bluuebunny/crossref_metadata_2025 huggingface dataset:
EDITORIAL FOREWORD
Authors: Pursley Sara , Baron Beth
Published: October 2013

This issue of IJMES features seven full-length articles and a roundtable on “theorizing violence.” While we were preparing the articles for publication in June and early July, the conflict in Syria was escalating, the Turkish state was suppressing protests in Gezi Park, and the situation in Egypt took a precipitous turn when the military killed more than fifty Muslim Brotherhood supporters. As our colleagues writing in more time-sensitive venues such as Jadaliyya, Facebook, and personal blogs scrambled to keep up with events, we decided to take a broader look at scholarly approaches to the study of violence. For the roundtable, we asked seven political scientists, historians, and anthropologists working on the Middle East and South Asia to reflect on “violence” as a theoretical category across the disciplines. The responses move from introductory reflections on studying, teaching, and writing about violence by our new board member Laleh Khalili, who helped us organize the roundtable, to conceptualizations of violence “from above” employed by colonial, postcolonial, and neoliberal states (Khalili, Daniel Neep), through everyday and crisis-linked forms of sexual violence (Veena Das) and violence “from below,” whether in the forms of communal riots and suicide bombing (Faisal Devji) or self-immolation, hunger strikes, and other acts of self-destruction (Banu Bargu), to reflections on violence and nonviolence in Gezi Park (Yeşim Arat). The roundtable concludes with a broad-sweep analysis of most of the above in relation to (inter)disciplinarity and to Middle Eastern modernity by our board member James McDougall.
DĀRIJAAND CHANGING WRITING PRACTICES IN MOROCCO
Authors: Elinson Alexander E.
Published: October 2013

Social, political, and technological changes have forced changes in the contemporary Moroccan linguistic landscape. In print media, advertising, music, fictional writing, and translation, Moroccan Arabic (dārija) is being written in a variety of ways that point to a shift in perceptions and usage ofdārijain daily Moroccan life. In this article, I provide a discussion of recent developments in the use ofdārijain writing, and discuss how this evolving situation is articulated by intellectuals, journalists, publishers, fiction writers, and translators.
AN ESSENTIAL CENTER–PERIPHERY ELECTORAL CLEAVAGE AND THE TURKISH PARTY SYSTEM
Authors: Wuthrich F. Michael
Published: October 2013

For nearly forty years, scholars have utilized the metanarrative of a center–periphery cleavage first proposed by Şerif Mardin to explain a variety of phenomena in Turkish politics and society. When used to interpret electoral cleavages in the multiparty period, however, a center–periphery cleavage cannot effectively explain electoral outcomes. Focusing on the initial stage of multiparty competition, when the cleavage is often said to have been most salient, this article explores the empirical evidence to show that the concept as commonly employed has actually confounded an effective understanding of electoral behavior in Turkey. Rather than demonstrating a clear electoral division between the elites of the social center and the masses during this period, the article reveals two distinct cross-cutting patron-client strategies used by elite-dominated parties to cater to the rural population. The significant patterns of change in Turkey's electoral outcomes over time further illustrate the need to focus on how political parties and elites accumulate votes—that is, on their vote targeting strategies—rather than rely on static sociopolitical cleavages.
“ADULTS SEE POLITICS AS A GAME”: POLITICS OF KURDISH CHILDREN IN URBAN TURKEY
Authors: Darıcı Haydar
Published: October 2013

This article explores the political subjectivity of Kurdish children in urban Turkey. Often referred to as “stone-throwing children,” since the early 2000s Kurdish children have entered Turkish public discourse as central political actors of the urban Kurdish movement. I suggest that the politicization of children can be understood in the context of transformations in age and kinship systems within the Kurdish community that were shaped by the forced migration of Kurds in the early 1990s. Focusing on the experiences of Kurdish children in the city of Adana, I argue that memories of violence transmitted by displaced parents, combined with the children's experiences of urban life, including exclusion, discrimination, poverty, and state violence, necessitate a reevaluation of how childhood is conceived and experienced within the Kurdish community. In a context where Kurdish adults often have trouble integrating into the urban context, their children frequently challenge conventional power relations within their families as well as within the Kurdish movement. In contrast to a dominant Turkish public discourse positing that these children are being abused by politicized adults, I contend that Kurdish children are active agents who subvert the agendas and norms of not only Turkish but also Kurdish politics. The article analyzes the ways Kurdish children are represented in the public discourse, how they narrate and make sense of their own politicization, and the relationship between the memory and the postmemory of violence in the context of their mobilization.
Thinking about Violence
Authors: Khalili Laleh
Published: October 2013

Colleagues with whom I spoke about this piece had one of two responses: “Why do you want to feed the flames of cliché and prejudice about violence in the Middle East?” and “Surely, there has been no theorization of violence in the Middle East.” Regarding the first response, I agree that thinking about violence in the Middle East can be a fraught enterprise. This is because a hysterical mainstream narrative locates the sources of violence in or emanating from the region in Islam(ism) or attributes it to some half-baked but remarkably persistent cultural explanations (tribalism, ancient hatreds, cycles of violence, etc.) which uncomfortably echo the racism of an earlier scholarly era. But enough innovative works have emerged on violence that we can move—at least in our scholarly conversations—beyond this terrain of prejudice and paranoia.
War, State Formation, and Culture
Authors: Neep Daniel
Published: October 2013

Historical sociology has long been concerned with the study of organized state violence. Since the mid-1970s, a substantial body of work has come to focus on the importance of warfare to historical processes of state formation. The first generation of this literature proposed that the relentless existential struggle between the warring polities of medieval Europe had favored the survival of states that could adopt ever more efficient means to extract and mobilize resources from the local population to feed the war effort. Early states therefore evolved the institutions to collect taxes and administer territory largely as a functional byproduct of interstate military competition. From this perspective, the logic of war making was the driving force behind the rise of the modern state in Europe.
Violence, Crisis, and the Everyday
Authors: Das Veena
Published: October 2013

An important issue in considering violence at both the conceptual and empirical levels is the question of what counts as “violence” and how it is acknowledged. In many polities of the Middle East, including Palestine, Iraq, and Afghanistan, there is no clear boundary between war and peace. Conflicts have lasted over a long period and even the project of securing a future in which the struggle for decolonization and political autonomy can be kept alive faces enormous hurdles as everyday life is corroded by betrayals, accusations, and the sheer exhaustion of keeping political energies from waning. Most acute observers of prolonged conflicts recognize the corrosive effects of these conflicts on everyday life. In this brief thought piece, I want to reflect on one aspect of the problem: that of the relation between sexual violence as an aspect of dramatic and spectacular violence—in wars (including modern ones), pogroms against ethnic or religious minorities, or episodes of lethal riots between sectarian groups—and everyday forms of sexual violence that could be both part of the public domain and constitutive of domestic intimacy. Said otherwise, I am interested in how experience of violence travels from one threshold of life to another.
Communities of Violence
Authors: Devji Faisal
Published: October 2013

Violence is a word seemingly meant for theorizing, being as abstract and thus as capacious as any category can be. And indeed the history of its use has only confirmed the all-encompassing character of violence, which can now name almost any kind of action or affect: physical, psychological, and even ideological. And yet this term is also deployed to name the most distinctive and visceral forms of cruelty and suffering, such that it is difficult to treat it merely as another abstract category. Shifting uncomfortably between the particularity of pain and the generality of an intellectual category, violence has until recently been ill served by scholarship. The necessities of justice, for example, have meant that violence is rarely the subject of law in its own right, but used only as a euphemism for some degree of murder or charge of battery. And since historians are especially seduced by legal terminology, perhaps because they have traditionally described and justified power, their efforts to mimic the law by finding some party responsible for something have tended not to deal productively with violence.
Thought Reform and the Unreformable: Reeducation Centers and the Rhetoric of Opposition in the Early People's Republic of China
Authors: Smith Aminda M.
Published: October 2013

This essay explores records from Beijing's efforts to intern and reform the city's “lumpenproletariat” after 1949. Connecting these reports to central government directives about national thought reform policy, I show that reeducators and their superiors discoursed in detail about the existence of resisters, who opposed and defied the government, but whom reformatory staff explicitly labeled as non-enemies. The case of Beijing reformatories suggests that anti-state, but non-counterrevolutionary resistance was an important symbolic and rhetorical category, central to the Chinese Communist Party's articulation of its own purpose. In the context of reeducation, opposition to the party-state constituted evidence of a founding “truth”: feudal, imperialist, and capitalist oppression had so damaged the Chinese nation that only a radical and revolutionary transformation could save it. Over the course of the 1950s, reading and analyzing resistance in this way led policy makers to redefine “The People” as well as the social place of individuals accused of activities like prostitution, begging, and petty crime.
The influence of alkaline earth metal equilibria on the rheological, melting and textural properties of Cheddar cheese
Authors: Cooke Darren R , McSweeney Paul LH
Published: October 2013

The total calcium content of cheese, along with changes in the equilibrium between soluble and casein (CN)-bound calcium during ripening can have a major impact on its rheological, functional and textural properties; however, little is known about the effect of other alkaline earth metals. NaCl was partially substituted with MgCl2 or SrCl2 (8·7 and 11·4 g/kg curd, respectively) at the salting stage of cheesemaking to study their effects on cheese. Three cheeses were produced: Mg supplemented (+Mg), Sr supplemented (+Sr) and a control Cheddar cheese. Ca, Mg and Sr contents of cheese and expressible serum obtained therefrom were determined by atomic absorption spectroscopy. Addition of Mg2+ or Sr2+ had no effect on % moisture, protein, fat and extent of proteolysis. A proportion of the added Mg2+ and Sr2+ became CN-bound. The level of CN-bound Mg was higher in the +Mg cheese than the control throughout ripening. The level of CN-bound Ca and Mg decreased during ripening in all cheeses, as did % CN-bound Sr in the +Sr cheese. The presence of Sr2+ increased % CN-bound Ca and Mg at a number of ripening times. Adding Mg2+ had no effect on % CN-bound Ca. The +Sr cheese exhibited a higher G′ at 70 °C and a lower LTmax than the control and +Mg cheeses throughout ripening. The +Sr cheese had significantly lower meltability compared with the control and +Mg cheeses after 2 months of ripening. Hardness values of the +Sr cheese were higher at week 2 than the +Mg and control cheeses. Addition of Mg2+ did not influence the physical properties of cheese. Supplementing cheese with Sr appeared to have effects analogous to those previously reported for increasing Ca content. Sr2+ may form and/or modify nanocluster crosslinks causing an increase in the strength of the para-casein matrix.
Patient information leaflet on mastoid surgery risks: assessment of readability and patient understanding
Authors: Pringle M B , Natesh B G , Konieczny K M
Published: October 2013

Introduction:

It is important that patients have a good understanding of surgery-related risks, particularly for mastoid surgery, which exposes patients to the risk of very serious complications, despite addressing conditions which often have only minor symptoms.

Materials and methods:

A patient information leaflet describing the risks of mastoid surgery was prepared. However, the Hospital Patient Advice and Liaison Services team thought it was too long and complicated. It was introduced unchanged. Fifty-four consecutive mastoidectomy patients were given a questionnaire asking for their opinion of the leaflet. The leaflet was also assessed with readability formulae and the Ensuring Quality Information for Patients tool.

Results and analysis:

Ninety-eight per cent of respondents thought the leaflet's writing style was easy to understand. The majority (96 per cent) thought the length was ‘just right’. The 7 readability formulae used established readability at a grade 9 level (i.e. appropriate for a reading age of 13–15 years). The Ensuring Quality Information for Patients score was 87.5 per cent.

Discussion:

Despite the drive to simplify patient information leaflets, quite detailed information is sometimes required. A style which is too simple may be perceived as patronising and may encourage patients to underestimate potential risks. It is important to ask patients their opinion.
Precarious status of the Endangered dholeCuon alpinusin the high elevation Eastern Himalayan habitats of Khangchendzonga Biosphere Reserve, Sikkim, India
Authors: Bashir Tawqir , Bhattacharya Tapajit , Poudyal Kamal , Roy Manjari , Sathyakumar Sambandam
Published: October 2013

During 2008–2010 we investigated the ecology of the Endangered dhole or wild dogCuon alpinusin Khangchendzonga Biosphere Reserve in the Eastern Himalaya in Sikkim, India. We conducted camera trapping (n = 71 sites, 6,278 camera-days) and sign surveying along trails (n = 24; 629.43 km of effort) to assess the relative abundance, distribution and activity pattern of the dhole. Morphological characteristics evident in the 61 camera-trap photographs indicate that the dhole population in the Reserve may be the rare and genetically distinct subspeciesC. alpinus primaevus. We detected dholes over a wide elevation range (2,501–4,100 m) that encompassed the upper temperate, subalpine, and alpine scrub zones. Dholes were diurnal, with peak activity at 08.00–10.00. Analysis of 41 scats indicated a diet comprising mainly mountain ungulates, rodents and pikasOchotonasp. Although the frequency of occurrence of rodents was highest (32%) in the scats, 98.7% of the total biomass consumed was of mountain ungulates. Historical reports (1888–1894) indicated that the dhole was formerly abundant in Sikkim but was hunted to meet the high demand for its alleged medicinal properties. With no information on the status of the dhole in Sikkim for over a century, our study suggests that the species is now rare in the Reserve. To aid the conservation of the dhole and its main ungulate prey species extensive research and monitoring are required in the Reserve and elsewhere in the Eastern Himalaya.
ARE ETHICISTS ANY MORE LIKELY TO PAY THEIR REGISTRATION FEES AT PROFESSIONAL MEETINGS?
Authors: Schwitzgebel Eric
Published: October 2013

Lists of paid registrants at Pacific Division meetings of the American Philosophical Association from 2006–2008 were compared with lists of people appearing as presenters, commentators or chairs on the meeting programme those same years. These were years in which fee payment depended primarily on an honour system rather than on enforcement. Seventy-four per cent of ethicist participants and 76% of non-ethicist participants appear to have paid their meeting registration fees: not a statistically significant difference. This finding of no difference survives scrutiny for several possible confounds. Thus, professional ethicists seem no less likely to free-ride in this context than do philosophers not specializing in ethics. These data fit with other recent findings suggesting that on average professional ethicists behave no morally better than do professors not specializing in ethics.
PUBLIC POLICY AND THE CONDITIONAL VALUE OF HAPPINESS
Authors: van der Rijt Jan-Willem
Published: October 2013

This paper examines the increasingly popular view that new insights from the science of subjective well-being (SSWB) should play a prominent role in the determination of public policy. Though there are instrumental reasons for caring about societal happiness too, these political aspirations of the SSWB appear to be mostly intrinsically motivated. As the intrinsic value of happiness is endorsed across the political–philosophical spectrum, there is some initial plausibility to the expectation that it should not be too difficult to develop intrinsically motivated policies that can count on widespread support. This paper argues, however, that intrinsically motivated policies based on SSWB findings will always be highly controversial. This is because, although happiness is widely held to beintrinsicallyvaluable, it is usually not deemedunconditionallyvaluable. By exploring the policy implications of three different views of this conditionality – happiness as a fitting response to the state of the world, authenticity, and merit – it is shown that different views of the conditionality of the intrinsic value of happiness have widely diverging policy implications, which greatly undermines the political aspirations of the SSWB.
Powder diffraction data of the Ho2AlGe3 ternary compound
Authors: Liang Liuqing , Qin Ming , Lu Zhao , Li Degui , He Bing , Zeng Lingmin
Published: October 2013

A new ternary compound Ho2AlGe3 was synthesized and studied by means of X-ray powder diffraction technique. The powder pattern of Ho2AlGe3 was indexed and refined, giving an orthorhombic structure, space group Pnma (No. 62) with the Y2AlGe3 structure type: a = 6.743 98(8) Å, b = 4.163 73(5) Å, c = 17.5834(2) Å, V = 493.74 Å3, Z = 4, ρx = 7.73 g cm−3, F30 = 202.7 (0.004, 37), and RIR = 1.21.
Tilt angles and positive response of head-up tilt test in children with orthostatic intolerance
Authors: Lin Jing , Wang Yuli , Ochs Todd , Tang Chaoshu , Du Junbao , Jin Hongfang
Published: October 2013

This study aimed at examining three tilt angle-based positive responses and the time to positive response in a head-up tilt test for children with orthostatic intolerance, and the psychological fear experienced at the three angles during head-up tilt test. A total of 174 children, including 76 boys and 98 girls, aged from 4 to 18 years old (mean 11.3±2.8 years old), with unexplained syncope, were randomly divided into three groups, to undergo head-up tilt test at the angles of 60°, 70° and 80°, respectively. The diagnostic rates and times were analysed, and Wong–Baker face pain rating scale was used to access the children’s psychological fear. There were no significant differences in diagnostic rates of postural orthostatic tachycardia syndrome and vasovagal syncope at different tilt angles during the head-up tilt test (p>0.05). There was a significant difference, however, in the psychological fear at different tilt angles utilising the Kruskal–Wallis test (χ2=36.398, p<0.01). It was mildest at tilt angle 60° utilising the Kolmogorov–Smirnov test (p<0.01). A positive rank correlation was found between the psychological fear and the degree of tilt angle (rs=0.445, p<0.01). Positive response appearance time was 15.1±14.0 minutes at 60° for vasovagal syncope children. There was no significant difference in the time to positive response, at different tilt angles during the head-up tilt test for vasovagal syncope or for postural orthostatic tachycardia syndrome. Hence, it is suggested that a tilt angle of 60° and head-up tilt test time of 45 minutes should be suitable for children with vasovagal syncope.
LENS SPACE SURGERIES ALONG CERTAIN 2-COMPONENT LINKS RELATED WITH PARK’S RATIONAL BLOW DOWN, AND REIDEMEISTER-TURAEV TORSION
Authors: KADOKAMI TERUHISA , YAMADA YUICHI
Published: October 2013

We study lens space surgeries along two different families of 2-component links, denoted by${A}_{m, n} $and${B}_{p, q} $, related with the rational homology$4$-ball used in J. Park’s (generalized) rational blow down. We determine which coefficient$r$of the knotted component of the link yields a lens space by Dehn surgery. The link${A}_{m, n} $yields a lens space only by the known surgery with$r= mn$and unexpectedly with$r= 7$for$(m, n)= (2, 3)$. On the other hand,${B}_{p, q} $yields a lens space by infinitely many$r$. Our main tool for the proof are the Reidemeister-Turaev torsions, that is, Reidemeister torsions with combinatorial Euler structures. Our results can be extended to the links whose Alexander polynomials are same as those of${A}_{m, n} $and${B}_{p, q} $.
PSI: A Computational Architecture of Cognition, Motivation, and Emotion
Authors: Dörner Dietrich , Güss C. Dominik
Published: October 2013

This article describes PSI theory, which is a formalized computational architecture of human psychological processes. In contrast to other existing theories, PSI theory not only models cognitive, but also motivational and emotional processes and their interactions. The article starts with a brief overview of the theory showing the connections between its different parts. We then discuss the theory's components in greater detail. Key constructs and processes are the five basic human needs, the satisfaction of needs using the cognitive system, including perception, schemas in memory, planning, and action. Furthermore, emotions are defined and the role of emotions in cognitive and motivational processes is elaborated, referring to a specific example. The neural basis of the PSI theory is also highlighted referring to the “quad structure,” to specific brain areas, and to thinking as scanning in a neural network. Finally, some evidence for the validity of the theory is provided.
Nucleosome sliding by Chd1 does not require rigid coupling between DNA‐binding and ATPase domains
Authors: Nodelman Ilana M , Bowman Gregory D
Published: October 2013

Chromatin remodellers are ATP‐dependent motor proteins that physically reposition and reorganize nucleosomes. Chd1 and Iswi‐type remodellers possess a DNA‐binding domain (DBD) needed for efficient nucleosome mobilization; however, it has not been clear how this domain physically contributes to remodelling. Here we show that the Chd1 DBD promotes nucleosome sliding simply by tethering the remodeller to nucleosome substrates. Nucleosome sliding activity was largely resistant to increasing length and flexibility of the linker connecting the DBD and ATPase motor, arguing that the ATPase motor does not shift DNA onto the nucleosome by pulling on the DBD.
hPrimpol1/CCDC111 is a human DNA primase‐polymerase required for the maintenance of genome integrity
Authors: Wan Li , Lou Jiangman , Xia Yisui , Su Bei , Liu Ting , Cui Jiamin , Sun Yingying , Lou Huiqiang , Huang Jun
Published: October 2013

Prim‐pol is a recently identified DNA primase‐polymerase belonging to the archaeao‐eukaryotic primase (AEP) superfamily. Here, we characterize a previously unrecognized prim‐pol in human cells, which we designate hPrimpol1 (human primase‐polymerase 1). hPrimpol1 possesses primase and DNA polymerase activities in vitro, interacts directly with RPA1 and is recruited to sites of DNA damage and stalled replication forks in an RPA1‐dependent manner. Cells depleted of hPrimpol1 display increased spontaneous DNA damage and defects in the restart of stalled replication forks. Both RPA1 binding and the primase activity of hPrimpol1 are required for its cellular function during DNA replication. Our results indicate that hPrimpol1 is a novel factor involved in the response to DNA replication stress.
Toward a role model
Authors: Sharan Roded
Published: October 2013

With ever‐growing amounts of 'omics data, the challenge is to develop an automatic modelling pipeline that receives as input large‐scale data pertaining to the system of interest and outputs a complete, logical model that maximizes the fit to the given data.
Molecular fossils probe life's origins
Authors: Hunter Philip
Published: October 2013

Molecular fossils allow evolutionary biologists to look deep into the history of life on the Earth, far beyond the fossil record and possibly to the first living organisms.
Quantum-criticality-induced strong Kerr nonlinearities in optomechanical systems
Authors: Lü Xin-You , Zhang Wei-Min , Ashhab Sahel , Wu Ying , Nori Franco
Published: October 2013

We investigate a hybrid electro-optomechanical system that allows us to realize controllable strong Kerr nonlinearities even in the weak-coupling regime. We show that when the controllable electromechanical subsystem is close to its quantum critical point, strong photon-photon interactions can be generated by adjusting the intensity (or frequency) of the microwave driving field. Nonlinear optical phenomena, such as the appearance of the photon blockade and the generation of nonclassical states (e.g., Schrödinger cat states), are demonstrated in the weak-coupling regime, making the observation of strong Kerr nonlinearities feasible with currently available optomechanical technology.
Maintenance of pluripotency in mouse ES cells without Trp53
Authors: Shigeta Masaki , Ohtsuka Satoshi , Nishikawa-Torikai Satomi , Yamane Mariko , Fujii Setsuko , Murakami Kazuhiro , Niwa Hitoshi
Published: October 2013

Tumor suppressor Trp53 works as a guardian of the genome in somatic cells. In mouse embryonic stem (ES) cells, it was reported that Trp53 represses pluripotency-associated transcription factor Nanog to induce differentiation. However, since Trp53-null mice develop to term, Trp53 is dispensable for both the maintenance and differentiation of the pluripotent stem cell population in vivo, suggesting the differential functions of Trp53 in ES cells and embryos. To reveal the basis of this discrepancy, here we established a new line of Trp53-null ES cells by sequential gene targeting and evaluated their ability to differentiate in vitro and in vivo. We found that Trp53-null ES cells had defects in differentiation in vitro as reported previously, whereas they were able to contribute to normal development in chimeric embryos. These data indicated that the requirement of Trp53 for maintaining and executing the ES pluripotency is not absolute.
Effects of adaptive degrees of trust on coevolution of quantum strategies on scale-free networks
Authors: Li Qiang , Chen Minyou , Perc Matjaž , Iqbal Azhar , Abbott Derek
Published: October 2013

We study the impact of adaptive degrees of trust on the evolution of cooperation in the quantum prisoner's dilemma game. In addition to the strategies, links between players are also subject to evolution. Starting with a scale-free interaction network, players adjust trust towards their neighbors based on received payoffs. The latter governs the strategy adoption process, while trust governs the rewiring of links. As soon as the degree of trust towards a neighbor drops to zero, the link is rewired to another randomly chosen player within the network. We find that for small temptations to defect cooperators always dominate, while for intermediate and strong temptations a single quantum strategy is able to outperform all other strategies. In general, reciprocal trust remains within close relationships and favors the dominance of a single strategy. Due to coevolution, the power-law degree distributions transform to Poisson distributions.
Cysteine-reactive chemical probes based on a modular 4-aminopiperidine scaffold
Authors: Couvertier Shalise M. , Weerapana Eranthie
Published: October 2013

Tri-substituted 4-aminopiperidine provides a modular and versatile scaffold for the generation of cysteine-reactive probes for diverse proteins.
Genetic variation and gender determine bradykinin type 1 receptor responses in human tissue: implications for the ACE-inhibitor-induced effects in patients with coronary artery disease
Authors: Wu Haiyan , Roks Anton J. M. , Leijten Frank P. J. , Garrelds Ingrid M , Musterd-Bhaggoe Usha M. , van den Bogaerdt Antoon J. , de Maat Moniek P. M. , Simoons Maarten L. , Danser A. H. Jan , Oeseburg Hisko
Published: October 2013

The efficacy of the ACE (angiotensin-converting enzyme) inhibitor perindopril in coronary artery disease [EUROPA (European trial on reduction of cardiac events with perindopril in stable coronary artery disease) study] is associated with the rs12050217 A/G single nucleotide polymorphism in the B1 receptor (bradykinin type 1 receptor) gene. To investigate the underlying mechanism, we examined the effect of this polymorphism on B1-receptor-mediated coronary artery dilation and peripheral blood mononuclear cell activation. Vasorelaxant responses of human coronary microarteries from subjects without coronary disease to des-Arg9-bradykinin and to bradykinin were studied in organ bath experiments. Des-Arg9-bradykinin responses were endothelium-dependent and exclusively mediated by B1 receptors, whereas responses to bradykinin were induced through B2 receptors (bradykinin type 2 receptors). The presence of the G allele reduced the response to 3×10−8 mol/l des-Arg9-bradykinin by 29% [AA (n=13) compared with AG/GG (n=8); P<0.03], and tended to lower concentration-related responses (P=0.065) to this agonist, whereas the responses to bradykinin were unaffected by the rs12050217 genotype. In freshly obtained human mononuclear cells 1 μmol/l des-Arg9-bradykinin increased expression of the pro-inflammatory factors CXCL5 (CXC chemokine ligand 5) and IL6 (interleukin-6). These responses were not affected by genotype and exclusively occurred in blood cells from women, correlating (in the case of CXCL5) with their plasma 17β-oestradiol levels (r2=0.32, P=0.02; n=17). IL-1β (interleukin-1β) increased CXCL5 and IL6 expression in both genders, and this response was not associated with 17β-oestradiol levels. The gender difference in responses to B1 receptor stimulation in blood mononuclear cells implies possible gender differences in the response to ACE inhibitor therapy, which needs to be studied more comprehensively. The observed decrease in coronary vasodilator response might contribute to the impaired treatment response to perindopril of G allele carriers found in the EUROPA study.
Dynamic model for the coordination of two enhancers of
broad
by EGFR signaling
Authors: Cheung Lily S. , Simakov David S. A. , Fuchs Alisa , Pyrowolakis George , Shvartsman Stanislav Y.
Published: October 2013

Significance

Temporal regulation of a typical developmental control gene depends on multiple enhancers, which makes it important to understand how enhancers coordinate their activities in time. We describe a mechanism for such coordination in
Drosophila
oogenesis, where the expression of the transcription factor Broad depends on sequential activities of two enhancers. The early enhancer is essential for activity of the late one. To explain this requirement, we propose a mechanism based on a network with feedforward and feedback loops. This network interprets and modulates the epidermal growth factor receptor (EGFR) signaling gradient that controls both enhancers. Experiments and computational modeling show that understanding Broad expression is impossible without simultaneously considering two enhancers, a dynamic gradient, and a network with extracellular and intracellular components.
Placebo improves pleasure and pain through opposite modulation of sensory processing
Authors: Ellingsen Dan-Mikael , Wessberg Johan , Eikemo Marie , Liljencrantz Jaquette , Endestad Tor , Olausson Håkan , Leknes Siri
Published: October 2013

Significance

Placebo effects illustrate the power of the human brain; simply expecting an improvement can alter pain processing and produce analgesia. We induced placebo improvement of both negative and positive feelings (painful and pleasant touch) in healthy humans, and compared the brain processing using functional MRI. Pain reduction dampened sensory processing in the brain, whereas increased touch pleasantness increased sensory processing. Neurocircuitry associated with emotion and reward underpinned improvement of both pain and pleasant touch. Our findings suggest that expectation of improvement can recruit common neurocircuitry, which up- or down-regulates sensory processing, depending on whether the starting point is painful or pleasant. These results promote widening the scope of medical research to improvement of positive experiences and pleasure.
Direct transfer of graphene onto flexible substrates
Authors: Martins Luiz G. P. , Song Yi , Zeng Tingying , Dresselhaus Mildred S. , Kong Jing , Araujo Paulo T.
Published: October 2013

Significance

We investigated a lamination technique for directly transferring graphene onto various flexible substrates, which does not require using polymethylmethacrylate (PMMA) as an intermediate transfer membrane. Our studies reveal that the method is most effective on hydrophobic substrates with low glass transition temperature. For substrates like paper or cloth that do not meet these criteria, a polymer such as PMMA can be used as a surface modifier or as an adhesive to ensure successful transfer. Having graphene on substrates such as paper or cloth will open up wide opportunities for ubiquitous or wearable electronics, and we anticipate our work will have significant impact on the research community.
Testing the cation-hydration effect on the crystallization of Ca–Mg–CO
3
systems
Authors: Xu Jie , Yan Chao , Zhang Fangfu , Konishi Hiromi , Xu Huifang , Teng H. Henry
Published: October 2013

Significance

Magnesium-bearing carbonate minerals play critical roles in the health and function of the Earth system because they constitute a significant fraction of lithosphere carbon reservoir and build skeletal structures for the majority of marine invertebrate organisms. Despite wide occurrence, high-Mg and sole-Mg phases such as dolomite ([Ca,Mg]CO
3
) and magnesite (MgCO
3
) prove virtually impossible to be crystallized under ambient conditions. It has long been believed that Mg
2+
hydration is the cause for such a geological mystery. Here, we probe this hypothesis by investigating Ca–Mg–CO
3
precipitation in the absence of water and find direct proof suggesting the existence of a more intrinsic crystallization barrier. These findings provide a perspective augmenting our understanding in carbonate mineralogy, biomineralization, and mineral-carbonation processes.
A test of Darwin's naturalization hypothesis in the thistle tribe shows that close relatives make bad neighbors
Authors: Park Daniel S. , Potter Daniel
Published: October 2013

Significance

Invasive species negatively impact both natural ecosystems and human society and are notoriously difficult to control once established. Thus, identifying potentially invasive taxa and preventing their dislocation is the most efficient management method. Darwin’s naturalization hypothesis, which predicts that the less closely related to native flora species are, the more likely they are to succeed as invaders, is tested here with an unprecedentedly thorough molecular phylogenetic approach, examining >100,000 phylogenies of the weed-rich thistle tribe Cardueae. Branch lengths between taxa were used as measures of evolutionary relatedness. Results show that invasive thistles are more closely related to natives than noninvasive introduced thistles, suggesting they share preadaptive traits with the natives that make them more likely to succeed as invaders.
Single-molecule imaging of the functional crosstalk between surface NMDA and dopamine D1 receptors
Authors: Ladepeche Laurent , Dupuis Julien P. , Bouchet Delphine , Doudnikoff Evelyne , Yang Luting , Campagne Yohan , Bézard Erwan , Hosy Eric , Groc Laurent
Published: October 2013

Significance

Dopamine receptor signaling in the brain participates in memory encoding through the regulation of glutamatergic signaling. Here we provide evidence that single dopamine D1 receptors are highly dynamic at the surface of hippocampal neurons. In addition, these receptors, together with glutamatergic NMDA receptors, form surface clusters in the vicinity of glutamate synapses, providing a strategically located reservoir pool from which they can be laterally redistributed during synaptic adaptations. The plasma membrane and receptor dynamics thus appear as an important level of the glutamate–dopamine interplay.
Reward-based hypertension control by a synthetic brain–dopamine interface
Authors: Rössger Katrin , Charpin-El Hamri Ghislaine , Fussenegger Martin
Published: October 2013

Significance

Essential activities such as feeding and reproduction as well as social, emotional, and mental behavior are reinforced by the brain’s reward system. Pleasure status directly correlates with dopamine levels released in the brain. Because dopamine leaks into the bloodstream via the sympathetic nervous system, brain and blood dopamine levels are interrelated. We designed a synthetic dopamine sensor-effector device that enables engineered human cells, insulated by immunoprotective microcontainers and implanted into the abdomen of mice, to monitor blood-dopamine levels and drive dopamine-dependent secretion of product proteins in pleasure situations associated with palatable food, drugs, or sexual arousal. Hypertensive animals treated with this device, which produces a clinically licensed antihypertensive peptide, had their high blood pressure corrected when exposed to sexual arousal.
Loss of estrogen-related receptor α promotes hepatocarcinogenesis development via metabolic and inflammatory disturbances
Authors: Hong Eui-Ju , Levasseur Marie-Pier , Dufour Catherine R. , Perry Marie-Claude , Giguère Vincent
Published: October 2013

Significance

This study shows that absence of the orphan nuclear receptor estrogen-related receptor α (ERRα), a master regulator of cellular energy metabolism, predisposes mice to hepatocellular cancer development when exposed to a known carcinogen. Biochemical and metabolomics studies revealed that loss of ERRα promotes hepatocyte necrosis over apoptosis in response to a carcinogen due to a deficiency in energy production. In addition, we demonstrate that loss of ERRα-dependent regulation of the nuclear factor κB (NF-κB) inhibitor IκBα leads to enhanced NF-κB activity and cytokine gene activation. These findings have particular biological significance in view that rapamycin, a drug currently in use in various clinical settings, has been shown recently to decrease ERRα protein levels and activity in mouse liver.
Bispecific small molecule–antibody conjugate targeting prostate cancer
Authors: Kim Chan Hyuk , Axup Jun Y. , Lawson Brian R. , Yun Hwayoung , Tardif Virginie , Choi Sei Hyun , Zhou Quan , Dubrovska Anna , Biroc Sandra L. , Marsden Robin , Pinstaff Jason , Smider Vaughn V. , Schultz Peter G.
Published: October 2013

Significance

We have developed a semisynthetic method for the production of bispecific antibody-like therapeutics consisting of a small molecule targeting moiety conjugated to an antibody. A highly selective prostate-specific membrane antigen-binding ligand was site specifically conjugated to a mutant α cluster of differentiation 3 (αCD3) Fab containing an unnatural amino acid with orthogonal chemical reactivity. The optimized conjugate showed potent in vitro activity, good serum half-life, and potent in vivo activity in prostate cancer xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.
Putative megaenzyme DWA1 plays essential roles in drought resistance by regulating stress-induced wax deposition in rice
Authors: Zhu Xiaoyi , Xiong Lizhong
Published: October 2013

Significance

Cuticular wax on plant leaves plays an important role in preventing water loss from drought stress. However, the genetic control of wax deposition under drought stress conditions has not been characterized. In this paper, a very large Drought-Induced Wax Accumulation 1
(
DWA1) protein (2,391 aa in length) controlling the drought-induced wax load on leaves was characterized in rice, one of the most important crops. The DWA1 protein contains a multienzyme-like structure, including a prokaryotic nonribosomal peptide synthetase (NRPS)-like module and is conserved in vascular plants. Interestingly, the NRPS-like module with an AMP-binding domain can activate long-chain fatty acids for wax biosynthesis. This finding may have significant implications for improving the drought resistance of crop varieties through modifying wax biosynthesis.
Development of socio-emotional competence in bonobos
Authors: Clay Zanna , de Waal Frans B. M.
Published: October 2013

Significance

Across human development, individuals better able to manage their own emotions show greater social competence and more empathic concern for others. To test this interplay between social and emotional skills in one of our closest relatives, we collected behavioral measures on bonobos (
Pan paniscus
) with different rearing backgrounds at a forested sanctuary in Africa. Young bonobos showed the same connection between the ability to regulate their own emotions and social competence, such as developing friendships and concern for others. Mother-reared juveniles performed far better in this regard than juveniles orphaned at a young age, thus highlighting the importance of the mother–offspring bond. Our results support a shared socio-emotional framework for human and nonhuman primate behavior.
Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+regulatory T cells, evoking antitumor immune responses in humans
Authors: Sugiyama Daisuke , Nishikawa Hiroyoshi , Maeda Yuka , Nishioka Megumi , Tanemura Atsushi , Katayama Ichiro , Ezoe Sachiko , Kanakura Yuzuru , Sato Eiichi , Fukumori Yasuo , Karbach Julia , Jäger Elke , Sakaguchi Shimon
Published: October 2013

Significance

Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a critical role in suppressing antitumor immune responses. Here we found that, compared with peripheral blood T cells, tumor-infiltrating T cells contained a higher frequency of effector Tregs, which are defined as FOXP3hiand CD45RA−, terminally differentiated, and most suppressive. Effector Treg cells, but not FOXP3loand CD45RA+naïve Treg cells, predominantly expressed C-C chemokine receptor 4 (CCR4) in both cancer tissues and peripheral blood. In vivo or in vitro anti-CCR4 mAb treatment selectively depleted effector Treg cells and efficiently induced tumor-antigen-specific CD4+and CD8+T cells. Thus, cell-depleting anti-CCR4 mAb therapy is instrumental for evoking and enhancing tumor immunity in humans via selectively removing effector-type FOXP3+Treg cells.
MDMX contains an autoinhibitory sequence element
Authors: Bista Michal , Petrovich Miriana , Fersht Alan R.
Published: October 2013

Significance

The protein MDMX is an important negative regulator of the tumor suppressor p53 in normal cells and can become a powerful oncogene. Previous studies on isolated protein fragments established that the N-terminal domain of MDMX binds tightly to the N-terminal domain of p53 and inhibits it. We now find that full-length MDMX contains a regulatory element (the “WWW element”) that binds to its own N-terminal domain and prevents MDMX from binding to p53. This autoinhibition introduces a new level of regulation of MDMX, whereby accessory proteins may sequester the WWW sequence and reactivate MDMX, and may explain why a variant of MDMX that lacks the WWW sequence, which is found in some cancer cells, might be oncogenic.
MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9
Authors: Chai Sunghee , Cambronne Xiaolu A. , Eichhorn Stephen W. , Goodman Richard H.
Published: October 2013

Significance

Most brain regions comprise numerous neural cell types that are distinct in function and molecular characteristics. We examined microRNA-134 (miR-134) activity in cortical cultures using a microRNA sensor and discovered that miR-134 was induced in response to neuronal activity in somatostatin- and calretinin-expressing interneurons but not in pyramidal neurons. We identified the palmitoylation enzyme DHHC9 as a direct target of miR-134 and showed that it contributed to the regulation of H-Ras in somatostatin interneurons. H-Ras is a signaling molecule crucial for neuronal development and function. This study uncovered an activity-dependent miR-134 regulatory pathway in cortical interneurons that can potentially affect membrane localization of multiple signaling molecules.
Pten loss in the bone marrow leads to G-CSF–mediated HSC mobilization
Authors: Tesio Melania , Oser Gabriela M. , Baccelli Irène , Blanco-Bose William , Wu Hong , Göthert Joachim R. , Kogan Scott C. , Trumpp Andreas
Published: October 2013

The phosphatase and tumor suppressor PTEN inhibits the phosphoinositol-3-kinase (PI3K) signaling pathway and plays a key role in cell growth, proliferation, survival, and migration. Pten conditional deletion using MxCre or Scl-CreERT leads to splenomegaly and leukemia formation, which occurs after the relocation of normal hematopoietic stem cells (HSCs) from the bone marrow to the spleen. Unexpectedly, dormant HSCs in the bone marrow do not enter the cell cycle upon Pten loss, they do not lose self-renewal activity, and they are not exhausted. Instead, Pten deficiency causes an up-regulation of the PI3K pathway in myeloid cells, but not in HSCs. Strikingly, myeloid cells secrete high levels of G-CSF upon Pten loss, leading to the mobilization of HSCs from the bone marrow and accumulation in the spleen. After deletion of Pten in mice lacking G-CSF, the splenomegaly, myeloproliferative disease, and splenic HSC accumulation are rescued. Our data show that although PTEN has little if any role in normal HSCs, it is essential to prevent overt G-CSF production by myeloid and stromal cells which otherwise causes HSCs to relocate to the spleen followed by lethal leukemia initiation.