bluuebunny/crossref_metadata_2025 huggingface dataset:
Target Selection by Activists and the Structure of Competition
Authors: Abito Jose Miguel , Besanko David , Diermeier Daniel
Published: September 2019

This chapter extends the model to include two potential targets for campaigns. Activists targeting firms in different industries are shown to be likely to focus on the firm with the weaker reputation or greater sensitivity to reputation. The latter finding rationalizes the practice of secondary targeting in which an activist targets a consumer-facing company that cares a lot about its reputation rather than the companies in its supply chain creating the harm. In the case of two potential targes in the same industry, the competitive interdependence between the two firms affects the targeting decision. When it is weak—e.g., when firms sell differentiated products—the activist tends to target the firm whose characteristics predispose it to engage in more private regulation than its rival (e.g., the more patient firm, the market leader). When competitive interdependence is strong—as in commodities industries—the activist targets the firm predisposed toward less private regulation.
Future Climate and Potential Impacts at the Study Sites
Authors: van Oort Bob
Published: September 2019

The chapter opens with statements of uncertainties in climate modelling. Then, the most updated regional climate projections are downscaled by combining them with existing climate data on local level (statistical downscaling) and modified by local conditions (elevation, aspect). Climate scenarios are computed for 2030, 2050 and 2100 for all the six study sites (Chapters 4-9), using a 12 x 12 km grid.
Organic Farmers on the Ridge
Authors: Aase Tor H. , Chapagain Prem Sagar
Published: September 2019

Sermathang is a dynamic village that has banned all application of chemical inputs in farming. All organic materials are utilized as manure, including human ‘night soil’. Since Buddhists shall not kill living creatures, wild boars have become the main obstacle to increased productivity on their farms, especially after establishment of the neighbouring Langtang National Park. Quantity of precipitation is not going to change much in Sermathang, but a change from snow to rain will increase run-off and decrease recharging of local aquifers.
Stranded between ‘Good Floods’ and ‘Bad Floods’
Authors: Nischalke Sarah , Bisht Suman
Published: September 2019

Lawpani village in Assam is situated in a valley bottom and the present problem is too much water rather than scarcity. Villagers have adapted to normal floods that fertilize soils and make chemical fertilized unnecessary. But a recent major flood resulted in sand-casting of fields and death of livestock. The inhabitants are recent immigrants from Nepal and Bihar who lack the necessary resources to regain their former livelihoods, testifying to the importance of social capital in terms of resilience. The fact that native Assamese never settled on the plain is an index of recurrent damaging floods in the past.
Leisure, Surveillance, and the Private Sector in India
Authors: Thomas Pradip Ninan
Published: September 2019

This chapter furthers the exploration of surveillance in India against the background of the Snowden revelations and WikiLeaks by focusing specifically on the role played by the private sector in the extension of surveillance, often through public–private partnerships. It explores the political economy of the surveillance industries in India against the power of ‘code’ and ‘algorithmic power’. It highlights the role played by transnational search and social networks such as Google and Facebook, and the nature of the power to control affective behaviour. It also deals with the use of code in India’s leisure industries and illustrates Polanyi’s ‘double movement’ in the use of code by communities in India as an expression of its democratization.
Digital (Transgenic) Seed and Its Copy
Authors: Thomas Pradip Ninan
Published: September 2019

The politics of digital seed in India is one of the best illustrations of the fact that it is inherently difficult to contain any product that has been digitally processed. This chapter explores digital seed in India within the attempt to privatize seeds by companies such as Monsanto. Both seed and the turn towards precision agriculture can be seen as attempts to control the independence and sovereignty of farmers in India and curb their autonomy. This chapter deals with digital seed in the context of the farming crisis in India and highlights the spread of ‘copy seed’ and the virtual impossibility of curbing its use. Farmers are an extremely important vote bank and no government can risk alienating this sector. This chapter provides a succinct introduction to the global political economy of seed and precision agriculture and its rollout in India.
The Politics and Geopolitics of Internet Governance
Authors: Thomas Pradip Ninan
Published: September 2019

Internet governance (IG) became a global issue after the Snowden revelations that highlighted the fact that there was mass spying by privately owned companies on behalf of the NSA. This chapter deals with the politics of IG, the ambivalent nature of India’s shifting commitments to the multistakeholder model, and the role played by civil society in Internet politics in India against the background of ICANN’s own history and contemporary status. The Indian government’s position on IG is complex given that it has adopted both a statist attitude towards its governance and considered the ITU as a natural governor of the Internet, along with a position that is supportive of multistakeholderism, although this ethic is not reflected in its facilitation of civil society involvements at a local level.
Turbulent Times
Authors: Khandkar Arundhati C. , Khandkar Ashok C.
Published: September 2019

As the East India Company’s trade expanded, so did their control, influence, and interference in Indian politics, society, and local laws. The Meerut Mutiny of 1857 was the turning point for Indians to earnestly begin clamouring for freedom. To achieve that, however, bringing Indians together was a paramount task. So, the social reformers systematically began asking Indians to set aside caste-based discrimination practices and unite together against the Raj. Laxmanshastri espoused a reasoned and rational dialog as the principal way to bring people with opposing views together. He drew on the historiography of the dharma-shastras, pointing to the wide-ranging and rich polemical debates in the literature that allowed diametrically opposite views and interpretation. He believed in the central Upanishadic idea that all humans are Brahman. It was from that principle that he kept the injustices against Untouchables squarely in his vision, never losing sight of the idea of making India more equitable for all her citizens. While his command of the shastras was never questioned, changing deeply held biases proved to be more challenging, but he did succeed in getting the more orthodox upper caste members of Indian society to consider his arguments and pay more attention to the plight of the Untouchables.
A Relentless Search for Truth
Authors: Khandkar Arundhati C. , Khandkar Ashok C.
Published: September 2019

Laxmanshastri practiced what he preached. For him and in his household, Untouchables were treated no differently than brahmins. Although the domestic staff essentially came from the Untouchable community, he and his wife, Satyavati, were sure to encourage their children to study and get formal college education. Throughout his life, he used his scholarship to focus on the heterodoxy of thought within Hinduism, and the wide spectrum of religious beliefs and practices within the Hindu fold. For him, that was the truth and with that, he set personal examples of not adhering to any dogma blindly, of not discriminating against any individual on the basis of his or her hereditary caste. As an ardent humanist, he presented evidence, providing innovative arguments in simple terms, and with courage, encouraged respectful dialog in a bid to transcend convention instead of bowing to it. Like Tagore, he was in every respect one of India’s renaissance men. His writings and thoughts had an enduring quality. He became one of the leading voices in the evolution of a free, secular, modern, and progressive India.
Military Labour, Animals, and the Material Production of War
Authors: Nath Pratyay
Published: September 2019

This chapter explores the world of Mughal military logistics. It focuses on military labour, mobilization of animals, supply of resources, production of infrastructure, and transmission of intelligence. Shifting the focus from combat to logistics, this chapter makes three main points. First, it underlines the crucial role that the careful management of these logistical activities played in the overall military success of the Mughals. Second, it shows that much of these activities, in turn, were executed by an enormous logistical workforce, comprising a large section of the non-elite, non-combatant population of South Asia. It argues that the contribution of this non-elite workforce was no less important than the military aristocracy in creating the empire. Finally, it highlights that appreciating the complexity and importance of military logistics allows us to understand that war did not signify mere moments of rupture in Mughal history; rather, it characterized the quotidian life of the empire.
Ideology, Empire, and the Cultural Climate of War
Authors: Nath Pratyay
Published: September 2019

This chapter investigates the cultural climate of conquest at the Mughal court. It begins by discussing how the Mughals conceptualized the nature and meanings of kingship. It then goes on to probe the location of war and conquest within this ruling ideology. It argues that inspired by Nasirean akhlāq, the Mughals conceptualized the sovereign as a divinely-mandated instrument for establishing equilibrium, order, and—above all—justice across the world. They looked upon war as an unavoidable means of achieving this. This conceptualization of war in terms of the vague concept of justice allowed the empire a great degree of flexibility in terms of applying and legitimizing military violence. By studying different imperial narratives of war from the period under study, the chapter argues that this flexibility in turn fed a particular approach to war, whereby the empire expanded more by defeating and co-opting its adversaries than by eliminating them completely.
Introduction
Authors: Govindaraj V.C.
Published: September 2019

This introductory chapter begins with an overview of the raison d’etre for the existence of this particular branch of law—conflict of laws or private international law. It then discusses the appropriateness of the title ‘conflict of laws’, ways and means of avoiding conflicts, unification of international law, unification of rules of choice of law, the evolution of conflict of laws in retrospect and in prospect, modern theories of conflict of laws, the doctrine of comity, the doctrine of public policy, and the theory of vested or acquired rights.
Law of Persons
Authors: Govindaraj V.C.
Published: September 2019

This chapter deals with the law relating to marriage and divorce, as interpreted and applied by courts in India. Marriage involves many topics/processes such as celebration, divorce, nullity, etc., and each one is accorded a different treatment by the concerned law. The following topics/processes under each matrimonial law are discussed: pre-solemnization requisites; solemnization; divorce; marriages solemnized under the Foreign Marriages Act, 1969; the conversion of spouses of the Hindu, Christian, and Parsi marriages to Islam, and right to polygamy after such conversion; conversion of Muslim women from Islam after dissolution of marriage under Muslim Law; and rights of a Muslim woman to seek divorce and maintenance.
Law of Persons
Authors: Govindaraj V.C.
Published: September 2019

This chapter discusses the law relating to children as interpreted and applied by Indian courts. It covers the following: custodial orders of minors as part of matrimonial reliefs; custodial orders of minors independent of matrimonial reliefs; the role of courts as parens patriae; foreign custody and guardianship order; law relating to property of children; declaration of legitimacy or parentage; proof of legitimacy; jurisdictional competence of Indian courts to grant declarations of legitimation; adoption; maintenance orders; and reciprocal enforcement of maintenance orders.
Validity of Marriage
Authors: Govindaraj V.C.
Published: September 2019

This chapter examines the inflexible and conservative attitude and approach of the courts in general, that has inexorably led them to treat marriage and its validity as omnific vis-à-vis correlative issues such as adoption, legitimacy, and rights of succession, testate or intestate, of a surviving spouse and children born of such marriage. It presents five cases highlighting the switch that had recently taken place in the judicial thinking that establishes the proposition that marriage cannot be treated as an all-purpose concept in respect of related issues such as adoption, legitimacy, and rights of succession of the surviving spouse and children born of a putative marriage. The chapter then discusses the validity of marriage under Section 283 of the Restatement (Second) of Conflict of Laws, 1971; the insulated approach of courts in England; and the hidebound attitude of Indian courts to marriage and other personal law issues.
Introduction
Authors: Eckle Hans-Peter
Published: September 2019

This chapter provides general introductory information on the book as whole, offering the reader an overview of and orientation within the book. It is deliberately short to avoid redundancies, and it briefly outlines the book’s six parts. The book’s focus is on selected concepts, methods, and mathematical techniques in the area of strongly interacting quantum matter systems, especially the various Bethe ansatz techniques, and also aims to provide guidance for the understanding of other strongly interacting systems.
The Anisotropic Heisenberg Quantum Spin Chain
Authors: Eckle Hans-Peter
Published: September 2019

This chapter introduces the Heisenberg model, a fully quantum mechanical model that describes the magnetism of localized magnetic moments. The one-dimensional version of the Heisenberg model, the Heisenberg quantum spin chain, provides a good picture of magnetic materials that belong to a class of insulating magnetic materials where the interaction of the magnetic moments in one particular direction is much larger than in the perpendicular directions, and which can be described with high accuracy as quasi- one-dimensional magnets. A detailed description of the Heisenberg quantum spin chain is followed by a discussion of its various special cases, in particular the special case of the anisotropic Heisenberg quantum spin chain, the so-called XXZ quantum spin chain. It considers the solution of eigenvalue problem of this quantum spin and leads to Bethe’s conjecture for the wave function.
Mathematical Tools
Authors: Eckle Hans-Peter
Published: September 2019

Chapter 19 introduces the mathematical techniques required to extract analytic infor- mation from the Bethe ansatz equations for a Heisenberg quantum spin chain of finite length. It discusses how the Bernoulli numbers are needed as a prerequisite for the Euler– Maclaurin summation formula, which allows to transform finite sums into integrals plus, in a systematic way, corrections taking into account the finite size of the system. Applying this mathematical technique to the Bethe ansatz equations results in linear integral equations of the Wiener–Hopf type for the solution of which an elaborate mathematical technique exists, the Wiener–Hopf technique.
Megachurch: The Drug That Works
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

Megachurches are growing in size and number in the United States with no indication of slowing down. We argue that their success is due to motivating their congregations with emotional energy that stimulates intense loyalty and a desire to come back repeatedly to get recharged. Megachurches are like drug dealers offering members and nonmembers alike their next hit of emotional energy. Ritual life is critical for the generation of emotional energy, but so are the minimally counterintuitive ideas that capture attention, channel the emotional energy, and rally loyalty and motivation to keep coming back for more. However, these ideas are not sufficient on their own but need to be charged with emotional energy from rituals to inspire loyalty from participants.
The Problem of Cooperation and Homo Duplex
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

Humans are homo duplex—they are both individual and social—and they struggle with the coexistence and/or integration of these two sides to their human nature. Given this, what encourages cooperation among strangers? Our claim is that religion is the most effective method of facilitating human cooperation and that megachurches are particularly successful at doing so. Megachurches provide attendees with rituals and opportunities to discipline and increase self-control, selfless behavior, and cooperation. At the same time, they focus on the other side of homo duplex—the need to exert the ego—which is evident in how they lift the individual and nurture each person’s gifts and talents.
Defining Religion: Sacred Moral Communities
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

We provide and support our definition of religion. Religion is (1) a social enactment of a desire for the ultimate. It is (2) embodied in ritual practices; (3) described by systems of symbols and beliefs; (4) developed in communal settings, and often institutionally legitimated. (5) Religion interacts and negotiates with powers and forces that are experienced as within and beyond the self and group. (6) This power or force is most often referred to as god/spirit or gods/spirits. (7) The affective experience of ritual, and the symbolic and social boundaries constructed in rites, mobilize group identity and bind the group into a moral community. Last, (8) these moral communities produce networks of solidarity, and carry the potential for tension and, more rarely, conflict and violence within and between groups.
Desire to Re-member
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

In this chapter, we show how megachurches satisfy attendees’ desire to belong in a community of like-minded others. We describe the process by which attendees go from being spectators to being active members, and the key role that small groups play in this process. Small groups connect attendees to others, allow them to feel accepted, make a large church feel small, and provide them with emotional energy in between weekend services. Megachurches offer a wide variety of small group options in an effort to meet their attendees’ every need, which include small groups focusing on marriage that become a critical factor in creating what we call megachurch marriage culture.
Conclusion: Havens of Health or Habitats for the Prosperity Gospel?
Authors: Wellman James K. , Corcoran Katie E. , Stockly Kate J.
Published: September 2019

The dominant assessment of megachurches, in both popular culture and scholarship, is that they tend to be havens of commerce and exploitation, and purveyors of the prosperity gospel. After sifting through the data on members in twelve representative American megachurches, looking at people who were longtime members and leaders, those who were new members, and those that were just visiting, we found something quite different. We found wells of goodness, satisfaction, generosity, and inspiration. We found religious organizations that have a certain genius for meeting the needs of what Durkheim called homo duplex. Megachurches are organizations that meet the desire of humans to flourish as individuals and to do it in a group—an equipoise that is rare but deeply satisfying.
The Border
Authors: Schain Martin A.
Published: September 2019

This book is a comparative study of how and why border policy has become increasingly important, politicized, and divisive in Europe and the United States. It focuses on how border governance has emerged as an important focus of policy in itself, rather than merely contingent on trade and, above all, on immigration policy. New data indicate a massive increase of walls and barriers between countries after 2001. In our more globalized world, borders are back with a vengeance. However, at the same time that more controls have been established, the flow of people and the growth of trade have continued at an impressive rate. The claims by scholars and political actors of an emerging Fortress Europe and Fortress America have clearly been exaggerated. They express goals and intentions, rather than outcomes. The argument in this book is that the gap between objectives and outcomes should be understood as a result of the complex politics of the border and border control. Although there has been consistent support for harsher border control on both sides of the Atlantic, there has also been important, if more focused, support for more open borders and more permissive border control. If electoral politics often favor border restriction, the politics of policymaking can be more advantageous for groups that favor access. These are separate political tracks, the author maintains, but they are always in dynamic interaction.
Start with the Problem: Establishing Research Relevance with Integrative Public Administration
Authors: Carboni Julia L , Dickey Todd , Moulton Stephanie , O’keefe Sean , O’leary Rosemary , Piotrowski Suzanne J , Sandfort Jodi
Published: September 2019

A key question of each Minnowbrook has been how public administration scholarship can be relevant to practice (Carboni and Nabatchi 2019; Nabatchi and Carboni 2019; O’Leary, Van Slyke, and Kim 2010). This question remains salient today, as public administration scholarship is increasingly distant from the challenges identified by practitioners. Academic research agendas are often disconnected from the social issues and challenges of public governance. Field norms incentivize and exacerbate this cleavage. As a result, past calls for more practice-oriented scholarship lack widespread implementation. In this essay, we propose modest shifts in how academic research is conducted to link it with problems, issues, and opportunities identified by the public service practitioners and professional communities. We refer to this shift as Integrative Public Administration. We also identify and make suggestions about how to change some field level conditions that hamper the shift to Integrative Public Administration.
Diversification Through Trade*
Authors: Caselli Francesco , Koren Miklós , Lisicky Milan , Tenreyro Silvana
Published: September 2019

A widely held view is that openness to international trade leads to higher income volatility, as trade increases specialization and hence exposure to sector-specific shocks. Contrary to this common wisdom, we argue that when country-wide shocks are important, openness to international trade can lower income volatility by reducing exposure to domestic shocks and allowing countries to diversify the sources of demand and supply across countries. Using a quantitative model of trade, we assess the importance of the two mechanisms (sectoral specialization and cross-country diversification) and show that in recent decades international trade has reduced economic volatility for most countries.
Nutritive value of enzyme-supplemented carinata meal for growing pigs1
Authors: Hong Jinsu , Lee Jung Wook , Pettersson Dan , Woyengo Tofuko A
Published: September 2019

Carinata meal is increasingly available for livestock feeding. However, the effects of supplemental phytase and fiber degrading enzymes on nutritive value of carinata meal for pigs have not been reported. Objective of the study was to evaluate the standardized ileal digestibility (SID) of amino acid (AA), and digestible energy (DE) and net energy (NE) values of phytase- and fiber-degrading enzymes-supplemented carinata meal for growing pigs. Ten ileal-cannulated pigs (initial body weight = 53.9 ± 4.76 kg) were fed 4 diets in a replicated 4 × 4 Latin square design with two additional columns to give 10 replicates per diet. Diets included a corn-soybean meal (SBM)-based basal diet, basal diet with 25% carinata meal, basal diet with 25% carinata meal plus phytase at 2,000 FTU/kg and multi-carbohydrase at 0.2 g/kg, and in addition a nitrogen-free diet. The multicarbohydrase supplied 4 units of xylanase, 10 units of β-glucanase, and 1,000 units of pectinase per kilogram of diet. The ratio of corn to SBM and soybean oil in carinata meal-containing diets was identical to that in the corn-SBM-based basal diet to allow calculation of AA and energy digestibility of carinata meal by the difference method. On a dry matter basis, carinata meal contained 50.2% crude protein, 0.88% ether extract, 15.37% acid detergent fiber, 1.82% Lys, 0.96% Met, 1.89% Thr, and 0.64% Trp, respectively. The SID of Lys, Met, Thr, and Trp for carinata meal were 51.4%, 82.2%, 65.9%, and 85.9%, respectively. The DE and NE values for carinata meal were 3,427 and 1,828 kcal/kg of dry matter, respectively. Supplementation of a combination of phytase and multicarbohydrase did not affect the apparent ileal digestibility of AA and SID of AA for the corn-SBM-carinata meal-based diet, and for the carinata meal. However, the combination of phytase and multicarbohydrase did improve (P < 0.05) apparent total tract digestibility, and DE and NE values for carinata meal by 9.4%, 9.5%, and 12.4%, respectively. In conclusion, the enzymes used in the current study could be added in carinata meal-based diets for growing pigs to improve the energy value.
Relationship Between Pregnancy-Associated Malaria and Adverse Pregnancy Outcomes: a Systematic Review and Meta-Analysis
Authors: Thompson Julie M , Eick Stephanie M , Dailey Cody , Dale Ariella P , Mehta Mansi , Nair Anjali , Cordero José F , Welton Michael
Published: September 2019

Background

Pregnancy-associated malaria (PAM) has been associated with adverse pregnancy outcomes like preterm birth (PTB) and low birthweight (LBW), which are among the leading causes of infant mortality globally. Rates of PTB and LBW are high in countries with a high burden of malaria. PAM may be a contributing factor to PTB and LBW, but is not well understood.

Methods

We conducted a systematic review and meta-analysis of studies examining the relationship between PAM and PTB or LBW using PubMed. The title and abstract of all studies were screened by two reviewers, and the full text of selected studies was reviewed to ensure they met inclusion criteria. Information regarding study characteristics and of PTB and LBW births among women with and without PAM was abstracted for included studies.

Results

Our search terms yielded 2237 articles, of which 18 met our final inclusion criteria. Eight studies examined associations between PAM and PTB, and 10 examined associations between PAM and LBW (population size ranging from 35 to 9956 women). The overall risk of LBW was 63% higher among women with PAM compared with women without PAM (95% CI = 1.48–1.80) and the risk of PTB was 23% higher among women with PAM compared with women without PAM (95% CI = 1.07–1.41).

Conclusions

These results indicate that infection with PAM is associated with PTB and LBW. Further understanding of the pathogenesis of disease and the immunologic changes that occur during pregnancy is essential for reducing the disproportional effects this disease has on this vulnerable population.
mTORC1 as a cell‐intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes
Authors: Raybuck Ariel L. , Lee Keunwook , Cho Sung Hoon , Li Jingxin , Thomas James W. , Boothby Mark R.
Published: September 2019

Ample evidence indicates that nutrient concentrations in extracellular milieux affect signaling mediated by environmental sensor proteins. For instance, the mechanistic target of rapamycin (mTOR) is reduced during protein malnutrition and is known to be modulated by concentrations of several amino acids when in a multiprotein signaling complex that contains regulatory‐associated protein of mTOR. We hypothesized that a partial decrease in mTOR complex 1 (mTORC1) activity intrinsic to B‐lineage cells would perturb lymphocyte development or function, or both. We show that a cell‐intrinsic decrease in mTORC1 activity impacted developmental progression, antigen receptor repertoire, and function along the B lineage. Thus, preimmune repertoires of B‐lineage cells were altered in the marrow and periphery in a genetic model of regulatory‐associated protein of mTOR haploinsufficiency. An additional role for mTORC1 was revealed when a B‐cell antigen receptor transgene was found to circumvent the abnormal B‐cell development: haploinsufficient B cells were profoundly impaired in responses to antigen in vivo. Collectively, our findings indicate that mTORC1 serves as a rheostat that shapes differentiation along the B lineage, the preimmune repertoire, and antigen‐driven selection of mature B cells. The findings also reveal a range in the impact of this nutrient sensor on activity‐response relationships for distinct endpoints.—Raybuck, A. L., Lee, K., Cho, S. H., Li, J., Thomas, J. W., Boothby, M. R. mTORC1 as a cell‐intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes. FASEB J. 33, 13202–13215 (2019). www.fasebj.org
LNX1 contributes to tumor growth by down‐regulating p53 stability
Authors: Park Rackhyun , Kim Hyunju , Jang Minsu , Jo Daum , Park Yea‐In , Namkoong Sim , Lee Jin I. , Jang Ik‐Soon , Park Junsoo
Published: September 2019

The well‐known tumor suppressor p53 inhibits the formation of various cancers by inducing cell cycle arrest and apoptosis. Although p53 mutations are commonly found in many cancers, p53 is functionally inactivated in tumor cells that retain wild‐type p53. Here, we show that the ligand of numb protein X1 (LNX1) inhibited p53‐dependent transcription by decreasing the half‐life of p53. We generated LNX1 knockout (KO) cells in p53 wild‐type cancer cells (A549, HCT116, and MCF7) using the clustered regularly interspaced short palindromic repeats (CRISPR)‐CRISPR‐associated protein 9 gene‐editing system. LNX1 KO activated p53‐dependent transcription by increasing the stability of p53. Moreover, lentivirus‐mediated overexpression of LNX1 decreased p53 protein levels and inhibited p53‐dependent transcription. LNX1 interacted with p53 and mouse double minute 2 (MDM2) and increased the ubiquitination of p53 in an MDM2‐dependent manner. Finally, we demonstrated that LNX1 was required for efficient tumor growth both in cell culture and in a mouse tumor xenograft model. These results collectively indicated that LNX1 contributed to tumor growth by inhibiting p53‐dependent signaling in p53 wild‐type cancer cells.—Park, R., Kim, H., Jang M., Jo, D., Park, Y.‐I., Namkoong S., Lee, J. I., Jang I.‐S., Park, J. LNX1contributes to tumor growth by down‐regulating p53 stability. FASEB J. 33, 13216–13227 (2019). www.fasebj.org
The cleaner shrimpLysmata amboinensisadjusts its behaviour towards predatory versus non-predatory clients
Authors: Caves Eleanor M. , Chen Catherine , Johnsen Sönke
Published: September 2019

In cleaning mutualisms, small cleaner organisms remove ectoparasites and dead skin from larger clients. Because cheating by predatory clients can result in cleaner death, cleaners should assess the potential risk of interacting with a given client and adjust their behaviour accordingly. Cleaner shrimp are small marine crustaceans that interact with numerous client fish species, many of which are potential predators. We usein situobservations of cleaner–client interactions to show that the cleaner shrimpLysmata amboinensisadjusts several behaviours when interacting with predatory versus non-predatory clients. Predatory clients were cleaned in a significantly lower proportion of interactions than non-predatory clients, and cleaners also exhibited a leg rocking behaviour—potentially signalling their identity or intent to clean—almost exclusively toward predatory clients. Incidence of leg rocking was positively correlated with client size, and laboratory experiments showed that it can be elicited by dark visual stimuli and decreases in illumination level. Thus, cleaners clean less frequently when predation risk is higher, and may use leg rocking as a signal advertising cleaning services and directed specifically at predators.
Weak radiofrequency fields affect the insect circadian clock
Authors: Bartos Premysl , Netusil Radek , Slaby Pavel , Dolezel David , Ritz Thorsten , Vacha Martin
Published: September 2019

It is known that the circadian clock in
Drosophila
can be sensitive to static magnetic fields (MFs). Man-made radiofrequency (RF) electromagnetic fields have been shown to have effects on animal orientation responses at remarkably weak intensities in the nanotesla range. Here, we tested if weak broadband RF fields also affect the circadian rhythm of the German cockroach (
Blatella germanica
). We observed that static MFs slow down the cockroach clock rhythm under dim UV light, consistent with results on the
Drosophila
circadian clock. Remarkably, 300 times weaker RF fields likewise slowed down the cockroach clock in a near-zero static magnetic field. This demonstrates that the internal clock of organisms can be sensitive to weak RF fields, consequently opening the possibility of an influence of man-made RF fields on many clock-dependent events in living systems.
Constraints on somite formation in developing embryos
Authors: Juul Jonas S. , Jensen Mogens H. , Krishna Sandeep
Published: September 2019

Segment formation in vertebrate embryos is a stunning example of biological self-organization. Here, we present an idealized framework, in which we treat the presomitic mesoderm (PSM) as a one-dimensional line of oscillators. We use the framework to derive constraints that connect the size of somites, and the timing of their formation, to the growth of the PSM and the gradient of the somitogenesis clock period across the PSM. Our analysis recapitulates the observations made recently inex vivocultures of mouse PSM cells, and makes predictions for how perturbations, such as increased Wnt levels, would alter somite widths. Finally, our analysis makes testable predictions for the shape of the phase profile and somite widths at different stages of PSM growth. In particular, we show that the phase profile is robustly concave when the PSM length is steady and slightly convex in an important special case when it is decreasing exponentially. In both cases, the phase profile scales with the PSM length; in the latter case, it scales dynamically. This has important consequences for the velocity of the waves that traverse the PSM and trigger somite formation, as well as the effect of errors in phase measurement on somite widths.
Cellular functions and molecular mechanisms of non-lysine ubiquitination
Authors: McClellan Amie J. , Laugesen Sophie Heiden , Ellgaard Lars
Published: September 2019

Protein ubiquitination is of great cellular importance through its central role in processes such as degradation, DNA repair, endocytosis and inflammation. Canonical ubiquitination takes place on lysine residues, but in the past 15 years non-lysine ubiquitination on serine, threonine and cysteine has been firmly established. With the emerging importance of non-lysine ubiquitination, it is crucial to identify the responsible molecular machinery and understand the mechanistic basis for non-lysine ubiquitination. Here, we first provide an overview of the literature that has documented non-lysine ubiquitination. Informed by these examples, we then discuss the molecular mechanisms and cellular implications of non-lysine ubiquitination, and conclude by outlining open questions and future perspectives in the field.
Eye pupil signals information gain
Authors: Zénon Alexandre
Published: September 2019

In conditions of constant illumination, the eye pupil diameter indexes the modulation of arousal state and responds to a large breadth of cognitive processes, including mental effort, attention, surprise, decision processes, decision biases, value beliefs, uncertainty, volatility, exploitation/exploration trade-off, or learning rate. Here, I propose an information theoretic framework that has the potential to explain the ensemble of these findings as reflecting pupillary response to information processing. In short, updates of the brain’s internal model, quantified formally as the Kullback–Leibler (KL) divergence between prior and posterior beliefs, would be the common denominator to all these instances of pupillary dilation to cognition. I show that stimulus presentation leads to pupillary response that is proportional to the amount of information the stimulus carries about itself and to the quantity of information it provides about other task variables. In the context of decision making, pupil dilation in relation to uncertainty is explained by the wandering of the evidence accumulation process, leading to large summed KL divergences. Finally, pupillary response to mental effort and variations in tonic pupil size are also formalized in terms of information theory. On the basis of this framework, I compare pupillary data from past studies to simple information-theoretic simulations of task designs and show good correspondance with data across studies. The present framework has the potential to unify the large set of results reported on pupillary dilation to cognition and to provide a theory to guide future research.
Physical activity and risk of breast and endometrial cancers: a Mendelian randomization study
Authors: Baurecht Hansjörg , Leitzmann Michael , O’Mara Tracy , Thompson Deborah J ,   the collaborators of the Endometrial Cancer Association Consortium, Teumer Alexander , Baumeister Sebastian E.
Published: September 2019

Abstract

Importance

The causality of the association between physical activity and risk of breast and endometrial cancers is uncertain because available evidence is based exclusively on observational studies, which are potentially susceptible to confounding and reverse causation.

Objective

To investigate whether increased physical activity is causally associated with decreased risk of breast and endometrial cancers, using a two-sample Mendelian randomization study design.

Design, Setting, and Participants

Genome-wide association studies of physical activity, breast cancer, and endometrial cancer, published up to April 31, 2019, were identified using PubMed and the GWAS catalog. Twelve single nucleotide polymorphisms (SNP) known at P < 5 × 10−8 to be associated with accelerometer-assessed or self-reported physical activity served as instrumental variables. Genetic summary data from four large consortia provided SNP-outcome associations [Breast Cancer Association Consortium; Discovery, Biology and Risk of Inherited Variants in Breast Cancer Consortium; Endometrial Cancer Association Consortium].

Main Outcomes and Measures

The primary outcomes were risk of breast cancer and risk of endometrial cancer. Secondary outcomes were estrogen receptor positive (ER+) and ER-breast cancers. Odds ratios (ORs) and 95% confidence intervals (CIs) per mean acceleration in milli-gravities of accelerometer-assessed physical activity and per one standard deviation (1-SD) increase in metabolic-equivalent (MET)-minutes/week of self-reported moderate-to-vigorous physical activity were computed using the inverse variance weighted method. A series of sensitivity analyses addressed the potential impact of heterogeneity, pleiotropy, and outliers.

Results

Summary data were available for 122,977 breast cancers and 12,270 endometrial cancers. Genetic predisposition to increased accelerometer-assessed physical activity was associated with lower risk of breast and endometrial cancers. The associations (ORs [95% CI] per 1-SD increase in mean acceleration) were 0.88 (0.85-0.91) for breast cancer and 0.90 (0.83-0.97) for endometrial cancer. In addition, genetic predisposition to increased accelerometer-assessed physical activity was associated with lower risk of ER+ breast cancer. We found no evidence for an association between genetic predisposition to self-reported physical activity and risk of total breast cancer, breast cancer subtypes, or endometrial cancer.

Conclusion and Relevance

This first Mendelian randomization study shows that objectively-assessed physical activity plays a causal role in protecting against breast and endometrial cancers.
DNA-based long-lived reaction-diffusion patterning in a host hydrogel
Authors: Urtel Georg , Estevez-Torres André , Galas Jean-Christophe
Published: September 2019

The development of living organisms is a source of inspiration for the creation of synthetic life-like materials. Embryo development is divided into three stages that are inextricably linked: patterning, differentiation and growth. During patterning, sustained out-of-equilibrium molecular programs interpret underlying molecular cues to create well-defined concentration profiles. Implementing this patterning stage in an autonomous synthetic material is a challenge that at least requires a programmable and long-lasting out-of-equilibrium chemistry compatible with a host material. Here we show that DNA/enzyme reactions can create reaction-diffusion patterns that are extraordinary long-lasting both in solution and inside an autonomous hydrogel. The life-time and stability of these patterns - here traveling fronts and two-band patterns - are significantly increased by blocking parasitic side reactions and by dramatically reducing the diffusion coefficient of specific DNA sequences. Immersed in oil, hydrogels pattern autonomously with limited evaporation, but can also exchange chemical information from other gels when brought in contact. Our primitive metabolic material thus recapitulates two important properties of living matter: a certain degree of autonomy that makes each piece of material an ‘individual’ with its own metabolism and, at the same time, the capacity to interact with other ‘individuals’.
Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model
Authors: Proctor Elizabeth A. , Dineen Shauna M. , Van Nostrand Stephen C. , Kuhn Madison K. , Barrett Christopher D. , Brubaker Douglas K. , Yaffe Michael B. , Lauffenburger Douglas A. , Leon Lisa R.
Published: September 2019

Heat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.

Key points

A signature of pro-coagulation markers predicts circadian core body temperature and levels of organ damage in heat stroke

Changes in coagulopathy-related gene expression are evidenced before histopathological organ damage
On a simple general principle of brain organization
Authors: Velazquez Jose L. Perez , Mateos Diego M. , Erra Ramon Guevara
Published: September 2019

A possible framework to characterise nervous system dynamics and its organization in conscious and unconscious states is introduced, derived from a high level perspective on the coordinated activity of brain cell ensembles. Some questions are best addressable in a global framework and here we build on past observations about the structure of configurations of brain networks in conscious and unconscious states and about neurophysiological results. Aiming to bind some results together into some sort of coherence with a central theme, the scenario that emerges underscores the crucial importance of the creation and dissipation of energy gradients in brain cellular ensembles resulting in maximisation of the configurations in the functional connectivity among those networks that favour conscious awareness and healthy conditions. These considerations are then applied to indicate approaches that can be used to improve neuropathological syndromes.
Computationally Guided Design of Dipeptidyl Peptidase-4 Inhibitors
Authors: Reynolds Lauren C. , Connolly Morgan P. , Siegel Justin B.
Published: September 2019

The Type 2 Diabetes Mellitus (T2DM) epidemic undoubtedly creates a need for the development of new pharmaceuticals. With the goal of generating new therapeutics for this disease, computational studies were conducted to design novel dipeptidyl peptidase-4 (DPP-4) inhibitors. Two candidates, generated by chemical intuition-driven design and bioisosteric replacement, were found to have better docking scores than anagliptin, a currently available diabetes medication.
Deep characterization of the protein lysine acetylation in human gut microbiome and its alterations in patients with Crohn’s disease
Authors: Zhang Xu , Ning Zhibin , Mayne Janice , Deeke Shelley A. , Walker Krystal , Farnsworth Charles L. , Stokes Matthew P. , Mack David , Stintzi Alain , Figeys Daniel
Published: September 2019

Metagenomic and metaproteomic approaches have been used to study the composition and functions of the microbiota. However, no studies have examined post-translational modifications (PTM) on human microbiome proteins at the metaproteome level, and it remains unknown whether the microbial PTM is altered or not in patient microbiome. Herein we used anti-acetyl-lysine (Kac) antibody enrichment strategy and mass spectrometry to characterize the protein lysine acetylation in human microbiome, which successfully identified 35,200 Kac peptides corresponding to 31,821 Kac sites from the microbial or host proteins in human gut microbiome samples. The gut microbial proteins exhibited Kac motifs that were distinct from those of human proteins. Functional analysis showed that microbial Kac proteins were significantly enriched in energy production and abundant in enzymes related to transferases and oxidoreductases. Applying to the analysis of pediatric Crohn’s disease (CD) patient microbiome identified 52 host and 136 microbial protein Kac sites that were differentially abundant in CD versus controls. Interestingly, most of the decreased Kac sites in CD were derived from Firmicutes and most of the increased sites were derived from Bacteroidetes. Forty-six out of the 52 differentially abundant human protein Kac sites were increased in CD patients, including those on calprotectin, lactotransferrin and immunoglobulins. Taken together, this study provides an efficient approach to study the lysine acetylation in microbiome and revealed taxon-specific alterations in the lysine acetylome as well as changes in host protein acetylation levels in intestinal samples during the on-set of disease in CD patients.