bluuebunny/crossref_metadata_2025 huggingface dataset:
Do voters prefer gender stereotypic candidates? evidence from a conjoint survey experiment in Japan
Authors: Ono Yoshikuni , Yamada Masahiro
Published: October 2018

The striking under-representation of women in Japan has been partly attributed to gender stereotypes and prejudice toward female leadership among voters. We examine whether and to what extent candidates get rewarded or punished when they deviate from the behavioral expectations associated with their gender roles and images. Our conjoint experiment results in Japan demonstrate that not only are female candidates disadvantaged compared to their male counterparts, but also that they could lose support when they diverge from gender-based behavioral expectations. Our findings suggest that female candidates face a difficult dilemma in that they must weigh the cost of losing support for failing to conform to gender-based expectations, against the general loss of support they would incur for conforming to these expectations.
Indirect Pathways of Self-Interest and the TPP
Authors: Tuxhorn Kim-Lee
Published: October 2018

Do consumer and producer considerations influence support for future trade agreements and, if so, how? Prior research has pitted self-interest-based explanations of trade preferences against perception-based explanations, finding limited empirical support for the self-interest hypothesis. Instead of treating perceptions and self-interest as competing explanations, we construct a theoretical model with perceptions of trade as a mediating factor linking self-interest and support for prospective free trade agreements (FTAs). Using new survey data collected by the Asia Pacific Foundation of Canada, we examine how two distinct forms of self-interest (consumer and producer considerations) can indirectly shape attitudes toward the Trans-Pacific Partnership (TPP). We find that the impact of respondents' income level (proxying producer considerations) and their recognition of the price-lowering effect of international trade (proxying consumer considerations) on support for the TPP are largely mediated by perceptions of trade. Together the findings suggest a middle ground between the two sides of the self-interest debate.
Concession Stands: How Mining Investments Incite Protest in Africa
Authors: Christensen Darin
Published: October 2018

Foreign investment in Africa's mineral resources has increased dramatically. This paper addresses three questions raised by this trend: do commercial mining investments increase the likelihood of social or armed conflict? If so, when are these disputes most prevalent? And, finally, what mechanisms help explain these conflicts? I show, first, that mining has contrasting effects on social and armed conflict: while the probability of protests or riots increases (roughly doubling) after mining starts, there is no increase in rebel activity. Second, I show that the probability of social conflict rises with plausibly exogenous increases in world commodity prices. Finally, I compile additional geo-spatial and survey data to explore potential mechanisms, including reporting bias, environmental harm, in-migration, inequality, and governance. Finding little evidence consistent with these accounts, I develop an explanation related to incomplete information—a common cause of conflict in industrial and international relations. This mechanism rationalizes why mining induces protest, why these conflicts are exacerbated by rising prices, and why transparency dampens the relationship between prices and protest.
Teaching English as a foreign language to primary school students in East Asia
Authors: Rao Zhenhui , Yu Ping
Published: October 2018

With the spread of economic globalization and the accelerating demand for English, governments in East Asian countries have been updating their English-in-education policies so as to enhance the quality of English education in the region (Hu & McKay, 2012). Of all these policies, the introduction of English as a compulsory subject at younger and younger ages is ‘possibly the world's biggest policy development in education’ (Johnstone, 2009: 33). It is widely believed that those who start learning English at an earlier age can utilize their ‘critical period’ to learn English more efficiently (Nunan, 2003; Y. Hu, 2007). However, the expansion of teaching English to young learners has not been unanimously supported and there is no conclusive evidence for the benefits of early exposure to a new language (Copland, Garton & Burns, 2014). Some researchers point out ‘the advantages of postponing formal teaching in specific contexts’ (Hyltenstam & Abrahamsson, 2001: 163).
Short-Term Effects on Diversity and Biomass on Grasslands from Artificial Dykes under Grazing and Mowing Treatments
Authors: Moinardeau Cannelle , Mesléard François , Ramone Hervé , Dutoit Thierry
Published: October 2018

Few studies document the impacts of conservation management practices such as extensive grazing or mowing on the new ecosystems created by industrial conversions. In southern France, the Rhône channelling led to the construction of dykes to protect the Tricastin industrialized area from floods. Aiming to control plant dynamics for safety reasons and to favour plant biodiversity, mowing or extensive grazing by cattle were recently tested. Monitoring from both permanent plots and aerial photographs shows that three years of extensive grazing and annual mechanical mowing have modified plant composition, significantly increasing plant species richness, evenness and heterogeneity. The increase in evenness and beta-diversity from grazing was significantly higher than from mowing. Only grazing was able to reduce the height and cover of the dominant tussock perennial grass species (Brachypodium phoenicoides), while increasing bare soil cover and thus the contribution of annual species. The Normalized Difference Vegetation Index (NDVI) obtained through aerial photographic analyses confirmed the correlation between NDVI, aboveground biomass and plant species richness for the grazed site alone, allowing the results obtained from quadrats to be generalized to the scale of the grazed site. On the Rhône’s artificial dykes, extensive grazing appears to be a better management tool than mowing to enhance plant biodiversity and meet safety objectives.
The effects of Trolox on the quality of sperm from captive squirrel monkey during liquefaction in the extender ACP-118™
Authors: Almeida D. V. C. , Lima J. S. , Leão D. L. , Oliveira K. G. , Santos R. R. , Domingues S. F. S. , Miranda M. S.
Published: October 2018

The aim of this study was to evaluate the effect of incubating semen for different periods (90, 270 or 450 min) with or without Trolox® (100 or 150 µM) on the quality of sperm from Saimiri collinsi. Sperm motility, vigour, and plasma membrane integrity (PMI) were evaluated in both fresh semen and semen incubated for different time periods, i.e. 90, 270 or 450 min of incubation. Supplementation of semen extender with Trolox® 100 µM improved sperm motility, vigour and PMI for up to 270 min of incubation.
Self-Perception of Theoretical Knowledge and Practical Skills by Primary Health Care Physicians in Life-Threatening Emergencies
Authors: Cernuda Martínez José Antonio , Castro Delgado Rafael , Ferrero Fernández Elena , Arcos González Pedro
Published: October 2018

Objectives

The goal of this study was to find out the training received in Urgent and Emergency Medicine (UEM) by the Primary Health Care (PHC) physicians of Asturias (Spain), as well as their perception of their own theoretical knowledge and practical skills in a series of procedures employed in life-threatening emergencies (LTEs), and also to analyze the differences according to the geographical area of their work.

Methods

This was a cross-sectional survey of PHC physicians using an ad hoc survey of a sample of 213 physicians in Asturias regarding their self-perception of theoretical knowledge and practical skills in techniques used in LTEs by areas of work (rural, suburban, and urban). The interview was conducted by mail from April through May 2017. The data processing has used absolute and relative frequencies, as well as central tendency parameters and dispersion parameters. The estimates for the entire population have been made using confidence intervals for the mean of 95%. In the comparison of parameters, the differences between parameters with a probability of error less than five percent (P<.05) have been considered significant. For the comparison of means between the different techniques in the different areas of work, ANOVA was used.

Results

With respect to the training of physicians, in general, for managing emergencies, both at the regional level and by areas of work (rural, suburban, and urban), none of the sets analyzed attained five points. By areas of work, it was the suburban region where there was a greater average general level of knowledge. There were significant differences in the average theoretical knowledge and the average practical skills in the procedures studied according to the different areas of work. The greater number of significant differences was between the urban and suburban regions and within the urban area.

Conclusions:

It’s necessary to ensure an adequate homogeneity of the levels of theoretical knowledge and practical skills of PHC physicians in order to guarantee the equity of provision of health care in emergencies in different geographical areas.

Cernuda MartínezJA, Castro DelgadoR, Ferrero FernándezE, Arcos GonzálezP. Self-perception of theoretical knowledges and practical skills by primary health care physicians in life-threatening emergencies. Prehosp Disaster Med. 2018;33(5):508–518.
Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24 Months in Empirically Derived Subtypes of Mild Cognitive Impairment
Authors: Edmonds Emily C. , Weigand Alexandra J. , Thomas Kelsey R. , Eppig Joel , Delano-Wood Lisa , Galasko Douglas R. , Salmon David P. , Bondi Mark W.
Published: October 2018

Objectives: Although subjective cognitive complaints (SCC) are an integral component of the diagnostic criteria for mild cognitive impairment (MCI), previous findings indicate they may not accurately reflect cognitive ability. Within the Alzheimer’s Disease Neuroimaging Initiative, we investigated longitudinal change in the discrepancy between self- and informant-reported SCC across empirically derived subtypes of MCI and normal control (NC) participants. Methods: Data were obtained for 353 MCI participants and 122 “robust” NC participants. Participants were classified into three subtypes at baseline via cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a presumptive false-positive group who performed within normal limits on neuropsychological testing. SCC at baseline and two annual follow-up visits were assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores between self- and informant-report were calculated. Analysis of change was conducted using analysis of covariance. Results: The amnestic and mixed MCI subtypes demonstrated increasing ECog discrepancy scores over time. This was driven by an increase in informant-reported SCC, which corresponded to participants’ objective cognitive decline, despite stable self-reported SCC. Increasing unawareness was associated with cerebrospinal fluid Alzheimer’s disease biomarker positivity and progression to Alzheimer’s disease. In contrast, CDN and NC groups over-reported cognitive difficulty and demonstrated normal cognition at all time points. Conclusions: MCI participants’ discrepancy scores indicate progressive underappreciation of their evolving cognitive deficits. Consistent over-reporting in the CDN and NC groups despite normal objective cognition suggests that self-reported SCC do not predict impending cognitive decline. Results demonstrate that self-reported SCC become increasingly misleading as objective cognitive impairment becomes more pronounced. (JINS, 2018, 24, 842–853)
Extent of implementation of food environment policies by the Malaysian Government: gaps and priority recommendations
Authors: Ng SeeHoe , Swinburn Boyd , Kelly Bridget , Vandevijvere Stefanie , Yeatman Heather , Ismail Mohd Noor , Karupaiah Tilakavati
Published: October 2018

Objective

To determine the degree of food environment policies that have been implemented and supported by the Malaysian Government, in comparison to international best practice, and to establish prioritised recommendations for the government based on the identified implementation gaps.

Design

The Healthy Food-Environment Policy Index (Food-EPI) comprises forty-seven indicators of government policy practice. Local evidence of each indicator was compiled from government institutions and verified by related government stakeholders. The extent of implementation of the policies was rated by experts against international best practices. Rating results were used to identify and propose policy actions which were subsequently prioritised by the experts based on ‘importance’ and ‘achievability’ criteria. The policy actions with relatively higher ‘achievability’ and ‘importance’ were set as priority recommendations for government action.

Setting

Malaysia.

Subjects

Twenty-six local experts.

Results

Majority (62 %) of indicators was rated ‘low’ implementation with no indicator rated as either ‘high’ or ‘very little, if any’ in terms of implementation. The top five recommendations were (i) restrict unhealthy food marketing in children’s settings and (ii) on broadcast media; (iii) mandatory nutrition labelling for added sugars; (iv) designation of priority research areas related to obesity prevention and diet-related non-communicable diseases; and (v) introduce energy labelling on menu boards for fast-food outlets.

Conclusions

This first policy study conducted in Malaysia identified a number of gaps in implementation of key policies to promote healthy food environments, compared with international best practices. Study findings could strengthen civil society advocacies for government accountability to create a healthier food environment.
Secondary Electron Energy Contrast of Localized Buried Charge in Metal–Insulator–Silicon Structures
Authors: Srinivasan Avinash , Han Weiding , Khursheed Anjam
Published: October 2018

This paper presents a new method for creating and monitoring controlled localized negatively charged regions inside insulators with a scanning electron microscope (SEM). A localized buried charged region is created and observed close to the point where a high voltage primary beam (10 kV) strikes a metal–insulator–silicon specimen. The amount of buried charge within the insulator at any given moment can be dynamically monitored by detecting the appearance of a second peak in the secondary electron (SE) energy spectrum. SE energy spectral signals were obtained through the use of a compact high signal-to-noise energy analyzer attachment that was fitted on to the SEM specimen stage. An electrostatic model, together with Monte Carlo simulations, is presented to explain how the SE charge contrast effect functions. This model is then experimentally confirmed by using the SE energy spectral signal induced by a gallium ion beam inside a dual focused ion beam-SEM instrument.
Persistence and Movement of Fomesafen in Florida Strawberry Production
Authors: Reed Thomas V. , Boyd Nathan S. , Wilson P. Christopher , Dittmar Peter J. , Sharpe Shaun M.
Published: October 2018

Fomesafen is a protoporphyrinogen oxidase–inhibitor herbicide with an alternative mode of action that provides PRE weed control in strawberry [Fragaria×ananassa(Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] produced in a plasticulture setting in Florida. Plasticulture mulch could decrease fomesafen dissipation and increase crop injury in rotational crops. Field experiments were conducted in Balm, FL, to investigate fomesafen persistence and movement in soil in Florida strawberry systems for the 2014/2015 and 2015/2016 production cycles. Treatments included fomesafen preplant at 0, 0.42, and 0.84 kg ai ha−1. Soil samples were taken under the plastic from plots treated with fomesafen at 0.42 kg ha−1throughout the production cycle. Fomesafen did not injure strawberry or decrease yield. Fomesafen concentration data for the 0.0- to 0.1-m soil depth were described using a three-parameter logistic function. The fomesafen 50% dissipation times were 37 and 47 d for the 2014/2015 and 2015/2016 production cycles, respectively. At the end of the study, fomesafen was last detected in the 0.0- to 0.1-m depth soil at 167 and 194 d after treatment in the 2014/2015 and 2015/2016 production cycles, respectively. Fomesafen concentration was less than 25 ppb on any sampling date for 0.1- to 0.2-m and 0.2- to 0.3-m depths. Fomesafen concentration decreased significantly after strawberry was transplanted and likely leached during overhead and drip irrigation used during the crop establishment.
Insights on Upper Mantle Melting, Rheology, and Anelastic Behavior From Seismic Shear Wave Tomography
Authors: Cobden Laura , Trampert Jeannot , Fichtner Andreas
Published: October 2018

In seismic tomography we map the wave speed structure inside the Earth, but we ultimately seek to interpret those images in terms of physical parameters. This is challenging because many parameters can trade‐off with each other to produce a given wave speed. The problem is compounded by the convention of mapping seismic structures as perturbations relative to a 1‐D reference model, rather than absolute wave speeds. Using a full waveform tomography model of Europe as a case study, we quantify the extent to which thermochemical and dynamic properties can be constrained using only S wave speed, expressed in absolute values. The wave speed distributions of this tomography model are compared with 4 million thermochemical models, whose seismic properties are computed via thermodynamic modeling. These models sample the full range of realistic mantle compositions, including variable water and melt contents, and mineral intrinsic anelasticity is taken into account. Intrinsic anelasticity causes waves to travel more slowly at higher temperatures, leading to seismic attenuation, but the sensitivity of the wave speed reduction to temperature is, in turn, controlled by the wave frequency. Global studies of surface waves indicate an anticorrelation between S wave speed and attenuation. We therefore only retain thermochemical models satisfying this anticorrelation. Our study indicates that the frequency dependence of anelasticity, α, depends on temperature or rheology, with α ≈ 0.1 being most appropriate in cold or lithospheric mantle and α ≈ 0.3 in warmer regions (i.e., the asthenosphere). Additionally, the slowest regions require specific compositions and/or a velocity‐weakening mechanism, such as partial melting, elastically accommodated grain boundary sliding, or water.
Shear Flow Instabilities and Unstable Events Over the North Bay of Bengal
Authors: Jampana Venkata , Ravichandran M. , Sengupta Debasis , D'Asaro E. A. , Rahaman Hasibur , Joseph Sudheer , Sreelekha J. , Chaudhuri Dipanjan
Published: October 2018

A year‐long mooring data are used to study the upper ocean unstable events and instabilities at 18°N 89°E, which is a climatologically important region in the North Bay of Bengal. Near‐surface stability is studied from the context of the buoyancy frequency normalized shear (Vz/N) and reduced shear (S2−4N2) which are convenient measures to quantify flow stability, compared to the more widely used Richardson number (Ri). The analysis is carried out across three contrasting time periods, the monsoon, postmonsoon, and the winter of year 2012. Although it is well known that the flow stability changes from stable to unstable at Ri = Ricr=0.25, the relative importance of the perturbations of shear and buoyancy frequency in driving the unstable events is not well studied over the open oceans and more particularly over the Bay of Bengal. At 18°N, 89°E both higher than average shear and lower than average buoyancy frequency perturbations are crucial in driving the unstable events during the summer and premonsoon period. However, at increasing depths, the influence of shear perturbations becomes more dominant. Invoking the Miles‐Howard criteria for flow instability, it is seen that during the postmonsoon period, the buoyancy frequency perturbations are more critical than shear perturbations in driving the unstable events. In winter, the unstable events are influenced by both the buoyancy frequency and shear perturbations.
The Density‐Driven Winter Intensification of the Ross Sea Circulation
Authors: Jendersie Stefan , Williams Michael J. M. , Langhorne Pat J. , Robertson Robin
Published: October 2018

The circulation over the Ross Sea continental shelf facilitates the exchange between the Southern Ocean and the Ross Ice Shelf cavity. Here transport and mixing processes control the access of oceanic heat from the Southern Ocean to the ice shelf base, the formation of sea ice, and the production of High Salinity Shelf Water (HSSW) in polynyas and hence the subsequent formation of Antarctic Bottom Water. A climatological ocean‐ice shelf coupled model of the Ross Sea Sector including the cavity, with prescribed sea ice fluxes, was used to examine the details of currents and their seasonal variability over the continental shelf. A system of two cyclonic and three anticyclonic persistent circulation features has been identified. Transports steadily increase throughout winter, with individual currents carrying up to 2 Sv, nearly doubling their minimum. The seasonal modulation is driven by lateral differences in density and subsequent baroclinic pressure gradients, induced through dense shelf water formation in the Ross Sea and the Terra Nova Bay Polynas. Wind plays a minor role in ocean momentum variability. Sensitivity experiments suggest a weakening of transports with increasing wind stress. Horizontal density variations at the ocean surface are smoothed by the wind. The source of momentum in the cavity is the gravity‐driven bottom flow of HSSW, produced in the Ross Sea Polynya as part of the thermohaline overturning circulation. Tracer experiments suggest that HSSW forming in the Terra Nova Bay Polynya has no cavity access, but instead is the main contributor to Antarctic Bottom Water formed in the northwest slope.
New Definition of Potential Spicity by the Least Square Method
Authors: Huang Rui Xin , Yu Lu‐Sha , Zhou Sheng‐Qi
Published: October 2018

A differentiable function whose contours are orthogonal to potential density (σ) contours does not exist. However, such a function, called potential spicity (π), can be defined in the least square sense; these two functions form a practically orthogonal coordinate system in potential temperature‐salinity (θ‐S) space. Thus, in addition to the classical potential temperature‐salinity (θ‐S) diagram, seawater properties can be studied in the potential density‐potential spicity (σ − π) diagram.
Modeling the Midlatitude Ionosphere Storm‐Enhanced Density Distribution With a Data Assimilation Model
Authors: Gardner L. C. , Schunk R. W. , Scherliess L. , Eccles V. , Basu S. , Valladeres C.
Published: October 2018

The Utah State University Global Assimilation of Ionospheric Measurements‐Gauss Markov model has been used to investigate the distribution of ionospheric plasma during storm times over the continental United States. Storm periods dramatically increase the effects of space weather on the ionosphere and upper atmosphere, leading to impacts on over‐the‐horizon radars, Global Positioning System location determination, spacecraft charging, power grid overloads, and disruption of the Federal Aviation Administration Wide Area Augmentation System to name a few. Four storm periods were investigated where strong storm‐enhanced densities (SEDs) were present: two strong, October 2003 and November 2003, and two moderate, August 2010 and August 2011. It was found that a fundamental difference in the SED formation exists between the strong and moderate storms. For the strong storms, the SED was formed from the plasma in the northern equatorial anomaly crest, with the plasma in the SED channel lifting the closer it came to the high latitudes. For the moderate storms, the SED appeared to be unconnected to the northern anomaly crest but was rather produced locally in the SED channel, along with no corresponding increase in layer height associated with the SED evident in the model.
Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer
Authors: Chen Feng , Ma Kai , Madajewski Brian , Zhuang Li , Zhang Li , Rickert Keith , Marelli Marcello , Yoo Barney , Turker Melik Z. , Overholtzer Michael , Quinn Thomas P. , Gonen Mithat , Zanzonico Pat , Tuesca Anthony , Bowen Michael A. , Norton Larry , Subramony J. Anand , Wiesner Ulrich , Bradbury Michelle S.
Published: October 2018

Controlling the biodistribution of nanoparticles upon intravenous injection is the key to achieving target specificity. One of the impediments in nanoparticle-based tumor targeting is the inability to limit the trafficking of nanoparticles to liver and other organs leading to smaller accumulated amounts in tumor tissues, particularly via passive targeting. Here we overcome both these challenges by designing nanoparticles that combine the specificity of antibodies with favorable particle biodistribution profiles, while not exceeding the threshold for renal filtration as a combined vehicle. To that end, ultrasmall silica nanoparticles are functionalized with anti-human epidermal growth factor receptor 2 (HER2) single-chain variable fragments to exhibit high tumor-targeting efficiency and efficient renal clearance. This ultrasmall targeted nanotheranostics/nanotherapeutic platform has broad utility, both for imaging a variety of tumor tissues by suitably adopting the targeting fragment and as a potentially useful drug delivery vehicle.
A global strategy to mitigate the environmental impact of China’s ruminant consumption boom
Authors: Du Yuanyuan , Ge Ying , Ren Yuan , Fan Xing , Pan Kaixuan , Lin Linshan , Wu Xu , Min Yong , Meyerson Laura A. , Heino Mikko , Chang Scott X. , Liu Xiaozi , Mao Feng , Yang Guofu , Peng Changhui , Qu Zelong , Chang Jie , Didham Raphael K.
Published: October 2018

Rising demand for ruminant meat and dairy products in developing countries is expected to double anthropogenic greenhouse gas and ammonia emissions from livestock by 2050. Mitigation strategies are urgently needed to meet demand while minimizing environmental impacts. Here, we develop scenarios for mitigating emissions under local vs global supply policies using data from 308 livestock farms across mainland China, where emissions intensities are ~50% higher than those in developed nations. Intensification of domestic production and globalized expansion through increased trade result in reductions in global emissions by nearly 30% over a business-as-usual scenario, but at the expense of trading partners absorbing the associated negative externalities of environmental degradation. Only adoption of a mixed strategy combining global best-practice in sustainable intensification of domestic production, with increased green-source trading as a short-term coping strategy, can meet 2050 demand while minimizing the local and global environmental footprint of China’s ruminant consumption boom.
Dopamine–endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum
Authors: Xu Hao , Perez Sylvie , Cornil Amandine , Detraux Bérangère , Prokin Ilya , Cui Yihui , Degos Bertrand , Berry Hugues , de Kerchove d’Exaerde Alban , Venance Laurent
Published: October 2018

Dopamine modulates striatal synaptic plasticity, a key substrate for action selection and procedural learning. Thus, characterizing the repertoire of activity-dependent plasticity in striatum and its dependence on dopamine is of crucial importance. We recently unraveled a striatal spike-timing-dependent long-term potentiation (tLTP) mediated by endocannabinoids (eCBs) and induced with few spikes (~5–15). Whether this eCB-tLTP interacts with the dopaminergic system remains to be investigated. Here, we report that eCB-tLTP is impaired in a rodent model of Parkinson’s disease and rescued by L-DOPA. Dopamine controls eCB-tLTP via dopamine type-2 receptors (D2R) located presynaptically in cortical terminals. Dopamine–endocannabinoid interactions via D2R are required for the emergence of tLTP in response to few coincident pre- and post-synaptic spikes and control eCB-plasticity by modulating the long-term potentiation (LTP)/depression (LTD) thresholds. While usually considered as a depressing synaptic function, our results show that eCBs in the presence of dopamine constitute a versatile system underlying bidirectional plasticity implicated in basal ganglia pathophysiology.
Simple ruthenium-catalyzed reductive amination enables the synthesis of a broad range of primary amines
Authors: Senthamarai Thirusangumurugan , Murugesan Kathiravan , Schneidewind Jacob , Kalevaru Narayana V. , Baumann Wolfgang , Neumann Helfried , Kamer Paul C. J. , Beller Matthias , Jagadeesh Rajenahally V.
Published: October 2018

The production of primary benzylic and aliphatic amines, which represent essential feedstocks and key intermediates for valuable chemicals, life science molecules and materials, is of central importance. Here, we report the synthesis of this class of amines starting from carbonyl compounds and ammonia by Ru-catalyzed reductive amination using H2. Key to success for this synthesis is the use of a simple RuCl2(PPh3)3 catalyst that empowers the synthesis of >90 various linear and branched benzylic, heterocyclic, and aliphatic amines under industrially viable and scalable conditions. Applying this catalyst, −NH2 moiety has been introduced in functionalized and structurally diverse compounds, steroid derivatives and pharmaceuticals. Noteworthy, the synthetic utility of this Ru-catalyzed amination protocol has been demonstrated by upscaling the reactions up to 10 gram-scale syntheses. Furthermore, in situ NMR studies were performed for the identification of active catalytic species. Based on these studies a mechanism for Ru-catalyzed reductive amination is proposed.
Pressure tuning of charge ordering in iron oxide
Authors: Ovsyannikov Sergey V. , Bykov Maxim , Bykova Elena , Glazyrin Konstantin , Manna Rudra Sekhar , Tsirlin Alexander A. , Cerantola Valerio , Kupenko Ilya , Kurnosov Alexander V. , Kantor Innokenty , Pakhomova Anna S. , Chuvashova Irina , Chumakov Aleksandr I. , Rüffer Rudolf , McCammon Catherine , Dubrovinsky Leonid S.
Published: October 2018

A Verwey-type charge-ordering transition in magnetite at 120 K leads to the formation of linear units of three iron ions with one shared electron, called trimerons. The recently-discovered iron pentoxide (Fe4O5) comprising mixed-valent iron cations at octahedral chains, demonstrates another unusual charge-ordering transition at 150 K involving competing formation of iron trimerons and dimerons. Here, we experimentally show that applied pressure can tune the charge-ordering pattern in Fe4O5 and strongly affect the ordering temperature. We report two charge-ordered phases, the first of which may comprise both dimeron and trimeron units, whereas, the second exhibits an overall dimerization involving both the octahedral and trigonal-prismatic chains of iron in the crystal structure. We link the dramatic change in the charge-ordering pattern in the second phase to redistribution of electrons between the octahedral and prismatic iron chains, and propose that the average oxidation state of the iron cations can pre-determine a charge-ordering pattern.
Formation of the β-barrel assembly machinery complex in lipid bilayers as seen by solid-state NMR
Authors: Pinto Cecilia , Mance Deni , Sinnige Tessa , Daniëls Mark , Weingarth Markus , Baldus Marc
Published: October 2018

The β-barrel assembly machinery (BAM) is a pentameric complex (BamA–E), which catalyzes the essential process of β-barrel protein insertion into the outer membrane of E. coli. Thus far, a detailed understanding of the insertion mechanism has been elusive but recent results suggest that local protein motion, in addition to the surrounding membrane environment, may be of critical relevance. We have devised a high-sensitivity solid-state NMR approach to directly probe protein motion and the structural changes associated with BAM complex assembly in lipid bilayers. Our results reveal how essential BamA domains, such as the interface formed by the polypeptide transport associated domains P4 and P5 become stabilized after complex formation and suggest that BamA β-barrel opening and P5 reorientation is directly related to complex formation in membranes. Both the lateral gate, as well as P5, exhibit local dynamics, a property that could play an integral role in substrate recognition and insertion.
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup
Authors: Chan Chang S. , Laddha Saurabh V. , Lewis Peter W. , Koletsky Matthew S. , Robzyk Kenneth , Da Silva Edaise , Torres Paula J. , Untch Brian R. , Li Janet , Bose Promita , Chan Timothy A. , Klimstra David S. , Allis C. David , Tang Laura H.
Published: October 2018

The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha-cells (FDR q-value < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.
Deletions linked to PROG1 gene participate in plant architecture domestication in Asian and African rice
Authors: Wu Yongzhen , Zhao Shuangshuang , Li Xianran , Zhang Bosen , Jiang Liyun , Tang Yanyan , Zhao Jie , Ma Xin , Cai Hongwei , Sun Chuanqing , Tan Lubin
Published: October 2018

Improving the yield by modifying plant architecture was a key step during crop domestication. Here, we show that a 110-kb deletion on the short arm of chromosome 7 in Asian cultivated rice (Oryza sativa), which is closely linked to the previously identified PROSTRATE GROWTH 1 (PROG1) gene, harbors a tandem repeat of seven zinc-finger genes. Three of these genes regulate the plant architecture, suggesting that the deletion also promoted the critical transition from the prostrate growth and low yield of wild rice (O. rufipogon) to the erect growth and high yield of Asian cultivated rice. We refer to this locus as RICE PLANT ARCHITECTURE DOMESTICATION (RPAD). Further, a similar but independent 113-kb deletion is detected at the RPAD locus in African cultivated rice. These results indicate that the deletions, eliminating a tandem repeat of zinc-finger genes, may have been involved in the parallel domestication of plant architecture in Asian and African rice.
Time units for learning involving maintenance of system-wide cFos expression in neuronal assemblies
Authors: Chowdhury Ananya , Caroni Pico
Published: October 2018

Repeated experiences may be integrated in succession during a learning process, or they may be combined as a whole within dedicated time windows to possibly promote quality control. Here we show that in Pavlovian, incremental and incidental learning, related information acquired within time windows of 5 h is combined to determine what mice learn. Trials required for learning had to occur within 5 h, when learning-related shared cues could produce association and interference. Upon acquisition, cFos expression was elevated during 5 h throughout specific system-wide neuronal assemblies. Time window function depended on network activity and cFos expression. Local cFos activity was required for distant assembly recruitment through network activity and distant BDNF. Activation of learning-related cFos assemblies was sufficient and necessary for time window function. Therefore, learning processes consist of dedicated 5 h time windows (time units for learning), involving maintenance of system-wide neuronal assemblies through network activity and cFos expression.
ATR/Chk1 signaling induces autophagy through sumoylated RhoB-mediated lysosomal translocation of TSC2 after DNA damage
Authors: Liu Mingdong , Zeng Taoling , Zhang Xin , Liu Chunyan , Wu Zhihui , Yao Luming , Xie Changchuan , Xia Hui , Lin Qi , Xie Liping , Zhou Dawang , Deng Xianming , Chan Hong-Lin , Zhao Tong-Jin , Wang Hong-Rui
Published: October 2018

DNA damage can induce autophagy; however, the underlying mechanism remains largely unknown. Here we report that DNA damage leads to autophagy through ATR/Chk1/RhoB-mediated lysosomal recruitment of TSC complex and subsequent mTORC1 inhibition. DNA damage caused by ultraviolet light (UV) or alkylating agent methyl methanesulphonate (MMS) results in phosphorylation of small GTPase RhoB by Chk1. Phosphorylation of RhoB enhances its interaction with the TSC2, and promotes its sumoylation by PIAS1, which is required for RhoB/TSC complex to translocate to lysosomes. As a result, mTORC1 is inhibited, and autophagy is activated. Knockout of RhoB severely attenuates lysosomal translocation of TSC complex and the DNA damage-induced autophagy. Reintroducing wild-type but not sumoylation-resistant RhoB into RhoB−/− cells restores the onset of autophagy. Hence, our study identifies a molecular mechanism for translocation of TSC complex to lysosomes in response to DNA damage, which depends on ATR/Chk1-mediated RhoB phosphorylation and sumoylation.
A comprehensive overview of genomic imprinting in breast and its deregulation in cancer
Authors: Goovaerts Tine , Steyaert Sandra , Vandenbussche Chari A. , Galle Jeroen , Thas Olivier , Van Criekinge Wim , De Meyer Tim
Published: October 2018

Genomic imprinting plays an important role in growth and development. Loss of imprinting (LOI) has been found in cancer, yet systematic studies are impeded by data-analytical challenges. We developed a methodology to detect monoallelically expressed loci without requiring genotyping data, and applied it on The Cancer Genome Atlas (TCGA, discovery) and Genotype-Tissue expression project (GTEx, validation) breast tissue RNA-seq data. Here, we report the identification of 30 putatively imprinted genes in breast. In breast cancer (TCGA),HM13is featured by LOI and expression upregulation, which is linked to DNA demethylation. Other imprinted genes typically demonstrate lower expression in cancer, often associated with copy number variation and aberrant DNA methylation. Downregulation in cancer frequently leads to higher relative expression of the (imperfectly) silenced allele, yet this is not considered canonical LOI given the lack of (absolute) re-expression. In summary, our novel methodology highlights the massive deregulation of imprinting in breast cancer.
Subtomogram averaging of COPII assemblies reveals how coat organization dictates membrane shape
Authors: Hutchings Joshua , Stancheva Viktoriya , Miller Elizabeth A. , Zanetti Giulia
Published: October 2018

Eukaryotic cells employ membrane-bound carriers to transport cargo between compartments in a process essential to cell functionality. Carriers are generated by coat complexes that couple cargo capture to membrane deformation. The COPII coat mediates export from the endoplasmic reticulum by assembling in inner and outer layers, yielding carriers of variable shape and size that allow secretion of thousands of diverse cargo. Despite detailed understanding of COPII subunits, the molecular mechanisms of coat assembly and membrane deformation are unclear. Here we present a 4.9 Å cryo-tomography subtomogram averaging structure of in vitro-reconstituted membrane-bound inner coat. We show that the outer coat (Sec13–Sec31) bridges inner coat subunits (Sar1–Sec23–Sec24), promoting their assembly into a tight lattice. We directly visualize the membrane-embedded Sar1 amphipathic helix, revealing that lattice formation induces parallel helix insertions, yielding tubular curvature. We propose that regulators like the procollagen receptor TANGO1 modulate this mechanism to determine vesicle shape and size.
Blood meal-induced inhibition of vector-borne disease by transgenic microbiota
Authors: Shane Jackie L. , Grogan Christina L. , Cwalina Caroline , Lampe David J.
Published: October 2018

Vector-borne diseases are a substantial portion of the global disease burden; one of the deadliest of these is malaria. Vector control strategies have been hindered by mosquito and pathogen resistances, and population alteration approaches using transgenic mosquitos still have many hurdles to overcome before they can be implemented in the field. Here we report a paratransgenic control strategy in which the microbiota of Anopheles stephensi was engineered to produce an antiplasmodial effector causing the mosquito to become refractory to Plasmodium berghei. The midgut symbiont Asaia was used to conditionally express the antiplasmodial protein scorpine only when a blood meal was present. These blood meal inducible Asaia strains significantly inhibit pathogen infection, and display improved fitness compared to strains that constitutively express the antiplasmodial effector. This strategy may allow the antiplasmodial bacterial strains to survive and be transmitted through mosquito populations, creating an easily implemented and enduring vector control strategy.
ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
Authors: Teng Yaqun , Yadav Tribhuwan , Duan Meihan , Tan Jun , Xiang Yufei , Gao Boya , Xu Jianquan , Liang Zhuobin , Liu Yang , Nakajima Satoshi , Shi Yi , Levine Arthur S. , Zou Lee , Lan Li
Published: October 2018

Actively transcribed regions of the genome are protected by transcription-coupled DNA repair mechanisms, including transcription-coupled homologous recombination (TC-HR). Here we used reactive oxygen species (ROS) to induce and characterize TC-HR at a transcribed locus in human cells. As canonical HR, TC-HR requires RAD51. However, the localization of RAD51 to damage sites during TC-HR does not require BRCA1 and BRCA2, but relies on RAD52 and Cockayne Syndrome Protein B (CSB). During TC-HR, RAD52 is recruited by CSB through an acidic domain. CSB in turn is recruited by R loops, which are strongly induced by ROS in transcribed regions. Notably, CSB displays a strong affinity for DNA:RNA hybrids in vitro, suggesting that it is a sensor of ROS-induced R loops. Thus, TC-HR is triggered by R loops, initiated by CSB, and carried out by the CSB-RAD52-RAD51 axis, establishing a BRCA1/2-independent alternative HR pathway protecting the transcribed genome.
Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism
Authors: Peek James , Lilic Mirjana , Montiel Daniel , Milshteyn Aleksandr , Woodworth Ian , Biggins John B. , Ternei Melinda A. , Calle Paula Y. , Danziger Michael , Warrier Thulasi , Saito Kohta , Braffman Nathaniel , Fay Allison , Glickman Michael S. , Darst Seth A. , Campbell Elizabeth A. , Brady Sean F.
Published: October 2018

Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these compounds is threatened by the increasing incidence of resistance (RifR). As resistance mechanisms found in clinical settings may also occur in natural environments, here we postulated that bacteria could have evolved to produce rifamycin congeners active against clinically relevant resistance phenotypes. We survey soil metagenomes and identify a tailoring enzyme-rich family of gene clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with potent in vivo and in vitro activity against the most common clinically relevant RifR mutations. Our structural and mechanistic analyses reveal the basis for Kang inhibition of RifR RNAP. Unlike Rifs, Kangs function through a mechanism that includes interfering with 5′-initiating substrate binding. Our results suggest that examining soil microbiomes for new analogues of clinically used antibiotics may uncover metabolites capable of circumventing clinically important resistance mechanisms.
Fractionalized excitations in the partially magnetized spin liquid candidate YbMgGaO4
Authors: Shen Yao , Li Yao-Dong , Walker H. C. , Steffens P. , Boehm M. , Zhang Xiaowen , Shen Shoudong , Wo Hongliang , Chen Gang , Zhao Jun
Published: October 2018

Quantum spin liquids (QSLs) are exotic states of matter characterized by emergent gauge structures and fractionalized elementary excitations. The recently discovered triangular lattice antiferromagnet YbMgGaO4 is a promising QSL candidate, and the nature of its ground state is still under debate. Here we use neutron scattering to study the spin excitations in YbMgGaO4 under various magnetic fields. Our data reveal a dispersive spin excitation continuum with clear upper and lower excitation edges under a weak magnetic field (H = 2.5 T). Moreover, a spectral crossing emerges at the Γ point at the Zeeman-split energy. The corresponding redistribution of the spectral weight and its field-dependent evolution are consistent with the theoretical prediction based on the inter-band and intra-band spinon particle-hole excitations associated with the Zeeman-split spinon bands, implying the presence of fractionalized excitations and spinon Fermi surfaces in the partially magnetized QSL state in YbMgGaO4.
Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice
Authors: Kroeger Daniel , Absi Gianna , Gagliardi Celia , Bandaru Sathyajit S. , Madara Joseph C. , Ferrari Loris L. , Arrigoni Elda , Münzberg Heike , Scammell Thomas E. , Saper Clifford B. , Vetrivelan Ramalingam
Published: October 2018

The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POAGAL neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPOGAL neurons in mice promotes sleep with low frequency stimulation (1–4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPOGAL neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPOGAL neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPOGAL neurons in both sleep induction and heat loss.