in the hippocampus of the offspring from the HSD group were significantly decreased, and ERK and AKT signaling pathways involved in neurodevelopment were highly activated only during juvenile. In addition, the expression of synaptic proteins decreased both in juvenile and adulthood, and this effect might be involved in synaptic dysfunction. Collectively, these data demonstrated that the maternal HSD might cause adult offspring synaptic dysfunction and memory loss. It is possibly due to the reduction of astrocytes in juvenile.
Elevated HB‐EGF expression in neural stem cells causes middle age obesity by suppressing Hypocretin/Orexin expression
Authors: Xiang Jinnan , Zhang Shaoyang , Xu Ruiyao , Chu Hongshang , Biswas Soma , Yu Shuxiang , Miao Dengshun , Li Weidong , Li Shentian , Brown Andrew J. , Yang Hongyuan , Xu Yuhong , Li Baojie , Liu Huijuan
Published: March 2021

Obesity is common in the middle aged population and it increases the risks of diabetes, cardiovascular diseases, certain cancers, and dementia. Yet, its etiology remains incompletely understood. Here, we show that ectopic expression of HB‐EGF, an important regulator of neurogenesis, in Nestin+ neuroepithelial progenitors with the Cre‐LoxP system leads to development of spontaneous middle age obesity in male mice accompanied by hyperglycemia and insulin resistance. The Nestin‐HB‐EGF mice show decreases in food uptake, energy expenditure, and physical activity, suggesting that reduced energy expenditure underlies the pathogenesis of this obesity model. However, HB‐EGF expression in appetite‐controlling POMC or AgRP neurons or adipocytes fails to induce obesity. Mechanistically, HB‐EGF suppresses expression of Hypocretin/Orexin, an orexigenic neuropeptide hormone, in the hypothalamus of middle aged Nestin‐HB‐EGF mice. Hypothalamus Orexin administration alleviates the obese and hyperglycemic phenotypes in Nestin‐HB‐EGF mice. This study uncovers an important role for HB‐EGF in regulating Orexin expression and energy expenditure and establishes a midlife obesity model whose pathogenesis involves age‐dependent changes in hypothalamus neurons.
A Dynamic Risk Management Approach for Reducing Harm From Invasive Bedside Procedures Performed During Residency
Authors: Warm Eric J. , Ahmad Yousef , Kinnear Benjamin , Kelleher Matthew , Sall Dana , Wells Andrew , Barach Paul
Published: March 2021

Internal medicine (IM) residents frequently perform invasive bedside procedures during residency training. Bedside procedure training in IM programs may compromise patient safety. Current evidence suggests that IM training programs rely heavily on the number of procedures completed during training as a proxy for resident competence instead of using objective postprocedure patient outcomes. The authors posit that the results of procedural training effectiveness should be reframed with outcome metrics rather than process measures alone. This article introduces the as low as reasonably achievable (ALARA) approach, which originated in the nuclear industry to increase safety margins, to help assess and reduce bedside procedural risks. Training program directors are encouraged to use ALARA calculations to define the risk trade-offs inherent in current procedural training and assess how best to reliably improve patient outcomes. The authors describe 5 options to consider: training all residents in bedside procedures, training only select residents in bedside procedures, training no residents in bedside procedures, deploying 24-hour procedure teams supervised by IM faculty, and deploying 24-hour procedure teams supervised by non-IM faculty. The authors explore how quality improvement approaches using process maps, fishbone diagrams, failure mode effects and analyses, and risk matrices can be effectively implemented to assess training resources, choices, and aims. Future research should address the drivers behind developing optimal training programs that support independent practice, correlations with patient outcomes, and methods that enable faculty to justify their supervisory decisions while adhering to ALARA risk management standards.