bluuebunny/crossref_metadata_2025 huggingface dataset:
Desecuritizing Strangeness
Authors: Vaughan-Williams Nick
Published: June 2021

Chapter 6 recovers vernacular counter-narratives of the border and alternative border imaginaries at work in citizens’ conversations. Beyond dominant narratives of crisis, securitization, abjection, and control, the analysis shows how some vernacular accounts mobilized border logics that questioned portrayals of obsessive walling practices as immutable and inevitable and thus disrupted elite scripts of the ‘crisis’. It is argued that another reason why populist calls to ‘take back control’ flourished despite augmented border security is that actually existing alternative imaginaries among citizens were subjugated in wider public discourse. The discussion begins by recalling the ‘affective atmospheres of welcoming’ that swept across the EU during the summer of 2015. While some vernacular narratives arguably perpetuated a problematic politics of pity akin to many elite governmental narratives of humanitarian crisis, others made arguments about EU citizens’ duties to new arrivals based on a politics of equality and/or of an awareness of the legacies of European colonialism. From here, the analysis considers a range of vernacular narratives that in various ways challenged the notion that there is ‘no alternative’ to tougher deterrent border security and walling. Finally, the chapter mines citizens’ vernacular narratives that do not start with abstract arguments about ‘borders’ at all. In such narratives we find glimpses of what Kristeva (1991) refers to as an ‘ethics of strangeness’: refusals of sovereign mastery of control, the fantasy of ontological security, and the desire to be ‘bordered’. This disrupts the grip of the dominant elite ‘crisis’ narrative and offers new grounds to engage the challenges wrought by increased arrivals and deaths at sea.
Violence, Sovereignty, and the Uganda Police Force
Authors: Tapscott Rebecca
Published: June 2021

How does the Ugandan state produce and sustain the perception among citizens that it commands overwhelming violence? Through a study of the Uganda Police Force, this chapter examines four elements that blur the distinction between lawful and exceptional violence: first, institutional fragmentation obscures the source of violence and undermines accountability; second, the militarization of state and society confuses who can legally purvey violence on behalf of the state; third, the regime engineers law to mask exceptional acts of state violence as lawful; and finally, spectacular and public acts of violence, such as elite assassinations, create widespread speculation about and fear of exceptional state violence. As a result, state violence is unpredictable both in its intensity and its accountability. The manipulation of the relationship between lawful and exceptional violence produces and sustains both fear and hope, making it difficult for ordinary citizens to manage or ignore the possibility of state intervention.
Whither the State?
Authors: Tapscott Rebecca
Published: June 2021

The chapter studies the complex relationship between state and society, drawing on scholars including Timothy Mitchell and Joel Migdal who see the distinction between state and society as produced through practice. It looks at how Uganda’s ruling regime manipulates the relationship between state presence and absence, such that citizens are sometimes categorized as outside the state, sometimes as agents of the state, and—most often—placed in a liminal space where their standing vis-à-vis the state is ambiguous. The chapter examines Uganda’s flagship community policing programme, Crime Preventers, described as a ‘floating population’ that works as the regime’s ‘eyes and ears’ across the country. By mobilizing crime preventers, the regime fostered the possibility of state presence while keeping crime preventers themselves in a liminal space from which they could make few claims on state authorities.
Arbitrary Governance in Africa and Beyond
Authors: Tapscott Rebecca
Published: June 2021

The book concludes with a discussion of the theoretical and empirical implications of arbitrary governance today. It highlights the implications of the findings for literature on authoritarian regimes and state formation, and looks at the additional cases of Ethiopia, Rwanda, and Zimbabwe to further probe the external validity of the theory. The analysis shows that aspects of arbitrary governance are common across cases, and that institutionalized arbitrariness can usefully be applied beyond Uganda. The chapter concludes by discussing avenues for future research, including how international aid and improvements in surveillance technologies shape arbitrary governance, and the resultant dynamics between state and society in this type of modern authoritarian regime.
The Advent of a New Banking System in the US
Authors: Cunha João Rafael
Published: June 2021

The 1980s was one of the most eventful and consequential decades in the development of the US financial system. During this decade, the regulatory framework established in response to the Great Depression started to be dismantled. These regulatory changes were a key driving force behind the transformation of the banking sector. Moreover, the end of the decade saw the most serious banking crisis since the Great Depression. This pattern of deregulation and crises, which started in the 1980s, has continued until the present. Thus, it is worth study this period in greater detail and the consequences it has had for the US banking and financial system. The chapter argues that the deregulatory process that started in the 1980s in the banking industry in the United States has changed the profile of this sector. Between the Great Depression and the 1980s, the banking sector in the United States was a stable, yet not competitive sector. The financial deregulation of the 1980s changed this sector to a competitive, yet unstable one. This deregulatory process occurred mostly as a response to the economic conditions of the 1970s.
Fifty Years of Financial Regulation in Germany
Authors: Kaserer Christoph
Published: June 2021

This chapter gives an overview on how financial market regulation evolved in Germany since the 1970s. The picture presented is somehow contradicting, as it seems that banking regulation and capital market regulation evolved in a quite different way. As far as banking regulation is concerned, it will be shown that starting with the Herstatt crisis in 1974 there was a clear trend towards tightening and increasing the regulatory perimeter. By analysing how the budget of the German banking supervision authority evolved since 1988, this claim will also be corroborated empirically. The picture with respect to capital market regulation is quite different, however. Here, the regulatory process started back in the year 1990 and, at least for the first decade, it was focused towards liberalizing and modernizing the German capital market. It will be argued that there is an underlying public choice mechanism able to explain this different development in two adjacent areas of financial market regulation.
The Electrical Telegraph
Authors: Solymar Laszlo
Published: June 2021

Many attempts at realizing an electric telegraph are discussed starting in the 18th century. The crucial discovery that gave renewed impetus to the search was that of Oersted’s concerning the effect of electric current upon a magnetic needle. The first line in England was installed between Paddington and West Drayton. The contributions of various inventors like Gauss, Weber, Shilling, Cooke, and Wheatstone are discussed; also the effect on diplomacy, war and ordinary life, including women’s employment, is examined. Some famous telegrams, e.g. Ems, Kruger, Zimmerman, are put into their historical context, so is the telegraphic contact between Kerensky (Head of the Provisional Russian government at the time) and Kornilov, Commander of the Armed Forces.
The Telephone Revisited
Authors: Solymar Laszlo
Published: June 2021

The telephone becomes widespread in Europe (particularly in Denmark and Sweden) and in the US. In France, according to Colette, a popular authoress at the time: “The telephone is only for men concerned with important business matters and for women who have something to hide.” The principles of sound transmission and the operation of the telephone are discussed in simple terms. The use of the telephone is recommended in advertisements for contact with domestic staff and a cartoon is shown depicting the usefulness of the telephone by contacting the police in case of a burglary. The role of the telephone in revolutions, in civil wars, and during the German Occupation of France is discussed.
Microwaves
Authors: Solymar Laszlo
Published: June 2021

Various uses of the microwave spectrum are discussed. The first realisation was communications across the Channel by British and French engineers in 1931. During the Second World War enormous effort was expended to harness microwaves for radar. The research work was often done with limited resources (a poem by one of the participants describes the efforts). The operation of Microwave links described; how they can be used for Long Distance Communications. Satellite communications and the men who put them in practice (Rudi Kompfner and John Pierce of Bell Laboratories) are introduced and the first few satellites are described in somewhat more detail. Operation of microwave waveguides is explained.
Mobile Phones, Smartphones
Authors: Solymar Laszlo
Published: June 2021

The first mobile phone came out in the 1980s and cost almost $4,000 and weighed 2 pounds. In 1995 the penetration into the UK was only 7 per cent. Ten years later, practically all adults had mobile phones. The phenomenon is explained with the usual virtuous cycle theory but some other reasons are given too. Age distribution of mobile phone holders is plotted. The change from mobile phones to smartphones is presented and analysed. Some of the statistical hitches in the data are pointed out. The social effects of mobile devices, especially on children, are also discussed. Cartoons depicting how smartphones have been interfering with the habits of ordinary life are shown.
Legal Practitioners
Authors: Klose Fabian
Published: June 2021

In the wake of the efforts to fight the transatlantic slave trade during the nineteenth century the first system of international jurisdiction emerged, the so-called Mixed Commissions for the Abolition of the Slave Trade. These courts sought to guarantee the conviction of captured slave ships by a uniform set of practices, functions, and procedures for all of the commissions established throughout the Atlantic area. However, the Mixed Commissions were far from being a body of frictionless international cooperation. Instead, they were a fiercely contested place, where each member state sought to enforce its competing national interests concerning abolition. The aim of this chapter is to focus on this rather ambiguous character of the Mixed Commissions and its members. It focuses on the ambiguous roles of the commission members as legal actors, diplomats, and advocates in order to present the first system of international courts as a fiercely contested body of early international cooperation.
The ‘Lyric I’
Authors: Bugan Carmen
Published: June 2021

There are two aspects of personal identity that often clash in the artistic process originating in oppression; they destabilize the voice of the ‘lyric I’. This chapter raises several questions about the relationship between personal biography and the construction of a lyric speaker, and explores the notion of a poetics that insists on healing the damage that politics does to the family; it discusses what happens when private and public identities become conflated because of politics, and how poetry ‘acts’ on the sense of family as a social microcosm where the conflict between the sense of the political self and the private self takes place.
Resettling In The English Language
Authors: Bugan Carmen
Published: June 2021

When the native language becomes unstable, and writers are forced to abandon it, or when experience simply destroys the transaction of meaning or truth between a writer and her language, the notion of the ‘place of writing’ itself becomes destabilized and abstracted. This chapter probes the poet’s relationship with an adopted language, and offers a glimpse into the experience of writing in-between languages, hovering at the borders between them. As one re-settles in a new language, the native and the adopted languages play more complex and nuanced parts in the perception of self and of freedom, as the poet no longer defines one language in terms of another, one experience in terms of another, but seeks a language that brings feelings and experiences from both in a continuously evolving lyric.
Pornography, Subordination, and Silencing
Authors: Kramer Matthew H.
Published: June 2021

Whereas the first four chapters of this book have sought to articulate the content and implications of the principle of freedom of expression and have likewise sought to justify the sway of that principle as a moral absolute, the present chapter seeks to rebut some sophisticated arguments that have been propounded in recent decades by Rae Langton and other analytic feminist philosophers (including Ishani Maitra, Mary Kate McGowan, and Jennifer Hornsby) on the topic of pornography. With the aid of J.L. Austin’s speech-act philosophy, Langton has argued that the widespread availability of hard-core pornography in a society constitutes the subordination of women and causes the silencing of women. This chapter, the longest in the book, first refutes Langton’s claims about the constituting of women’s subordination and then contends that her claims about the causation of silencing—even if correct—are otiose as considerations in support of legal restrictions on pornography.
Countering Public Hate Speech
Authors: Lepoutre Maxime
Published: June 2021

This chapter considers how we should respond to deeply disrespectful or hateful public speech. Unless public hate speech is countered appropriately, it risks eroding the standing or dignity of its targets, and thereby preventing them from participating effectively in democratic public discourse. It is often held that this problem cannot adequately be addressed via ‘more speech’, and that, consequently, we must legally suppress hate speech. But this view relies on an overly limited understanding of how we might counter hate speech with more speech. First, it overlooks the role that the state can play in endowing ‘counterspeech’ with authority. Second, it overlooks the distinction between ‘negative’ counterspeech (which focuses on rejecting hateful perspectives) and ‘positive’ counterspeech (which instead affirms a countervailing and inconsistent perspective). Counterspeech that is both state-sponsored and positively framed constitutes a prima facie preferable tool than legal norms for upholding the standing of targets of hate speech.
The Problem of Goodwill
Authors: Lepoutre Maxime
Published: June 2021

This chapter considers the problem of goodwill. According to this concern, productive public discourse requires more goodwill—and, in particular, more trust—than typically obtains in divided societies. The chapter offers a two-pronged response to this worry. First, once we appreciate the systemic character of public discourse, it becomes apparent that productive public discourse demands far less goodwill than one might think. Second, even when levels of mutual dislike are too high for people productively to engage with one another, we can use public discourse to regenerate the missing goodwill. More specifically, features of public discourse that are widespread in non-ideal conditions—namely hypocrisy, anger, and even the occurrence of hate speech—have properties that can be harnessed to rebuild goodwill in divided societies. This might seem counter-intuitive: prima facie, these features of public speech seem wholly at odds with trust and goodwill. The present chapter, however, challenges this common intuition.
The Problem of Political Ignorance
Authors: Lepoutre Maxime
Published: June 2021

This chapter turns to the problem that political ignorance poses for democratic public discourse. It is often held (1) that ordinary citizens know too little to engage competently in public debates about politics and (2) that, because of the influence of group identity on political beliefs (or ‘group cognition’), this problematic ignorance is here to stay. The chapter argues that this influential worry fails, because it misunderstands the epistemic function of social group identities. The experiences involved in being a member of a particular social group are epistemically useful for deciding whose political judgment and what political information to trust. This is true even when it comes to scientific questions that bear on political issues, and even when people are dogmatically committed to their group perspectives. So, group cognition constitutes a useful tool for managing and overcoming political ignorance—and, by extension, for defusing the threat it raises for public discourse.
Resisting Political Minimalism
Authors: Lepoutre Maxime
Published: June 2021

In light of the challenges to inclusive public discourse discussed in Chapters 5 to 7, one might lose patience with this ideal. On this line of thought, we would do better, for the time being, to pursue a more minimalistic political ideal, which jettisons diverse and large-scale public discourse. The present chapter demonstrates that this is a mistake. Even if widespread political ignorance, together with the mutual ill will, dogmatism, and fragmentation that sustain it, are problematic for inclusive public discourse, they are just as problematic for the political models that are touted as alternatives. Accordingly, departing from the ideal of inclusive discourse because of these difficulties is misguided. Far from being the source of the problem, inclusive democratic speech is best understood as an attempted solution to these difficulties. The chapter concludes that, given that these difficulties are ubiquitous, and given the promise of speech-based innovations, we must try to make this solution work.
An Evaluative Framework
Authors: Lyman R. Lee
Published: June 2021

North American anthropologists and archaeologists have long confused the Midas-touch-like transformational evolution of Lewis Henry Morgan, Edward B. Tylor, and Herbert Spencer with the variational evolution of Charles Darwin. Following Franz Boas, evolution as a theory of change was allegedly discarded by North American anthropologists and archaeologists at the beginning of the twentieth century. However, they used the term “development” instead of “evolution” and spoke of culture change in evolutionary terms, often mixing elements of the theories and ontologies of transformational and variational evolution. Documenting culture change under variational evolution demands the materialist paradox be circumvented. This paradox highlights the question: How do we measure change in continuously variable phenomena? Paleontologists adopted the approach that each population of organisms is polymorphic; individuals are members of the same species but formally variable. Paleontologists compare central tendencies of temporally sequent populations, or chronospecies. Archaeologists who undertook frequency seriations adopted an approach that focuses on morphospecies, forms or types that occur in two or more temporally sequent populations. The occurrence of multiple types per temporal period highlights the variation upon which a sorting mechanism such as selection works, and the occurrence of one or more types in each of two or more temporally sequent assemblages provides evidence of connection between them required of studies of change. Recognizing that graph types, how phenomena are parsed into types, and theories of change are mutually influential allows evaluation of archaeological graphs of change in terms of their implied theories and ontologies.
Shopping Around and One-Off Graphs
Authors: Lyman R. Lee
Published: June 2021

Given explicit recognition between ~1915 and the 1930s that certain artifact types display unimodal frequency distributions over time, archaeologists initially presented tables of those frequencies but by the 1930s were experimenting with different types of graphs to present visual images of culture change. The lack of familiarity with graph theory and graph grammar meant numerous kinds of graph were published, often only once each as researchers sought effective (readily deciphered) and efficient (minimal ink and space) graph forms. These experimental graph types range from fairly simplistic to complex and virtually indecipherable. Lack of decipherability and errors in some graphs reflect poor understanding of the principles of graph construction and the precise nature of what a graph type is meant to illustrate. The analytical focus on culture history and recognition that artifact form varied along both time and geographic space led to some efforts to incorporate all three dimensions—form, time, space—into some graphs. It is not surprising that in the search for a useful graph type, the one-off graphs variously implied transformational, variational, and a combination of variational and transformational evolutionary change.
The Fourth (and Influential) Introduction of Spindle Graphs
Authors: Lyman R. Lee
Published: June 2021

Close examination of James A. Ford’s self-reported 1952 history of how he developed the centered and stacked bars style of spindle graph for which he is famous indicates he likely invented this kind of spindle graph with a bit of assistance from his colleagues George Quimby and Gordon Willey. In the 1930s, his diagrams of culture change were spatio-temporal rectangles or bar graphs; his first centered and stacked bars spindle diagram appeared in the 1949 published version of his doctoral dissertation. That graph style was picked up by American Southwest archaeologist Paul S(ydney) Martin that same year; Martin had, like many of his colleagues, initially used line graphs and bar graphs to illustrate culture change. Subsequently, numerous individuals adopted Ford’s centered and stacked bars form of spindle diagram. During the 1950s in Europe, French Paleolithic archaeologist François Bordes adopted ogive or cumulative relative frequency curves as a graphic means to compare assemblages of lithic tools. Quickly adopted by many European archaeologists, this graph type was only occasionally used in North America. After Ford, most graphs diagramed variational evolutionary change.
Final Thoughts
Authors: Lyman R. Lee
Published: June 2021

Graphs are analytical tools and communication tools, and they summarize visually what has been learned. Granting that a major purpose of archaeology is to document and explain culture change, it is odd that the hows and whys of graphing culture change have received minimal attention in the archaeology literature. Spindle graphs will likely continue to be the most frequently used graph type for diagraming change, but continued development of computer software may result in new graph types and styles. Recent modifications to spindle graphs include scaling bar thickness to temporal duration of the represented assemblage. Classic data on temporal change in kaolin pipe stem hole diameters can be graphed using a regression line, a bar graph, and a spindle graph; the different graphs highlight that how phenomena are classified, how data are graphed, and one’s theory of change are mutually influential. Deciding which graph type to use in any particular situation will depend on what the researcher hopes to illustrate, along with the goal to produce a readily deciphered graph. The majority of archaeological graphs that appeared in the twentieth century depict variational evolution. Once developed in the late 1940s, spindle graphs quickly became the graph type preferred by North American archaeologists. There is weak circumstantial evidence archaeologists may have borrowed the idea of spindle graphs from paleontology, but it seems more likely the idea was stumbled upon by early archaeologists who perceived unimodal pulses in artifact frequencies over time and developed general models of those pulses.
Authenticity, Self-Actualizing, and Self-Authorship
Authors: Bauer Jack
Published: June 2021

The transformative self aims toward authenticity and self-actualizing, which this chapter addresses from a developmental perspective. Two forms of authenticity are distinguished. Essentialist authenticity defines the true self as solely a matter of self-discovery and being true to one’s inborn traits or perceived soul. Existentialist authenticity also values self-discovery but emphasizes self-invention and being true to one’s values. Essentialist authenticity does not necessitate moral concerns, but existentialist authenticity does. The chapter argues that authenticity emerges not only via the matching principle of authenticity (matching actions with some true self) but also via the poiesis principle (the humane, self-making processes and perspectivity of a quiet ego). Youthful authenticity emphasizes independence and identity consolidation, whereas mature authenticity emphasizes interdependent self-actualizing. The chapter then examines self-actualization as maturely authentic self-understanding. Finally, the chapter reframes Maslow’s hierarchy of needs to correct common oversimplifications of belongingness and esteem in light of the developing, transformative self.
Gelatin-biofermentative unsulfated glycosaminoglycans semi-interpenetrating hydrogels via microbial-transglutaminase crosslinking enhance osteogenic potential of dental pulp stem cells
Authors: La Gatta Annalisa , Tirino Virginia , Cammarota Marcella , La Noce Marcella , Stellavato Antonietta , Pirozzi Anna Virginia Adriana , Portaccio Marianna , Diano Nadia , Laino Luigi , Papaccio Gianpaolo , Schiraldi Chiara
Published: June 2021

Gelatin hydrogels by microbial-transglutaminase crosslinking are being increasingly exploited for tissue engineering, and proved high potential in bone regeneration. This study aimed to evaluate, for the first time, the combination of enzymatically crosslinked gelatin with hyaluronan and the newly developed biotechnological chondroitin in enhancing osteogenic potential. Gelatin enzymatic crosslinking was carried out in the presence of hyaluronan or of a hyaluronan–chondroitin mixture, obtaining semi-interpenetrating gels. The latter proved lower swelling extent and improved stiffness compared to the gelatin matrix alone, whilst maintaining high stability. The heteropolysaccharides were retained for 30 days in the hydrogels, thus influencing cell response over this period. To evaluate the effect of hydrogel composition on bone regeneration, materials were seeded with human dental pulp stem cells and osteogenic differentiation was assessed. The expression of osteocalcin (OC) and osteopontin (OPN), both at gene and protein level, was evaluated at 7, 15 and 30 days of culture. Scanning electron microscopy (SEM) and two-photon microscope observations were performed to assess bone-like extracellular matrix (ECM) deposition and to observe the cell penetration depth. In the presence of the heteropolysaccharides, OC and OPN expression was upregulated and a higher degree of calcified matrix formation was observed. Combination with hyaluronan and chondroitin improved both the biophysical properties and the biological response of enzymatically crosslinked gelatin, fastening bone deposition.
Estate deadlock—when unanimity between executors is a pipe dream
Authors: Gardner Robert , Minns Sonia
Published: June 2021

This article looks at a recent judgment of the Royal Court of Jersey in which two of the five executors sought relief from the Court aimed at breaking the deadlock which had plagued the administration of the estate for much of its 19 years. The Court agreed to a request to delegate the final stages of the administration (which mainly related to selling some apartments in Malaysia) to the court appointed administrator. Whilst final sign off for any material steps rests with the executors themselves, a mechanism has been built into the orders which allows the Viscount of Jersey to sign documents on behalf of any recalcitrant executor, subject to that executor being able to apply to Court if he or she feels strongly enough to file an objection.
Trusts of the family home: it’s not just the judges who are confused
Authors: Atkins Scott
Published: June 2021

The decision of the Court of Appeal in the recent case of O’Neill v Holland was, on the one hand, a useful reminder that detrimental reliance is always part of the necessary ingredients to establish a constructive trust of the family home.

The Court of Appeal agreed that the District Judge, at trial, had misdirected herself on the issue of detrimental reliance and had not appeared to realise that it was a key attribute required to underpin a constructive trust. On the other hand, the approach taken by the Court of Appeal in its decision could itself be clearer and it is suggested that, when the surface of the decision is scratched away, the decision does little to clarify the principles in this area. Rather oddly, it might be an instance of where going back to first principles is not necessarily the best approach to take.
Myo1c, an unconventional motor that maintains glomerular filtration function
Authors: Arif Ehtesham , Mallik Leena , Rathore Yogendra S , Kumari Babita , Ostap Michael , Ashish FNU , Holzman Lawrence B , Nihalani Deepak
Published: June 2021

Podocytes and their specialized junctions “slit diaphragm” are key components of glomerular filtration system and their dysfunction is associated with impaired kidney function. We recently demonstrated that motor protein Myo1c mediates translocation of slit diaphragm proteins Neph1 and Nephrin from cytoplasm to podocytes cell membrane that is critical for renal function. In this study, we investigated physiological significance of Myo1c in maintaining glomerular filtration barrier using zebrafish as a model system. In addition, we performed structural and biochemical experiments to decipher the interacting regions in Myo1c and Neph1 that provides mechanistic insight into the assembly of Neph1 and its complexes at podocyte membrane. Knockdown of Myo1c in zebrafish using morpholinos impaired the glomerular filtration function. The solution structures of full length Myo1c in complex with the cytoplasmic domain of Neph1 was resolved using small/wide angle X‐ray scattering. The structural analysis revealed multiple regions in Myo1c and Neph1 that mediate this interaction. Binding mutants derived from this analysis confirmed the validity of this approach and the imaging experiments further demonstrated the inability of these mutants to localize at podocyte cell membrane and rescue a renal phenotype in zebrafish Neph1 knockdown model. Collectively, these results support a critical role for Myo1c in renal physiology.

Research support: Research support from NIH and NIDDK, Grant RO1 1R01DK087956 to D. N., DK080751 to L.B.H and NephCure foundation (NCF) for the NephCure Postdoctoral Grant, 2012‐RFP‐001 to E. A.
Chronic Exposure of Clonal Pancreatic β‐cells (INS‐1 832/13) to Pyruvate Inhibits Glucose‐induced Insulin Secretion
Authors: Burritt Nathan Edward , Corkey Barbara , Deeney Jude T.
Published: June 2021

Objective

Type 2 diabetes (T2D) occurs when pancreatic β‐cells fail to compensate for insulin resistance. Insulin resistance can be caused by a sustained elevation in insulin secretion, which may develop through a mechanism independent of the well‐established pathway described for fuel‐stimulated secretion. We hypothesize that nutrient availability can alter the redox state (NAD(P)H/NAD(P) ratio) leading to increases in reactive oxygen species (ROS) ultimately affecting insulin secretion.

Methods

To test this hypothesis we have incubated clonal pancreatic β‐cells (INS‐1 832/13) in increasing concentrations of Pyruvate (Pyr) (1–20 mM) or in varying ratios of Pyr and Lactate (Lac) for18–72 hrs in order to modify the REDOX capacity of the cell. Insulin secretion (HTRF), REDOX (autofluorescence), while insulin secretion and total insulin content where measured for Pyr and Lac.

Results

Pyr exposure decreased insulin secretion in a concentration dependent manner with a maximal inhibition of ~60% occurring at 5 mM.

Conclusion

Chronic exposure of INS‐1 cells to extracellular Pyr and Acoc inhibits insulin secretion by changing the REDOX state of the cells, affecting both insulin secretion and insulin content in a dose dependent manner.
Modulation of Bcl‐2 Proteins in an in Vitro Model of Sepsis
Authors: Crum Jo Anne , Del Gaizo Moore Victoria
Published: June 2021

Bcl‐2 family proteins regulate mitochondrial apoptosis and have been shown to be involved in a variety of diseases. In sepsis, systemic inflammatory response to pathogens, apoptosis is triggered in immune cells as a result of the cytokine storm induced by sepsis. Immune cell death is not the only damage caused by sepsis and the mechanism of cellular injury on end organs is unknown despite advances in modern medicine. Much of the mortality associated with sepsis is a result of end organ failure, particularly the kidneys. Research has shown that a small amount of apoptotic cell death is characteristic in acute renal injury associated with sepsis, thus Bcl‐2 family proteins should be involved in renal death as a result of septic shock. Use of a two‐step cell culture model stresses immune cells to stimulate cytokine release comparable to the cytokine storm found in sepsis, which can then be harvested and used to treat cultured kidney cells to induce death. Examination of Bcl‐2 proteins after treatment with stimulated cytokines showed a decrease in cell viability; an increase of BH3 only, pro‐apoptotic proteins; and a decrease in anti‐apoptotic Bcl‐2 confirming their hypothesized involvement. Results provide hope for elucidation of the mechanism of sepsis from which more efficient treatments can be developed. Research funded by Elon University URP, Department of Chemistry, Elon College Fellows, and the Provost Award to VDGM.
Design and Characterization of an EHD1 Inhibitor
Authors: Baleja James , Corlin Tiffany , Kamens Alissa , Alt‐Holland Addy , Kritzer Joshua
Published: June 2021

The EHD1 protein coordinates the expression of surface proteins, such as β1 integrins, that are highly expressed in our human squamous cell carcinoma (SCC) cell line. EHD1 mediates its effects via its Eps15‐homology (EH) domain that binds proteins containing an NPF sequence motif. This motif forms a β‐turn when bound to the EH domain. Since cyclization promotes turn formation, we asked to what extent constraining a linear NPF peptide promotes turn formation and high affinity. We designed a cyclized NPF peptide using a model of an EH domain‐NPF complex. Linear and cyclized peptides were synthesized, affinities were measured and NMR structures were determined. Head‐to‐tail cyclization increased binding affinity about 5‐fold (Kd, linear=4.7 μM vs. Kd, cyclic=1.0±0.2 μM). Although the linear peptide showed cis‐trans isomerization and poor chemical shift dispersion in NMR spectra, the cyclized peptide adopted a single conformation and higher chemical shift dispersion. Cyclization clearly improves the structure and binding affinities of peptide‐based inhibitors of EHD1 EH domains. We are currently testing whether cyclization improves stability and cell penetration, which would permit the use of EH domain ligands as a novel approach to reducing β1 integrin levels on SCC tumor cells and inhibit disease progression. Supported by a “Tufts Collaborates!” grant (A.A‐H. and J.D.B.) and DP2OD007303 (J.A.K.)
An In‐Vitro Model of T Cell Exit from the T Cell Zone Mediated by Sub‐Regional Co‐Existing CCL19 and CCL21 Fields in Lymph Nodes
Authors: NANDAGOPAL SARAVANAN ANDALUR , Lin Francis
Published: June 2021

Chemokines CCL19, CCL21 and their receptor CCR7 are known key mediators for T lymphocyte recruitment to lymph nodes (LNs) and navigation within LNs. The current model of T cell exit from LNs requires additional guiding signals. However, a critical mechanism is missing to facilitate T cell exit from the T cell zone (TCZ). Based on our previous experimental and modeling studies, we propose that LNs sub‐regional CCL19 and CCL21 fields mediate T cell exit from the TCZ through CCR7 signaling. In the present study, we analyzed CCL19 and CCL21 distribution profiles in different LNs sub‐regions of mouse LNs sections by immuno‐fluorescent staining and confocal microscopy, and our results conceptually support the hypothesized LNs sub‐regional CCL19 and CCL21 fields. Furthermore, we established an in‐vitro model to quantitatively examine the migration of activated human blood T cells in simulated LNs sub‐regional CCL19 and CCL21 fields followed by cell surface CCR7 expression analysis using a previously described microfluidic system. Our results suggest that CCL19 and CCL21 mediate T cells migration in LNs sub‐regions. In particular, the results suggest the sequential actions by specific co‐existing CCL19 and CCL21 fields in the TCZ periphery and in the region further beyond for mediating T cell exit from TCZ, which is correlated with altered surface CCR7 expression. This research was funded by NSERC, CFI and MHRC.
Differential oligomeric nature of mEos2 and mEos3.2 fluorescent proteins is consequential to diffusion and confinement of membrane probes
Authors: Edwald Elin , Veatch Sarah L.
Published: June 2021

Lipid‐mediated membrane heterogeneity, often referred to as lipid rafts, is proposed to be an important organizing principle in mammalian cells. Using super‐resolution fluorescence localization imaging we track the diffusion of a large panel of fluorescent membrane probes ranging in size, mode of membrane anchoring, and putative ‘raft’ or ‘non‐raft’ phase‐association. Our expressed probes include fluorescently‐tagged palmitoylated or non‐palmitoylated versions of transmembrane domains including linker of activated T‐cell and hemagglutinin, and fluorescent protein anchored by GPI, palmitate and myristoyl moieties, or a geranyl‐geranyl moiety. The recent advent of photoconvertible fluorescent protein mEos3.2, a “true monomeric” mutant of its mEos2 predecessor1, has enabled us to compare directly monomeric and oligomeric versions of the same probes. Our results indicate that in some cases rates of diffusion are more than two fold lower in the mEos2 probes when compared to their mEos3.2 counterparts. Many mEos2‐labeled probes also differ from mEos3.2‐labeled probes in their exponents of anomalous diffusion. We attribute changes in mobility to the proteins’ differential propensity to oligomerize, and find that larger probes differentiate themselves more than smaller ones with respect to phase‐mediated mobility differences. We are using the clustering effect of mEos2, therefore, as a tool to elucidate phase heterogeneity. Funding for this project was provided by NIH: SV R00GM087810 and a start up grant from the University of Michigan.
Arrestin dependent activation of ERK1/2 in response to follicle stimulating hormone
Authors: Chevalier Samantha , Cohen Brian
Published: June 2021

The human follicle stimulating hormone (hFSH) is a member of the glycoprotein hormone receptor family involved in regulating gametogenesis. When hFSH binds to its receptor it triggers the production of cAMP via adenylate cyclase and causes the activation of MAP kinases like p38 and ERK1/2. The goal of these experiments was to determine if MAP kinase activation was dependent on cAMP activation of protein kinase A. To characterize the role of PKA we used the inhibitor H89 and then investigated p38 and ERK1/2 activation in response to FSH. No effect was seen from H89 on p38 and ERK1/2 activation. In other labs, beta‐arrestin has been implicated as a potential activator of ERK1/2. To determine the role of beta‐arrestin in FSH induced MAP kinase activation we used short hairpin RNA (shRNA) to knockdown beta‐arrestin 1 and 2. When beta‐arrestin was knocked down ERK 1/2 activation was decreased and activation of p38 was unchanged. This suggests that there are two different activation pathways for p38 and p44/42. Understanding the mechanism of activation of the MAP kinases could lead to future advances in contraception or therapies for improvement of fertility.
Rac1b, A Variant Of Rac1 Interacts With Calmodulin
Authors: Khanna Neha , Xu Bing , Chelikani Prashen , Bhullar Rajinder Pal
Published: June 2021

Rac1b, a splice isoform of Rac1, is up‐regulated in malignant colorectal and breast cancer. It contains an additional 19 amino acid insertion close to the switch II domain, a region important for Rac1 interaction with regulators and effectors. This insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in intracellular predominance of GTP‐bound Rac1b. Previously, a 14 amino acid region essential for calmodulin (CaM) binding has been established in Rac1. A similar region exists in Rac1b. This led to our hypothesis that Rac1b interacts with CaM. Western Blot analysis showed that endogenous Rac1b interacts with CaM‐Sepharose, and that Rac1b binds to pure CaM, in a calcium dependent manner. Experiments using W7, a potent CaM antagonist, revealed that W7 does not play a role in GDP/GTP binding to Rac1b. However, the role of CaM in the activation and function of Rac1b still remains to be analyzed and is being pursued.
The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment
Authors: Weaver Jeremy D , Wang Huanchen , Shears Stephen B
Published: June 2021

Diphosphoinositol polyphosphates (PP‐InsPs) link nutrient status to the regulation of cellular growth and energy homeostasis; PPInsP turnover may impact bioenergetic diseases such as diabetes. Yet the relationship between PP‐InsP synthesis and cellular bioenergetic health remains unclear. We now characterize the ATP‐driven kinase activity of human PPIP5K2. The enzyme's equilibrium point favors 80–90% synthesis of 1‐InsP7 and InsP8. Although PPIP5K2 synthesized ATP “in reverse” in vitro, physiological conditions favored ATP consumption (PP‐InsP synthesis), with PPIP5K2 displaying substrate‐stimulated ATPase activity (2 and 1.2 ATP molecules per 1‐InsP7 and InsP8 synthetic cycle, respectively). PPIP5K2 kinase was also insensitive to physiological changes to either [AMP], [ATP]/[ADP] ratio, or to [ATP] itself (ATP Km = 20–40 μM). Contrary to consensus in the field, these kinetic properties of PPIP5Ks ensure that “high energy” PP‐InsPs synthesis is protected against changes in cellular bioenergetic status. This work was supported by the NIEHS.
Dairy foods intake and bone health
Authors: de França Natasha Aparecida Grande , Peters Barbara Santarosa Emo , de Souza Wysllenny Nascimento , Camargo Marilia Rodrigues , Lazaretti‐Castro Marise , Martini Ligia Araujo
Published: June 2021

The association between dairy intake and bone metabolism was evaluated. A cross‐sectional study with 89 postmenopausal women with osteoporosis, mean age 68.4 ± 8.7 years was performed. Dietary intake was obtained by a 3‐day food record, bone mineral density and body composition were measured, and biomarkers of bone metabolism were analyzed. The mean intake of dairy was 345.2 ± 193.6 g. The calcium and vitamin D intake was 854.7 ± 367.7 mg and 4.6 ± 2.3 mcg respectively. The concentration of parathyroid hormone (PTH) was 61.5 ± 28.9 pg/mL and serum 25‐hydroxyvitamin D (25(OH)D) was 24.6 ± 10.4 ng/mL. The loss of bone density was most notable in lumbar spine (T‐score −2.8 ± 1.0) than in femur neck (T‐score −1.8 ± 0.8). The BMI was 26.6 ± 3.9 kg/m2, with 36.1 ± 5.8% of body fat. There was no correlation between dairy and bone mass density, PTH, 25(OH)D, and body composition. When the sample was divided according to the percentiles of dairy intake, there were statistically significant differences only in dietary parameters. The group with higher dairy intake (more than 455 g/day) ingested more energy, calcium and vitamin D, compared to the other groups (p < 0.05). There was no relation between dairy intake and markers of bone metabolism. Allow vitamin D status was observed in these postmenopausal women with osteoporosis. Furthermore the association with dairy foods intake suggests a potential benefit of dietary recommendation. FAPESP.

Grant Funding Source: FAPESP
Estrogen deficiency worsened Ca balance via downregulation of epithelial Ca transport proteins in aged female rats
Authors: Wong Man Sau , Dong Xiaoli , Zhang Yan
Published: June 2021

Estrogen deficiency impairs intestinal and renal Ca (re)absorption in the aged female rats. However, it is unclear if estrogen and vitamin D endocrine system interact to alter Ca transport in aging animals. Eleven‐month‐old female sham or ovariectomized (OVX) rats were fed either a low‐Ca (LCD; 0.1% Ca, 0.65% P) diet or a high‐Ca (HCD; 1.2% Ca, 0.65% P) diet for 12 weeks. The interactive effects of estrogen deficiency and endogenous 1, 25(OH)2D3 on Ca balance, and the mRNA expression of Ca transport proteins in intestine and kidney were studied. The results showed that OVX rats fed with LCD resulted in negative Ca net balance. LCD suppressed serum Ca in OVX rats, but not in sham rats, resulting in the induction of serum PTH and serum 1,25(OH)2D3 levels. The surge in serum 1, 25(OH)2D3 levels in LCD‐fed OVX rats resulted in an increase in mRNA expression of intestinal transient receptor potential cation channel (TRPV6) and calbindin D9K as well as renal vitamin D receptor, but was unable to restore Ca balance in vivo. In contrast, the negative Ca balance was associated with the suppression of intestinal plasma membrane Ca pump (PMCA1b) and renal TRPV5, Calbindin D28K and PMCA1b mRNA expression in aged OVX rats. In conclusion, estrogen‐dependent and vitamin D‐independent downregulation of epithelial Ca transport protein expression might account for the negative Ca balance in aged female OVX rats. Funding sources: Niche Area Research Scheme (1‐BB8N) and Research Studentship from The Hong Kong Polytechnic University.
Physical activity and sedentary behavior in South Indian adults: Urbanicity, gender, and obesity
Authors: Chomitz Virginia Rall , Prabhu Sabarina Swarna , Thanikachalam Sadagopan , Vijayakumar Harivanza , Chui Kenneth Kwan Ho , Must Aviva , Bermudez Odilia , Thanikachalam Mohan
Published: June 2021

As obesity becomes more prevalent among South Asians, and populations become more urban, it is important to understand energy expenditure patterns and their relationship to obesity. A population‐based cross‐sectional survey in 8,042 (44% men (M), 56% female (F)) South Indian adults living in urban (n=2,199), semi‐urban (n=2,818) and rural (n=3,025) communities, used the WHO Global Physical Activity Questionnaire (GPAQ) and analysis guide (version 2) to collect and characterize respondent physical activity (PA) and daily sedentary hours (SH). Body Mass Index (BMI) 23–25 defined overweight and 25+ obese. General linear models were used to assess relationships. 27.2% M, 17.2% F respondents reported low, 65.5% M, 80.5% F moderate, and 7.3% M, 2.3% F high levels of PA with mean SH of 4.93 hours (SD 2.09) M, 4.90 (SD 1.88) F. Mean BMI was 24.72 (SD 4.55); BMI 23–25 19.0% M, 16.3% F; BMI 25+ 36.8% M, 54.6% F. SH patterns varied significantly by gender and urbanicity. Among M, SH increases linearly with increasing urbanicity, while F plateau at ~5 hours in both semi‐urban and urban. Mean BMI differed by urbanicity (p<.001) and gender (p<.001) with no interaction. Mean BMI is 1.91 times higher among F than M. Compared to urban residents, mean BMIs of semi‐urban and rural residents are 0.20 (p=.114) and 1.51 (p<.001) lower, respectively. As South Asians become more urban, the impact on energy expenditure and obesity must be assessed.