bluuebunny/crossref_metadata_2025 huggingface dataset:
The tectonic setting of the eastern margin of the Sino-Korean Block inferred from detrital zircon U–Pb age and Nd isotope composition of the Pyeongan Supergroup (upper Palaeozoic – Lower Triassic), Korea
Authors: KIM MUN GI , LEE YONG IL , CHOI TAEJIN , ORIHASHI YUJI
Published: November 2017

The upper Palaeozoic succession (Pyeongan Supergroup) in central eastern Korea is well correlated with the equivalent successions distributed in North China, suggestive of the Korean upper Palaeozoic being part of the Sino-Korean Block. Detrital zircon U–Pb ages and Sm–Nd isotope compositions of the Pyeongan Supergroup in the Samcheok coalfield of the Taebaeksan Basin were analysed. A single predominant zircon age peak atc. 1.9 Ga (> 70%) is marked in all sedimentary units, followed by varying amounts of minor late Palaeozoic grains (up to 30%). The rarity of Meso- to Neoproterozoic- and Silurian-aged zircons confirms that sediment influx from the South China and Qinling blocks was insignificant. The 2.0–1.8 Ga-dominated zircon age pattern and the Nd isotope composition (average εNd(0) = −15.5±4.0) of the Pyeongan Supergroup most closely reflect the signature of the Yeongnam Massif basements, which supports a previous hypothesis that the Pyeongan Supergroup was mostly derived from a palaeo-orogen located to the east–southeast. Relatively higher εNd(0) values (> −10.1) in the lowermost and the upper parts of the succession are closely matched by the increased occurrence of syn-depositional-aged zircons, which indicates considerable mixing of juvenile materials atc. 320 Ma and 260 Ma. Both arc-related magmatic events are interpreted to have been related to oceanic subduction, suggesting that the eastern margin of the Sino-Korean Block was an active continental margin during late Palaeozoic times.
The Domestic Politics of International Cooperation: Germany and the European Debt Crisis
Authors: Schneider Christina J. , Slantchev Branislav L.
Published: November 2017

International cooperation can fail even though governments have no distributional conflicts or incentives to free-ride, face no informational or credibility problems, and even agree on the policies that need to be implemented. Germany's refusal to cooperate with the Eurogroup members on the Greek bailout in 2010 until the crisis threatened to derail the entire Eurozone is puzzling in that regard especially because Germany is the main beneficiary of the euro. It was alleged at the time that this was a dilatory tactic designed to postpone a domestically unpopular decision until after crucial regional elections. But why would voters allow themselves to be misled like that? And why did Merkel agree to the bailout before the elections took place? To analyze how citizen preferences affect international cooperation, we develop a game-theoretic model of the four-way interaction between two governments that must coordinate a response to a crisis affecting both countries but who also must face the polls domestically with an electorate that might be uncertain whether a response is necessary. We find that, paradoxically, governments that stand to receive the greatest benefits from international cooperation face the greatest obstacles to implementing the required policies even when voters would want them to. We show how the model can rationalize Merkel's electoral strategy and why her party suffered at the polls when the strategy went off the rails.
Metabolomic analysis of alterations in lipid oxidation, carbohydrate and amino acid metabolism in dairy goats caused by exposure to Aflotoxin B1
Authors: Cheng Jianbo , Huang Shuai , Fan Caiyun , Zheng Nan , Zhang Yangdong , Li Songli , Wang Jiaqi
Published: November 2017

The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, β-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.
Effect of physical activity on cardiac autonomic function of dairy cows on commercial dairy farms
Authors: Kézér Fruzsina Luca , Tőzsér János , Bakony Mikolt , Szenci Ottó , Jurkovich Viktor , Kovács Levente
Published: November 2017

Interbeat interval data were collected from 219 Holstein cows in 2 smaller-scale farms and 3 larger-scale farms to investigate the effects of posture (standing vs. lying), rumination (rumination vs. no rumination) and feeding on baseline values of heart rate (HR) and heart rate variability (HRV) parameters reflecting vagal and sympathetic activity. A General Linear Model was used for detecting factors (parity, milking technology, herd size) having possible effects on HRV calculated for undisturbed lying posture. Basal values of cardiac parameters were also compared between larger and smaller-scale farms. Neither parity nor milking technology affected HRV parameters. Sympathetic activity increased in the order of lying, ruminating when lying, standing, ruminating when standing and feeding on both sizes of farms. Vagal activity decreased in that order in both lower- and larger-scale farms. Rumination caused an increase in HR and a decrease in vagal tone in both lower- and larger-scale farms and an increase in sympathetic activity during lying in both farm sizes. Basal vagal activity was lower in larger-scale farms compared to smaller-scale farms, while greater sympathetic activity was found in cows housed on larger-scale farms. Our findings demonstrate that reference values of HRV parameters in lactating dairy cows cannot be generally defined for Holstein cattle as they are affected by physical activity and herd size. Higher HR and sympathetic activity at rest in larger-scale farms compared to farms with lower cow population might be associated with higher levels of social stress and therefore should be considered as a potential welfare concern.
Rumination time as a potential predictor of common diseases in high-productive Holstein dairy cows
Authors: Moretti Riccardo , Biffani Stefano , Tiezzi Francesco , Maltecca Christian , Chessa Stefania , Bozzi Riccardo
Published: November 2017

We examined the hypothesis that rumination time (RT) could serve as a useful predictor of various common diseases of high producing dairy cows and hence improve herd management and animal wellbeing. We measured the changes in rumination time (RT) in the days before the recording of diseases (specifically: mastitis, reproductive system diseases, locomotor system issues, and gastroenteric diseases). We built predictive models to assess the association between RT and these diseases, using the former as the outcome variable, and to study the effects of the latter on the former. The average Pseudo-R2of the fitted models was moderate to low, and this could be due to the fact that RT is influenced by other additional factors which have a greater effect than the predictors used here. Although remaining in a moderate-to-low range, the average Pseudo-R2of the models regarding locomotion issues and gastroenteric diseases was higher than the others, suggesting the greater effect of these diseases on RT. The results are encouraging, but further work is needed if these models are to become useful predictors.
Significant changes in ITIH4, AHSG, ORM1, and CD46 content in milk fat globule membrane proteins of ketotic dairy cows
Authors: Gao Sansi , Yang Wei , Yu Hongjiang , Liu Runqi , Dong Zhihao , Zhang Hongyou , Xia Cheng , Xu Chuang
Published: November 2017

High concentrations of non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHBA) in cows’ blood caused by ketosis are associated with inflammatory states. We hypothesised that ketosis in postparturient dairy cows would result in altered levels on inflammation-related proteins not only in plasma but also in the milk fat globule membranes (MFGM). Thirty cows were selected from a dairy farm in Heilongjiang, China. Inflammatory milk fat globule membrane proteins were detected using ELISA kits, and a fully automatic biochemical analyser was used to measure the concentrations of BHBA, NEFA, glucose (GLU) and triglyceride (TG) in plasma. MFGM protein from milk of ketotic cows contained significantly different concentrations of acute-phase response proteins (complement C3 (C3), prothrombin (F2), alpha-1-acid glycoprotein (ORM1), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), alpha-2-HS-glycoprotein (AHSG), complement C9 (C9), complement regulatory protein variant 4 (CD46)) in comparison with milk from non-ketotic cows. Blood concentrations of C3, complement C9 (C9), tumour necrosis factor α (TNFα), MFGM C3, monocyte differentiation antigen CD14 (CD14) and ORM1 levels were correlated with energy balance. ITIH4 and CD46 increased, and AHSG and ORM1 decreased before the onset of ketosis. These biomarkers offer potential as predictors and monitors of ketosis in at-risk cows.
Therapeutic and protective effects of autologous serum in amikacin-induced ototoxicity
Authors: Arslan I B , Aslan G G , Mercan G C , Vatansever S , Cukurova I , Gokalp S , Aslan A
Published: November 2017

Objective:

Possible therapeutic and protective benefits of intratympanic autologous serum application in amikacin-induced ototoxicity were investigated.

Methods:

Twenty-four guinea pigs were separated equally into two groups: therapeutic (group A) and protective (group B). Transient evoked otoacoustic emissions were recorded before and after autologous serum application. Apoptotic cells were identified in the organ of Corti, spiral limbus and spiral ganglion by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (‘TUNEL’) method.

Results:

Transient evoked otoacoustic emission responses at 1, 1.4 and 2.8 kHz improved without significance after autologous serum application in group A (p> 0.05). A significantly protective effect of autologous serum was determined at 4 kHz in group B (p< 0.05). There were significantly fewer apoptotic cells at the spiral limbus in the therapeutic and protective groups compared to the control group (p< 0.05).

Conclusion:

Autologous serum may offer protection against ototoxicity-induced hearing loss, but it cannot restore hearing. Immunohistochemically, autologous serum significantly decreases activation of the intrinsic pathway of pro-apoptotic signalling in mesenchymal cells compared to neurons and neurosensory cells.
What can be learned about the enzyme ATPase from single-molecule studies of its subunit F1?
Authors: Volkán-Kacso Sándor , Marcus Rudolph A.
Published: November 2017

We summarize the different types of single molecule experiments on the F1component of FOF1-ATP Synthase and what has been learned from them. We also describe results from our recent studies on interpreting the experiments using a chemical-mechanical theory for these biological motors.
DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase
Authors: Taghavi Amirhossein , van der Schoot Paul , Berryman Joshua T.
Published: November 2017

Using atomistic simulations, we show the formation of stable triplet structure when particular GC-rich DNA duplexes are extended in solution over a timescale of hundreds of nanoseconds, in the presence of organic salt. We present planar-stacked triplet disproportionated DNA (Σ DNA) as a possible solution phase of the double helix under tension, subject to sequence and the presence of stabilising co-factors. Considering the partitioning of the duplexes into triplets of base pairs as the first step of operation of recombinase enzymes like RecA, we emphasise the structure–function relationship in Σ DNA. We supplement atomistic calculations with thermodynamic arguments to show that codons for ‘phase 1’ amino acids (those appearing early in evolution) are more likely than a lower entropy GC-rich sequence to form triplets under tension. We further observe that the four amino acids supposed (in the ‘GADV world’ hypothesis) to constitute the minimal set to produce functional globular proteins have the strongest triplet-forming propensity within the phase 1 set, showing a series of decreasing triplet propensity with evolutionary newness. The weak form of our observation provides a physical mechanism to minimise read frame and recombination alignment errors in the early evolution of the genetic code.
REFLECTIONS ON THE NICE DECISION TO REJECT PATIENT PRODUCTION LOSSES
Authors: Shearer James , Byford Sarah , Birch Steve
Published: November 2017

Objectives:Patient production losses occur when individuals’ capacities to work, whether paid or unpaid, are impaired by illness, treatment, disability, or death. There is controversy about whether and how to include patient production losses in economic evaluations in health care. Patient production losses have not previously been considered when evaluating medications for reimbursement under the U.K. National Health Service. Proposals for value-based assessment of health technologies in the United Kingdom created renewed interest in whether and how to include costs from a wider societal perspective, such as patient production losses, within economic evaluation of healthcare interventions.

Methods:A narrative review was undertaken of theoretical, ethical, and policy issues that might inform decisions that involve the normative question of whether or not to include patient production losses in economic evaluation.

Results:It seems difficult to reconcile the implications of including patient production losses with the objectives of a healthcare system dedicated to providing universal healthcare coverage without regard to patients’ ability to pay.

Conclusions:Tax payer funded healthcare systems may legitimately adopt maximands other than health gain, but these will be at the opportunity cost of less than maximum health gains.
Normalized solutions for nonlinear Schrödinger systems
Authors: Bartsch Thomas , Jeanjean Louis
Published: November 2017

We consider the existence of normalized solutions in H1(ℝN) × H1(ℝN) for systems of nonlinear Schr¨odinger equations, which appear in models for binary mixtures of ultracold quantum gases. Making a solitary wave ansatz, one is led to coupled systems of elliptic equations of the form

and we are looking for solutions satisfying

where a1> 0 and a2> 0 are prescribed. In the system, λ1 and λ2 are unknown and will appear as Lagrange multipliers. We treat the case of homogeneous nonlinearities, i.e. , with positive constants β, μi, pi, ri. The exponents are Sobolev subcritical but may be L2-supercritical. Our main result deals with the case in which in dimensions 2 ≤ N ≤ 4. We also consider the cases in which all of these numbers are less than 2 + 4/N or all are bigger than 2 + 4/N.
A cross-species comparison of corticogeniculate structure and function
Authors: HASSE J. MICHAEL , BRIGGS FARRAN
Published: November 2017

The corticogeniculate circuit is an evolutionarily conserved pathway linking the primary visual cortex with the visual thalamus in the feedback direction. While the corticogeniculate circuit is anatomically robust, the impact of corticogeniculate feedback on the visual response properties of visual thalamic neurons is subtle. Accordingly, discovering the function of corticogeniculate feedback in vision has been a particularly challenging task. In this review, the morphology, organization, physiology, and function of corticogeniculate feedback is compared across mammals commonly studied in visual neuroscience: primates, carnivores, rabbits, and rodents. Common structural and organizational motifs are present across species, including the organization of corticogeniculate feedback into parallel processing streams in highly visual mammals.
OVERLEVERAGING, FINANCIAL FRAGILITY, AND THE BANKING–MACRO LINK: THEORY AND EMPIRICAL EVIDENCE
Authors: Mittnik Stefan , Semmler Willi
Published: November 2017

We analyze the consequences of overleveraging and the potential for destabilizing effects from financial- and real-sector interactions. In a theoretical model, we demonstrate that, in the presence of regime-dependent macro feedback relations, a highly leveraged banking system can result in instabilities and downward spirals. To investigate this question empirically, we analyze time series from eight advanced economies on industrial production and the components of the country-specific financial stress indices constructed by the IMF. Employing nonlinear, multiregime vector autoregressions, we examine how industrial production is affected by the individual risk drivers making up the indices. Our results strongly suggest that financial-sector stress has a substantial, nonlinear influence on economic activity and that individual risk drivers affect output rather differently across stress regimes and across groups of countries.
Maternal depression symptoms are highly prevalent among food-insecure households in Ethiopia
Authors: Gebreyesus Seifu Hagos , Endris Bilal Shikur , Hanlon Charlotte , Lindtjørn Bernt
Published: November 2017

Objective

We aimed to evaluate the association between household food insecurity and maternal depression in Ethiopia.

Design/Setting/Subjects

In 2014, we conducted a cross-sectional study in southern Ethiopia, including 591 food-secure and 2500 food-insecure households. We measured depression status of women using the Patient Health Questionnaire-9 validated for Ethiopia, with a cut-off of ≥5. We evaluated household-level food insecurity using a validated Household Food Insecurity Access Scale. We applied Bayesian modelling to evaluate the relationship between food insecurity and maternal depression accounting for other observed characteristics.

Results

Among the analytic sample, 80·8 (95 % CI 79·4, 82·2) % of women were living in food-insecure households. The overall prevalence of probable depression (mild and moderate forms) was 4·7 (95 % CI 4·1, 5·6) %. All individual depressive symptoms had a significantly higher prevalence in the food-insecure group, except for suicidal ideation (but small numbers; P<0·001). In the Bayesian model adjusting for paternal characteristics, there was a significant dose–response linear relationship (trend) between household food insecurity and maternal depression (P<0·01). The adjusted OR (95 % Bayesian credible interval) for depression for differing levels of food insecurity were: mild food insecurity, 3·29 (1·63, 6·18); moderate, 3·82 (1·91, 7·45); severe, 12·50 (3·38, 32·70).

Conclusions

The study documented a high burden of depression among women who lived in food-insecure households. Given this finding, we recommend integrating mental health in the livelihood programmes in areas suffering from food insecurity.
Criminal Politics: An Integrated Approach to the Study of Organized Crime, Politics, and Violence
Authors: Barnes Nicholas
Published: November 2017

Over the last decade, organized criminal violence has reached unprecedented levels and has caused as much violent death globally as direct armed conflict. Nonetheless, the study of organized crime in political science remains limited because these organizations and their violence are not viewed as political. Building on recent innovations in the study of armed conflict, I argue that organized criminal violence should no longer be segregated from related forms of organized violence and incorporated within the political violence literature. While criminal organizations do not seek to replace or break away from the state, they have increasingly engaged in the politics of the state through the accumulation of the means of violence itself. Like other non-state armed groups, they have developed variously collaborative and competitive relationships with the state that have produced heightened levels of violence in many contexts and allowed these organizations to gather significant political authority. I propose a simple conceptual typology for incorporating the study of these organizations into the political violence literature and suggest several areas of future inquiry that will illuminate the relationship between violence and politics more generally.
Regions of Exception
Authors: Pepinsky Thomas B.
Published: November 2017

Regions of exception play a critical role in contemporary world politics: they are sites of civil conflict, economic backwardness, secessionist movements, opposition party support, and challenges to contemporary national projects. I argue in this article that the mainstream methodological language for understanding subnational politics renders such important cases illegible precisely because of these regions’ distinct histories and social structures. Using case materials drawn from contemporary Southeast Asia, I illustrate how to conceptualize regions of exception as representing particular tensions between the insights from comparative politics and area studies, with challenges for a purist view of causal inference in political science. Recognizing the challenges presented by regions of exception will help political scientists to better grasp key issues in contemporary world politics.
THE UNCERTAIN IMPACT OF ANGLO/LATINO CONTACT ON ANGLOS’ IMMIGRATION POLICY VIEWS
Authors: Taylor Marylee C. , Krysan Maria , Hall Matthew
Published: November 2017

This project draws on psychological and sociological social psychology to investigate immigration policy opinions among native-born non-Hispanic Whites. Using data from a suburban Chicago-area county that has seen substantial growth in the Latino immigrant population, we examine Anglos’ opinions on three dimensions of immigration policy: preferred immigration rate, resistance to immigration, and assistance for immigrants. Our central hypothesis is that liberalizing effects of Anglo/Latino interpersonal contact are conditioned on Anglos’ recognition of hardships and barriers faced by Latinos. Five of the six interaction effects we estimated were highly significant: Personal contact with Latinos does promote more positive, progressive immigration policy opinions, but only among some Anglos—those who were acquainted with immigrants who had run afoul of immigration law or believed there is substantial local discrimination against Latinos. The results are reminiscent of James Kluegel’s (1985) analysis of White Americans’ views about affirmative action: “If there isn’t a problem, you don’t need a solution.” Affirmation of local anti-Latino discrimination was the stronger moderator of contact effects and also showed main effects on immigration policy opinion stronger than the effects of interpersonal contact. Denial of anti-Latino discrimination may be a means used by Anglos to defend their group position.
Effect of neonatal orally administered S-allyl cysteine in high-fructose diet fed Wistar rats
Authors: Lembede B. W. , Erlwanger K. H. , Nkomozepi P. , Chivandi E.
Published: November 2017

S-allyl cysteine (SAC) has antioxidant, antidiabetic and antiobesity properties. We hypothesized that neonatal oral administration of SAC would protect rats against neonatal and adulthood high-fructose diet-induced adverse metabolic outcomes in adulthood. In total, 112 (males=56; females=56), 4-day-old Wistar rat pups were randomly allocated to groups and administered the following treatment regimens daily for 15 days from postnatal day (PND) 6–20: group I – 10 ml/kg distilled water, group II – 10 ml/kg 20% fructose solution (FS), group III – 150 mg/kg SAC and group IV – SAC+FS. On PND 21, the pups were weaned and allowed to grow on a standard rat chow (SRC) until PND 56. The rats from each treatment regimen were then randomly split into two subgroups: one on a SRC and plain drinking water and another on SRC and 20% FS as drinking fluid and then subjected to these treatment regimens for 8 weeks after which they were euthanized and tissues collected for analyzes. Neonatal oral administration of SAC attenuated the neonatal high-fructose diet-induced programming for hepatic lipid accretion in adulthood but not against adulthood high-fructose diet-induced visceral obesity. Neonatal oral administration of SAC programmes for protection against neonatal fructose-induced programming for hepatic lipid accumulation thus could potentially protect against fat-mediated liver derangements in adult life.
A Kantian system of constitutional justice: Rights, trusteeship, balancing
Authors: SWEET ALEC STONE , PALMER ERIC
Published: November 2017

The article develops a Kantian account of constitutional justice: the explication of those structural features of a legal system whose purpose is to optimise a polity’s capacity to achieve a Rightful condition. The People, in enacting a rights-based constitution, have placed their freedom in trust. Rights ground a system of reciprocal freedom among individuals, while conferring on officials the authority to make and enforce law, subject to constraints laid down by the Universal Principle of Right [UPR]. A constitutional court, the trustee of the regime, supervises the rights-regarding acts of all other officials, assesses the reasons officials give when they take decisions that burden rights, and invalidates those acts when reasons given to justify such burdens fail to meet the demands of the UPR. Although some rights will be expressed in absolute terms, most will be qualified by a limitation clause. In adjudicating qualified rights, the court can do no better than to adopt the proportionality principle. The UPR, operationalised through proportionality analysis, lays down a basic criterion for the legitimacy of all law. Because Public, International, and Cosmopolitan Right share certain micro-foundations in common, we can extend the analysis to transnational systems of rights protection.
Smoking Abstinence Twelve Months after an Acute Coronary Syndrome
Authors: Rocha Vânia , Guerra Marina P. , Lemos Marina S. , Maciel Júlia , Williams Geoffrey C.
Published: November 2017

Studies on the cognitive working mechanism of smoking cessation in high-risk populations are few and much needed, and identifying long-term psychosocial factors to smoking cessation are relevant to improve intervention for cardiac patient groups. This longitudinal study followed patients who smoked and suffered an acute coronary syndrome from hospitalization to 12 months after clinical discharge. Questionnaires were administered to assess nicotine dependence, behavioral dependence, autonomous self-regulation, perceived competence, social support, anxiety, depressive symptoms and meaning in life at baseline, six months and twelve months after clinical discharge. The results showed that anxiety (F(2, 62) = 28.10, p < .001, ηp2 = .48) and depressive symptoms (F(2, 62) = 10.42, p < .001, ηp2 = .25) decreased over time, whereas meaning in life (F(2, 61) = 44.77, p < .001, ηp2 = .59) and social support increased (t(63) = –4.54, p < .001, 95% IC[–11.05, 4.29], η2 =.25). Smoking dependence was negatively predicted by change in perceived competence (B = –2.25, p = .011, 95% IC[.02, .60]) and positively by change in depressive symptoms (B =.37, p = .042, 95% IC[1.01, 2.05]) 12 months after clinical discharge. Nicotine dependence (t(17) = 2.76, p = .014, 95% IC[.39, 2.94], η2 =.31) and the number of cigarettes smoked per day (t(17) = 4.48, p < .001, 95% IC[5.49, 15.29], η2 =.54) decreased over time, whereas behavioral dependence increased among smokers (t(17) = –2.37, p = .030, 95% IC[–4.30, 2.54], η2 =.25). This study suggests that long term abstinence in cardiac patients may be enhanced by psychological interventions addressing perceived competence, depressive symptoms and behavioral dependence.
Beyond Precision Weed Control: A Model for True Integration
Authors: Young Stephen L.
Published: November 2017

Precision means being exact and accurate and is an important management component for cropping systems. However, precision does not mean integration, which encompasses spatial and temporal dimensions and is a necessary practice rivaling precision. True IWM merges precision and integration by incorporating advanced technology that allows for greater flexibility of inputs and enhanced responsiveness to field conditions. Examples of this approach are non-existent due to a lack of suitable technological tools and a need for a paradigm shift. Herein a potential model startup company is offered as a guide to advance beyond precision weed control to true integration. The critical components of such a company include grower connections, investor support, proven and reliable technology, and adaptability and innovation in the agricultural technology market. The company with the vision and incentive to make true IWM a reality will be the first to more fully integrate available tools using technology, thus helping many growers overcome ongoing challenges associated with resistance, soil erosion, drift, and weed seedbanks.
Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility
Authors: Chintalapudi Sumana R. , Maria Doaa , Di Wang Xiang , Bailey Jessica N. Cooke ,   NEIGHBORHOOD consortium, Allingham Rand , Brilliant Murray , Budenz Don , Fingert John , Gaasterland Douglas , Gaasterland Teresa , Haines Jonathan L. , Hark Lisa , Hauser Michael , Igo Rob , Hee Kang Jae , Kraft Peter , Lee Richard , Lichter Paul , Liu Yutao , Moroi Syoko , Pasquale Louis R. , Pericak-Vance Margaret , Realini Anthony , Rhee Doug , Richards Julia R. , Ritch Robert , Schuman Joel , Scott William K. , Singh Kuldev , Sit Arthur , Vollrath Douglas , Wollstein Gadi , Zack Don ,   International Glaucoma Genetics consortium, Aung Tin , Bonnemaijer Peter , Cheng Cheng-Yu , Craig Jamie , van Duijn Cornelia , Gharahkhani Puya , Iglesias Gonzalez Adriana , Hammond Christopher J. , Hewitt Alex , Hoehn Rene , Jonansson Fridbert , Khawaja Anthony , Chuen Khor Chiea , Klaver Caroline C. W. , Lotery Andrew , Mackey David , MacGregor Stuart , Pang Calvin , Pasutto Francesca , Stefansson Kári , Thorleifsson Gudmar , Thorsteinsdottir Unnar , Vitart Veronique , Vithana Eranga , Young Terri , Zeller Tanja , Hysi Pirro G. , Wiggs Janey L. , Williams Robert W. , Jablonski Monica M.
Published: November 2017

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.
Regulatory T cells control toxicity in a humanized model of IL-2 therapy
Authors: Li Yan , Strick-Marchand Helene , Lim Ai Ing , Ren Jiazi , Masse-Ranson Guillemette , Dan Li  , Jouvion Gregory , Rogge Lars , Lucas Sophie , Bin Li  , Di Santo James P.
Published: November 2017

While patient selection and clinical management have reduced high-dose IL-2 (HDIL2) immunotherapy toxicities, the immune mechanisms that underlie HDIL2-induced morbidity remain unclear. Here we show that dose-dependent morbidity and mortality of IL-2 immunotherapy can be modeled in human immune system (HIS) mice. Depletion of human T cell subsets during the HDIL2 treatment reduces toxicity, pointing to the central function of T cells. Preferential expansion of effector T cells secondary to defective suppressive capacity of regulatory T (Treg) cells after HDIL2 therapy further underscores the importance of Tregin the maintenance of immune tolerance. IL-2 toxicity is induced by selective depletion or inhibition of Tregafter LDIL2 therapy, and is ameliorated in HDIL2-treated HIS mice receiving the PIM-1 kinase inhibitor, Kaempferol. Modeling IL-2 pathophysiology in HIS mice offers a means to understand the functions of effector and regulatory T cells in immune-mediated toxicities associated with cancer immunotherapy.
Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy
Authors: Li Wenming , Zhu Jinqiu , Dou Juan , She Hua , Tao Kai , Xu Haidong , Yang Qian , Mao Zixu
Published: November 2017

Endoplasmic reticulum (ER) and lysosomes coordinate a network of key cellular processes including unfolded protein response (UPR) and autophagy in response to stress. How ER stress is signaled to lysosomes remains elusive. Here we find that ER disturbance activates chaperone-mediated autophagy (CMA). ER stressors lead to a PERK-dependent activation and recruitment of MKK4 to lysosomes, activating p38 MAPK at lysosomes. Lysosomal p38 MAPK directly phosphorylates the CMA receptor LAMP2A at T211 and T213, which causes its membrane accumulation and active conformational change, activating CMA. Loss of ER stress-induced CMA activation sensitizes cells to ER stress-induced death. Neurotoxins associated with Parkinson’s disease fully engages ER-p38 MAPK–CMA pathway in the mouse brain and uncoupling it results in a greater loss of SNc dopaminergic neurons. This work identifies the coupling of ER and CMA as a critical regulatory axis fundamental for physiological and pathological stress response.
Caldera resurgence driven by magma viscosity contrasts
Authors: Galetto Federico , Acocella Valerio , Caricchi Luca
Published: November 2017

Calderas are impressive volcanic depressions commonly produced by major eruptions. Equally impressive is the uplift of the caldera floor that may follow, dubbed caldera resurgence, resulting from magma accumulation and accompanied by minor eruptions. Why magma accumulates, driving resurgence instead of feeding large eruptions, is one of the least understood processes in volcanology. Here we use thermal and experimental models to define the conditions promoting resurgence. Thermal modelling suggests that a magma reservoir develops a growing transition zone with relatively low viscosity contrast with respect to any newly injected magma. Experiments show that this viscosity contrast provides a rheological barrier, impeding the propagation through dikes of the new injected magma, which stagnates and promotes resurgence. In explaining resurgence and its related features, we provide the theoretical background to account for the transition from magma eruption to accumulation, which is essential not only to develop resurgence, but also large magma reservoirs.
Spectroscopic detection of halogen bonding resolves dye regeneration in the dye-sensitized solar cell
Authors: Parlane Fraser G. L. , Mustoe Chantal , Kellett Cameron W. , Simon Sarah J. , Swords Wesley B. , Meyer Gerald J. , Kennepohl Pierre , Berlinguette Curtis P.
Published: November 2017

The interactions between a surface-adsorbed dye and a soluble redox-active electrolyte species in the dye-sensitized solar cell has a significant impact on the rate of regeneration of photo-oxidized dye molecules and open-circuit voltage of the device. Dyes must therefore be designed to encourage these interfacial interactions, but experimentally resolving how such weak interactions affect electron transfer is challenging. Herein, we use X-ray absorption spectroscopy to confirm halogen bonding can exist at the dye-electrolyte interface. Using a known series of triphenylamine-based dyes bearing halogen substituents geometrically positioned for reaction with halides in solution, halogen bonding was detected only in cases where brominated and iodinated dyes were photo-oxidized. This result implies that weak intermolecular interactions between photo-oxidized dyes and the electrolyte can impact device photovoltages. This result was unexpected considering the low concentration of oxidized dyes (less than 1 in 100,000) under full solar illumination.
High magnesium mobility in ternary spinel chalcogenides
Authors: Canepa Pieremanuele , Bo Shou-Hang , Sai Gautam Gopalakrishnan , Key Baris , Richards William D. , Shi Tan , Tian Yaosen , Wang Yan , Li Juchuan , Ceder Gerbrand
Published: November 2017

Magnesium batteries appear a viable alternative to overcome the safety and energy density limitations faced by current lithium-ion technology. The development of a competitive magnesium battery is plagued by the existing notion of poor magnesium mobility in solids. Here we demonstrate by using ab initio calculations, nuclear magnetic resonance, and impedance spectroscopy measurements that substantial magnesium ion mobility can indeed be achieved in close-packed frameworks (~ 0.01–0.1 mS cm–1 at 298 K), specifically in the magnesium scandium selenide spinel. Our theoretical predictions also indicate that high magnesium ion mobility is possible in other chalcogenide spinels, opening the door for the realization of other magnesium solid ionic conductors and the eventual development of an all-solid-state magnesium battery.
Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma
Authors: Simeoli Raffaele , Montague Karli , Jones Hefin R. , Castaldi Laura , Chambers David , Kelleher Jayne H. , Vacca Valentina , Pitcher Thomas , Grist John , Al-Ahdal Hadil , Wong Liang-Fong , Perretti Mauro , Lai Johnathan , Mouritzen Peter , Heppenstall Paul , Malcangio Marzia
Published: November 2017

Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron–macrophage communication after damage to the peripheral nerve.
An activity-dependent proximity ligation platform for spatially resolved quantification of active enzymes in single cells
Authors: Li Gang , Montgomery Jeffrey E. , Eckert Mark A. , Chang Jae Won , Tienda Samantha M. , Lengyel Ernst , Moellering Raymond E.
Published: November 2017

Integration of chemical probes into proteomic workflows enables the interrogation of protein activity, rather than abundance. Current methods limit the biological contexts that can be addressed due to sample homogenization, signal-averaging, and bias toward abundant proteins. Here we report a platform that integrates family-wide chemical probes with proximity-dependent oligonucleotide amplification and imaging to quantify enzyme activity in native contexts with high spatial resolution. Application of this method, activity-dependent proximity ligation (ADPL), to serine hydrolase and cysteine protease enzymes enables quantification of differential enzyme activity resulting from endogenous changes in localization and expression. In a competitive format, small-molecule target engagement with endogenous proteins in live cells can be quantified. Finally, retention of sample architecture enables interrogation of complex environments such as cellular co-culture and patient samples. ADPL should be amenable to diverse probe and protein families to detect active enzymes at scale and resolution out of reach with current methods.
Quenching protein dynamics interferes with HIV capsid maturation
Authors: Wang Mingzhang , Quinn Caitlin M. , Perilla Juan R. , Zhang Huilan , Shirra Randall , Hou Guangjin , Byeon In-Ja , Suiter Christopher L. , Ablan Sherimay , Urano Emiko , Nitz Theodore J. , Aiken Christopher , Freed Eric O. , Zhang Peijun , Schulten Klaus , Gronenborn Angela M. , Polenova Tatyana
Published: November 2017

Maturation of HIV-1 particles encompasses a complex morphological transformation of Gag via an orchestrated series of proteolytic cleavage events. A longstanding question concerns the structure of the C-terminal region of CA and the peptide SP1 (CA–SP1), which represents an intermediate during maturation of the HIV-1 virus. By integrating NMR, cryo-EM, and molecular dynamics simulations, we show that in CA–SP1 tubes assembled in vitro, which represent the features of an intermediate assembly state during maturation, the SP1 peptide exists in a dynamic helix–coil equilibrium, and that the addition of the maturation inhibitors Bevirimat and DFH-055 causes stabilization of a helical form of SP1. Moreover, the maturation-arresting SP1 mutation T8I also induces helical structure in SP1 and further global dynamical and conformational changes in CA. Overall, our results show that dynamics of CA and SP1 are critical for orderly HIV-1 maturation and that small molecules can inhibit maturation by perturbing molecular motions.
NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis
Authors: Peri Suraj , Izumchenko Evgeny , Schubert Adrian D. , Slifker Michael J. , Ruth Karen , Serebriiskii Ilya G. , Guo Theresa , Burtness Barbara A. , Mehra Ranee , Ross Eric A. , Sidransky David , Golemis Erica A.
Published: November 2017

Squamous cell carcinomas of the head and neck (SCCHN) affect anatomical sites including the oral cavity, nasal cavity, pharynx, and larynx. Laryngeal cancers are characterized by high recurrence and poor overall survival, and currently lack robust molecular prognostic biomarkers for treatment stratification. Using an algorithm for integrative clustering that simultaneously assesses gene expression, somatic mutation, copy number variation, and methylation, we for the first time identify laryngeal cancer subtypes with distinct prognostic outcomes, and differing from the non-prognostic laryngeal subclasses reported by The Cancer Genome Atlas (TCGA). Although most common laryngeal gene mutations are found in both subclasses, better prognosis is strongly associated with damaging mutations of the methyltransferasesNSD1andNSD2, with findings confirmed in an independent validation cohort consisting of 63 laryngeal cancer patients. Intriguingly, NSD1/2 mutations are not prognostic for nonlaryngeal SCCHN. These results provide an immediately useful clinical metric for patient stratification and prognostication.
DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells
Authors: Sato Hiro , Niimi Atsuko , Yasuhara Takaaki , Permata Tiara Bunga Mayang , Hagiwara Yoshihiko , Isono Mayu , Nuryadi Endang , Sekine Ryota , Oike Takahiro , Kakoti Sangeeta , Yoshimoto Yuya , Held Kathryn D. , Suzuki Yoshiyuki , Kono Koji , Miyagawa Kiyoshi , Nakano Takashi , Shibata Atsushi
Published: November 2017

Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs.
Origami silicon optoelectronics for hemispherical electronic eye systems
Authors: Zhang Kan , Jung Yei Hwan , Mikael Solomon , Seo Jung-Hun , Kim Munho , Mi Hongyi , Zhou Han , Xia Zhenyang , Zhou Weidong , Gong Shaoqin , Ma Zhenqiang
Published: November 2017

Digital image sensors in hemispherical geometries offer unique imaging advantages over their planar counterparts, such as wide field of view and low aberrations. Deforming miniature semiconductor-based sensors with high-spatial resolution into such format is challenging. Here we report a simple origami approach for fabricating single-crystalline silicon-based focal plane arrays and artificial compound eyes that have hemisphere-like structures. Convex isogonal polyhedral concepts allow certain combinations of polygons to fold into spherical formats. Using each polygon block as a sensor pixel, the silicon-based devices are shaped into maps of truncated icosahedron and fabricated on flexible sheets and further folded either into a concave or convex hemisphere. These two electronic eye prototypes represent simple and low-cost methods as well as flexible optimization parameters in terms of pixel density and design. Results demonstrated in this work combined with miniature size and simplicity of the design establish practical technology for integration with conventional electronic devices.
HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
Authors: Du Weinan , Zhang Luchang , Brett-Morris Adina , Aguila Brittany , Kerner Janos , Hoppel Charles L. , Puchowicz Michelle , Serra Dolors , Herrero Laura , Rini Brian I. , Campbell Steven , Welford Scott M.
Published: November 2017

Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A (CPT1A), as a direct HIF target gene. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. Droplet formation occurs independent of lipid source, but only when CPT1A is repressed. Functionally, repression of CPT1A is critical for tumor formation, as elevated CPT1A expression limits tumor growth. In human tumors, CPT1A expression and activity are decreased versus normal kidney; and poor patient outcome associates with lower expression of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty acid metabolism as essential for ccRCC tumorigenesis.