bluuebunny/crossref_metadata_2025 huggingface dataset:
Masculine gender‐role adherence indicates conflict resolution patterns in heterosexual adolescent couples: A dyadic, observational study
Authors: Rogers Adam A. , Ha Thao , Byon Jennifer , Thomas Clare
Published: January 2020

Introduction

Conflict resolution in romantic relationships is a critical skillset that relates to individual and relational well‐being. In adolescence, heterosexual romantic relationships are highly gendered, and norms for traditional masculinity (a bravado focused on interpersonal dominance) may be relevant in shaping how adolescents navigate disagreements. Therefore, we examined the associations between adolescents’ conformity to norms for traditional masculinity and their conflict resolution in their romantic relationships.

Method

Using a sample of 91 heterosexual adolescent couples from the Southwest United States (Mage = 16.50, SD = .90; 44% White, 42% Latinx), we examined how self‐reported conformity to traditional masculinity predicted independent observer ratings of negotiation, coercion, and avoidance strategies during a lab‐based conflict and jealousy discussion task.

Results

Results of actor‐partner interdependence models (APIMs) indicated that more highly masculine adolescents generally displayed less conflict negotiation and more coercion during the discussion task. Dyadic and gendered patterns characterized masculinity's associations with negotiation and coercion. Masculinity was unassociated with conflict avoidance.

Conclusions

Adolescents in heterosexual relationships that adhere more rigidly to gendered norms for traditional masculinity may be challenged in acquiring skills for constructive conflict resolution with a romantic partner. Adolescent romantic relationships are a socialization context in which many individuals develop the skills for future romantic relationships, including those into young adulthood. Addressing masculine gender roles in adolescence may help promote the development of positive conflict management and overall romantic functioning in youth.
Best pasture management practice adoption and sediment abatement
Authors: Lambert Dayton M. , Clark Christopher D. , Medwid Laura J. , Hawkins Shawn A. , McClellan Hannah A.
Published: January 2020

Research on producer willingness to adopt individual best pasture management practices (BMPs) is extensive, but less attention has been paid to producers simultaneously adopting multiple, complementary BMPs. Applications linking primary survey data on BMP adoption to water quality biophysical models are also limited. A choice-experiment survey of livestock producers is analyzed to determine willingness to adopt pasture BMPs. Sediment abatement curves are derived by linking estimates of producer responsiveness to incentives to adopt rotational grazing with a biophysical simulation model. Current cost share rates of $24/acre should yield a 12% decrease in sediment loading from pastures.
The Necessary Complexity of Consent: Rules and Norms in EU Treaty Making
Authors: HODSON Dermot , MAHER Imelda
Published: January 2020

The idea that EU treaties have become too difficult to amend is a recurring one. This Article explores changing national constitutional rules and norms in the consent stage of EU treaty making in twenty-eight Member States between 1950 and 2016, asking how parliaments, people, and courts came to be much more significant for consent, what the consequences of this shift are, and offering some tentative proposals as to how the challenges this raises could be addressed. EU treaty making has become more complex, but we argue that treaties should be more rather than less difficult to amend where concerns over two-level legitimacy rather than two-level games predominate.
The Shifting Geometry of Union Citizenship: A Supranational Status from Transnational Rights
Authors: COUTTS Stephen
Published: January 2020

This Article analyses recent developments in Union citizenship, in particular the relationship between Articles 20 and 21 TFEU. In doing so, it divides Union citizenship into a transnational and a supranational dimension with the transnational dimension having two sub-dimensions: social integration and autonomy. It is argued that we are seeing an increased emphasis on the responsibility of the individual citizen in the context of the transnational dimension and a clear linkage between the transnational and supranational dimensions. The result of these two moves is a status which continues to emphasise the relationship between the Union citizen and the communities represented by Member States, while framing this with a more prominent supranational dimension.
Institutional roots of economic decline: lessons from Italy
Authors: Simoni Marco
Published: January 2020

The economic decline of Italy between the mid-1990s and the outset of the financial crisis is a critical case in European political economy because its model of capitalism was deeply reformed at the time when its decline commenced. This paper argues that the Italian economic stagnation cannot be attributed to the lack of market-friendly reforms in a globalized economic context, as argued by previous literature. Instead, Italian economic decline is a consequence of institutional change which on the one hand has destroyed previous institutional complementarities, and on the other hand has led to an incoherent, or ‘hybrid,’ capitalist setting. Under the lenses of the Varieties of Capitalism approach, this paper reviews the main reforms in the fields of corporate governance and finance as well as in the labor market. It shows that such reforms established new institutions alternatively apt to support both strategic coordination and market coordination, resulting in institutional incoherence, and mixed incentives. In the short-run, incoherent reforms have reduced the availability of capital to SMEs; in the longer-run, they failed to give actors incentives to pursue innovation. This paper contributes theories of economic growth/decline focused on the supply-side of the economy and it is compatible with other – non-rival – explanations focused on the demand-side.
A taxonomic revision of the Early Devonian dalmanitid trilobite Kasachstania Maksimova, 1972 from central Kazakhstan
Authors: Randolfe Enrique A. , Rustán Juan José , Bignon Arnaud
Published: January 2020

The dalmanitid trilobite Kasachstania Maksimova, 1972, previously reported from the Lower Devonian of Kazakhstan and North America (USA) and the upper Silurian–Lower Devonian of South America (Bolivia and Argentina), is revised. Kasachstania kasachstanica (Balashova in Maksimova,1968) and K. septicostata (Maksimova, 1968) are regarded as junior synonyms of the type species K. saryarkensis (Maksimova, 1960), all from the Lower Devonian of the type locality in central Kazakhstan (northern Balkhash). On the basis of a new diagnosis, K. ulrichi ulrichi (Delo, 1940) from the Emsian of the United States, K. ulrichi asiatica (Maksimova, 1968), K. pristina (Maksimova, 1968), and K. alperovichi Pour et al., 2019, from the Lower Devonian of Kazakhstan, K. andii (Kozłowski, 1923) from the upper Silurian–Lower Devonian of Bolivia, and K. gerardoi Edgecombe and Ramsköld, 1994, from the upper Silurian–Lower Devonian of Bolivia and Argentina are excluded from Kasachstania. This genus, represented only by K. saryarkensis and K. kiikbaica (Maksimova, 1968), is restricted to the Lower Devonian of central Kazakhstan, corresponding to the Balkhash–Mongolo–Okhotsk province in the paleobiogeographic context of the Old World Realm, instead of being nearly cosmopolitan as previously considered. In addition, we provide some remarks about Saryarkella Maksimova, 1978b, a monospecific dalmanitid genus largely overlooked although valid from the Emsian of the same area in central Kazakhstan.
Effects of age, salinity and temperature on the metamorphosis and survival ofCapitulum mitellacyprids (Cirripedia: Thoracica: Scalpellomorpha)
Authors: Rao Xiaozhen , Lin Gang
Published: January 2020

Capitulum mitellais a tropical/sub-tropical intertidal barnacle of high economic value. However, no studies have yet focused on the effects of the extrinsic and intrinsic factors that affect the metamorphosis of this species. The current study stored cyprids at room temperature (24–26°C) and low temperature (7°C) and then compared the effects of age and storage temperature on cyprid metamorphosis. The effects of salinity and temperature on cyprid metamorphosis and survival were examined. Results showed the following. (1) Young 0-day cyprids were not competent to metamorphose, andC. mitellacyprids had a pre-competent phase. (2) The cyprid metamorphosis percentage at different storage temperatures with the same age was higher at room temperature than at 7°C. Low temperature storage of cyprids appeared to be unsuitable forC. mitella. The ideal storage time at room temperature for cyprids was 3–5 days. (3) The cyprids could complete metamorphosis at a salinity range of 20–45 mg l−1, and the optimum salinity range for metamorphosis was 25–35 mg l−1. At 15 mg l−1salinity, the cyprids could survive but failed to metamorphose. (4) The cyprids could survive and complete metamorphosis at 18–36°C, and the optimum temperature range for metamorphosis was 21–33°C. The metamorphosis ofC. mitellacyprids can tolerate a wide spectrum of salinity and temperature, which is related to the distribution location, habitat environment and lifestyle. Results of this study may provide a basis for the settlement biology, recruitment ecology and aquaculture of this species.
Velocity and Force Transfer Performance Analysis of a Parallel Hip Assistive Mechanism
Authors: Li Jianfeng , Zhang Leiyu , Dong Mingjie , Zuo Shiping , He Yandong , Zhang Pengfei
Published: January 2020

Against the backdrop of accelerated ageing around the globe, an increasing number of individuals suffer from hip motion disability and gait disorders. In this paper, the performance analysis of a novel parallel assistive mechanism with 2 DOF for hip adduction/abduction (AB/AD) and flexion/extension (FL/EX) assistance is completed and evaluated, particularly the velocity and force transfer features. The analysis shows that the assistive mechanism has advantages of fine motion assistive isotropy, high force transfer ratio and large force isotropic radius, which indicates that the parallel assistive mechanism is suitable for hip AB/AD and FL/EX assistance.
New records and genetic diversity ofMycoplasma ovisin free-ranging deer in Brazil
Authors: André Marcos Rogério , Duarte José Maurício Barbanti , Gonçalves Luiz Ricardo , Sacchi Ana Beatriz Vieira , Jusi Márcia Mariza Gomes , Machado Rosangela Zacarias
Published: January 2020

Cervids represent a mammal group which plays an important role in the maintenance of ecological balance. Recent studies have highlighted the role of these species as reservoirs for several arthropods-borne pathogens. Globally, hemotropic mycoplasmas (haemoplasmas) are emerging or remerging bacteria that attach to red blood cells of several mammals species causing hemolytic anaemia. Therefore, the aim of this study was to investigate the occurrence and assess the phylogenetic positioning ofMycoplasma ovisin free-ranging deer from Brazil. Using a polymerase chain reaction targeting the 16S rRNA region, 18 (40%) out of 45 sampled deer were positive toM. ovis.Among the nine sequences analysed, four distinct genotypes were identified. The sequences detected in the present study were closely related to sequences previously identified in deer from Brazil and the USA. On the other hand, the Neighbour-Net network analysis showed that the human-associatedM. ovisgenotypes were related to genotypes detected in sheep and goats. The present study shows, for the first time, the occurrence ofM. ovisinMazama gouazoubiraandMazama bororodeer species, expanding the knowledge on the hosts harbouring this haemoplasma species. Once several deer species have your population in decline, additional studies are needed to evaluate the pathogenicity ofM. ovisamong deer populations around the world and assess its potential as reservoir hosts to human infections.
Mentalizing in mothers and children with type 1 diabetes
Authors: Costa-Cordella Stefanella , Luyten Patrick , Cohen Diego , Mena Francisca , Fonagy Peter
Published: January 2020

Studies suggest that the relationship between psychosocial well-being and type 1 diabetes (T1D) is bidirectional, with T1D typically having a negative influence on psychological functioning, which in turn negatively affects the course of T1D. Here, we investigate the potential role of the capacity for mentalizing, or reflective functioning, in children and their mothers in diabetes control. We tested differences in mentalizing as assessed by the Reflective Functioning Scale in two groups of mother–son dyads with good (GDC) versus poor (PDC) diabetes control. Fifty-five boys (8–12 years old) and their mothers were recruited from the Juvenile Diabetes Foundation in Santiago, Chile. The mothers were interviewed with the Parental Development Interview and the children with the Child Attachment Interview, and both were scored for reflective functioning by using the Reflective Functioning Scale. Self-report measures of stress and diabetes outcomes were completed by the mothers and children, and levels of glycated hemoglobin (HbA1c) were assessed as an index of diabetes control. The results showed that both maternal and child reflective functioning were higher in the GDC than the PDC group and were negatively correlated with HbA1c in the total sample. Our findings suggest an important role for mentalizing in diabetes outcomes, but further prospective research is needed.
Geometry and Architectural Planning at Göbekli Tepe, Turkey
Authors: Haklay Gil , Gopher Avi
Published: January 2020

The site of Göbekli Tepe in southeastern Turkey keeps fascinating archaeologists as it is being exposed. The excavation since 1995 has been accompanied by a lively discussion about the meaning and implications of its remarkable early Neolithic megalithic architecture, unprecedented in its monumentality, complexity and symbolic content. The building history and the chronological relations between the different structures (enclosures), however, remain in many ways a challenge and open to further analysis. The study presented here is an attempt to contribute in this direction by applying a preliminary architectural formal analysis in order to reconstruct aspects of the architectural design processes involved in the construction of the monumental enclosures. This is done under the premise that such investigation would shed light on thechaîne opératoireof the enclosures' construction and their history, thus enabling a fresh look as well as an evaluation of past suggestions regarding these structures and the people who built them. Indeed, the results of the analysis brought to light an underlying geometric pattern which offers a new understanding of the assemblage of architectural remains indicating that three of the stone-built large enclosures were planned and initially built as a single project.
Characterization of isolated bovine preantral follicles based on morphology, diameter and cell number
Authors: Candelaria Juliana I. , Denicol Anna C.
Published: January 2020

Preantral follicles are a potential reservoir of oocytes to be used in assisted reproductive technologies. With the increasing interest in developing techniques to grow preantral follicles in vitro, and as the bovine emerges as an appropriate model species to understand human folliculogenesis, the establishment of an accurate classification of developmental stages is needed. Classification of bovine preantral follicles has been mostly based on histological analysis and estimation models, which may not translate well to correctly characterize preantral follicles isolated from the ovary. In this study, we classified bovine preantral follicles by morphology upon isolation, determined diameter and number of granulosa cells by direct counting, and compared our results with previous studies reporting bovine preantral follicle classification. Follicles were isolated via homogenization of ovary tissue and classified into primary, early secondary and secondary stage based on morphology and number of layers of granulosa cells. Diameter was individually measured and Hoechst 33342 was used as a nuclear stain to count granulosa cells. We found that follicles classified by morphology into primary, early secondary, and secondary had different mean diameter and cell number (P < 0.01); cell number and diameter were positively correlated, as were cell density and cell number in each developmental stage (P < 0.01). Results obtained here were mostly in agreement with previous classifications based on histological sections and on isolated follicles, with some discrepancies. The present data add accuracy to classification of bovine preantral follicles that is critical to optimize culture conditions to produce developmentally competent oocytes.
A hedonic valuation of sanitation services in Guatemala
Authors: Vásquez William F. , Beaudin Laura
Published: January 2020

Many developing countries lack universal sanitation services for residents. Years of inappropriate disposal of solid waste and wastewater have increased the potential for devastating environmental and health issues. An economic valuation of sanitation services may help in planning investment projects by demonstrating the benefits that households derive from having access to improved sanitation. We examine Guatemala as a case study and employ a series of hedonic models to estimate the value that households in Guatemala assign to the sanitation services of solid waste collection and connections to sewer infrastructure. Findings indicate that residents are willing to pay higher rents for both wastewater and solid waste removal. Policy implications are discussed.
Older peoples' willingness to delay social security claiming
Authors: Maurer Raimond , Mitchell Olivia S.
Published: January 2020

We have designed and implemented an experimental module in the 2014 Health and Retirement Study to measure older persons' willingness to defer claiming of Social Security benefits. Under the current system’ status quo where delaying claiming boosts eventual benefits, we show that 46% of the respondents would delay claiming and work longer. If respondents were instead offered an actuarially fair lump sum payment instead of higher lifelong benefits, about 56% indicate they would delay claiming. Without a work requirement, the average amount needed to induce delayed claiming is only $60,400, while when part-time work is stipulated, the amount is slightly higher, $66,700. This small difference implies a low utility value of leisure foregone, of under 20% of average household income.
The “New” Cultural Cleavage in Western Europe: A Coalescence of Religious and Secular Value Divides?
Authors: Pless Anna , Tromp Paul , Houtman Dick
Published: January 2020

Moral traditionalism versus progressiveness and secular authoritarianism versus libertarianism are often understood as central to the same “new” cultural cleavage in politics. Despite the often-found sizable correlations between these two cultural value divides, the present paper theorizes that this relationship is not a cross-contextual constant, but rather a specific feature of secularized contexts where moral traditionalism is relatively marginal. We test this theory by means of a two-stage statistical analysis of the data from the four waves of the European Values Study (1981–2008) for 17 Western European countries. Our findings confirm that the two value divides are most strongly connected in the most secularized contexts because the latter are least morally traditionalist. While the two cultural divides hence tend to be distinct in more religious Western-European countries, they tend to coalesce into one single “new” cultural divide in more secular ones.
Everyday Practices of Toleration: The Interfaith Foundations of Peace Accords in Sierra Leone
Authors: Day Joel
Published: January 2020

Under what conditions can faith leaders influence peace in civil wars? The ongoing conflict in Congo, Syria, and Yemen indicate that faith leaders can fuel sectarian divide, but also intervene on the side of peace. Drawing on experiences in Sierra Leone's civil war, this paper highlights the role of faith leaders as moral guarantors of peace processes, with respondent former rebels indicating that without interfaith delegations personally bringing the peace accord to their remote jungle camps, they would not have trusted the UN-led process. Ethnographic analysis and over 60 field interviews with former combatants and religious leaders, presents a model for answering why faith leaders were central in terminating this conflict. Combatant's personal experience with a diverse mixture of Christian, Traditional, and Islamic leaders contributed to high confidence in peace accords, due to interfaith practices deeply embedded within the culture and shows the dispositions, rituals, and interfaith practices that provided the cultural foundations for successful interfaith intervention. The paper ends with generalizations for other interfaith groups seeking to intervene in conflict.
Temporal improvements in loco-regional failure and survival in patients with anal cancer treated with chemo-radiotherapy: treatment cohort study (1990–2014)
Authors: Sekhar Hema , Malcomson Lee , Kochhar Rohit , Sperrin Matthew , Alam Nooreen , Chakrbarty Bipasha , Fulford Paul E. , Wilson Malcolm S. , O’Dwyer Sarah T. , Saunders Mark P. , Renehan Andrew G.
Published: January 2020

Background

We evaluated oncological changes in patients with squamous cell carcinoma of the anus (SCCA) treated by chemoradiotherapy (CRT) from a large UK institute, to derive estimates of contemporary outcomes.

Methods

We performed a treatment-cohort analysis in 560 patients with non-metastatic SCCA treated with CRT over 25 years. The primary outcomes were 3-year loco-regional failure (LRF), 5-year overall survival (OS), and 5-year cancer-specific survival (CSS). We developed prediction models; and overlaid estimates on published results from historic trials.

Results

Age distributions, proportions by gender and cT stage remained stable over time. The median follow-up was 61 (IQR: 36–79) months. Comparing the first period (1990–1994) with the last period (2010–2014), 3-year LRF declined from 33 to 16% (Ptrends < 0.001); 5-year OS increased from 60% to 76% (Ptrends = 0.001); and 5-year CCS increased from 62% in to 80% (Ptrends = 0.001). For 2020, the models predicted a 3-year LRF of 14.7% (95% CIs: 0–31.3); 5-year OS of 74.7% (95% CIs: 54.6–94.9); and 5-year CSS of 85.7% (95% CIs: 75.3–96.0). Reported oncological outcomes from historic trials generally underestimated contemporary outcomes.

Conclusions

Current and predicted rates for 3-year LRF and 5-year survivals are considerably improved compared with those in historic trials.
Targeting BRD/BET proteins inhibits adaptive kinome upregulation and enhances the effects of BRAF/MEK inhibitors in melanoma
Authors: Tiago Manoela , Capparelli Claudia , Erkes Dan A. , Purwin Timothy J. , Heilman Shea A. , Berger Adam C. , Davies Michael A. , Aplin Andrew E.
Published: January 2020

Background

BRAF-mutant melanoma patients respond to BRAF inhibitors and MEK inhibitors (BRAFi/MEKi), but drug-tolerant cells persist, which may seed disease progression. Adaptive activation of receptor tyrosine kinases (RTKs) has been associated with melanoma cell drug tolerance following targeted therapy. While co-targeting individual RTKs can enhance the efficacy of BRAFi/MEKi effects, it remains unclear how to broadly target multiple RTKs to achieve more durable tumour growth inhibition.

Methods

The blockage of adaptive RTK responses by the new BET inhibitor (BETi), PLX51107, was measured by RPPA and Western blot. Melanoma growth was evaluated in vitro by colony assay and EdU staining, as well as in skin reconstructs, xenografts and PDX models following BRAFi, MEKi and/or PLX51107 treatment.

Results

Treatment with PLX51107 limited BRAFi/MEKi upregulation of ErbB3 and PDGFR-β expression levels. Similar effects were observed following BRD2/4 depletion. In stage III melanoma patients, expression of BRD2/4 was strongly correlated with ErbB3. PLX51107 enhanced the effects of BRAFi/MEKi on inhibiting melanoma growth in vitro, in human skin reconstructs and in xenografts in vivo. Continuous triple drug combination treatment resulted in significant weight loss in mice, but intermittent BETi combined with continuous BRAFi/MEKi treatment was tolerable and improved durable tumour inhibition outcomes.

Conclusions

Together, our data suggest that intermittent inhibition of BET proteins may improve the duration of responses following BRAFi/MEKi treatment in BRAF-mutant melanoma.
Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations
Authors: Li Yun Rose , Glessner Joseph T. , Coe Bradley P. , Li Jin , Mohebnasab Maede , Chang Xiao , Connolly John , Kao Charlly , Wei Zhi , Bradfield Jonathan , Kim Cecilia , Hou Cuiping , Khan Munir , Mentch Frank , Qiu Haijun , Bakay Marina , Cardinale Christopher , Lemma Maria , Abrams Debra , Bridglall-Jhingoor Andrew , Behr Meckenzie , Harrison Shanell , Otieno George , Thomas Alexandria , Wang Fengxiang , Chiavacci Rosetta , Wu Lawrence , Hadley Dexter , Goldmuntz Elizabeth , Elia Josephine , Maris John , Grundmeier Robert , Devoto Marcella , Keating Brendan , March Michael , Pellagrino Renata , Grant Struan F. A. , Sleiman Patrick M. A. , Li Mingyao , Eichler Evan E. , Hakonarson Hakon
Published: January 2020

Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (P < 1 × 10−3). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.
STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment
Authors: Lohard Steven , Bourgeois Nathalie , Maillet Laurent , Gautier Fabien , Fétiveau Aurélie , Lasla Hamza , Nguyen Frédérique , Vuillier Céline , Dumont Alison , Moreau-Aubry Agnès , Frapin Morgane , David Laurent , Loussouarn Delphine , Kerdraon Olivier , Campone Mario , Jézéquel Pascal , Juin Philippe P. , Barillé-Nion Sophie
Published: January 2020

A fascinating but uncharacterized action of antimitotic chemotherapy is to collectively prime cancer cells to apoptotic mitochondrial outer membrane permeabilization (MOMP), while impacting only on cycling cell subsets. Here, we show that a proapoptotic secretory phenotype is induced by activation of cGAS/STING in cancer cells that are hit by antimitotic treatment, accumulate micronuclei and maintain mitochondrial integrity despite intrinsic apoptotic pressure. Organotypic cultures of primary human breast tumors and patient-derived xenografts sensitive to paclitaxel exhibit gene expression signatures typical of type I IFN and TNFα exposure. These cytokines induced by cGAS/STING activation trigger NOXA expression in neighboring cells and render them acutely sensitive to BCL-xL inhibition. cGAS/STING-dependent apoptotic effects are required for paclitaxel response in vivo, and they are amplified by sequential, but not synchronous, administration of BH3 mimetics. Thus anti-mitotic agents propagate apoptotic priming across heterogeneously sensitive cancer cells through cytosolic DNA sensing pathway-dependent extracellular signals, exploitable by delayed MOMP targeting.
Author Correction: Direct imaging of structural disordering and heterogeneous dynamics of fullerene molecular liquid
Authors: Choe Jeongheon , Lee Yangjin , Park Jungwon , Kim Yunho , Kim Chae Un , Kim Kwanpyo
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose–xylose co-substrate
Authors: Fujiwara Ryosuke , Noda Shuhei , Tanaka Tsutomu , Kondo Akihiko
Published: January 2020

Glucose and xylose are the major components of lignocellulose. Effective utilization of both sugars can improve the efficiency of bioproduction. Here, we report a method termed parallel metabolic pathway engineering (PMPE) for producing shikimate pathway derivatives from glucose–xylose co-substrate. In this method, we seek to use glucose mainly for target chemical production, and xylose for supplying essential metabolites for cell growth. Glycolysis and the pentose phosphate pathway are completely separated from the tricarboxylic acid (TCA) cycle. To recover cell growth, we introduce a xylose catabolic pathway that directly flows into the TCA cycle. As a result, we can produce 4.09 g L−1cis,cis-muconic acid using the PMPE Escherichia coli strain with high yield (0.31 g g−1 of glucose) and produce l-tyrosine with 64% of the theoretical yield. The PMPE strategy can contribute to the development of clean processes for producing various valuable chemicals from lignocellulosic resources.
Spin pumping during the antiferromagnetic–ferromagnetic phase transition of iron–rhodium
Authors: Wang Yuyan , Decker Martin M. , Meier Thomas N. G. , Chen Xianzhe , Song Cheng , Grünbaum Tobias , Zhao Weisheng , Zhang Junying , Chen Lin , Back Christian H.
Published: January 2020

FeRh attracts intensive interest in antiferromagnetic (AFM) spintronics due to its first-order phase transition between the AFM and ferromagnetic (FM) phase, which is unique for exploring spin dynamics in coexisting phases. Here, we report lateral spin pumping by which angular momentum is transferred from FM domains into the AFM matrix during the phase transition of ultrathin FeRh films. In addition, FeRh is verified to be both an efficient spin generator and an efficient spin sink, by electrically probing vertical spin pumping from FM-FeRh into Pt and from Py into FeRh, respectively. A dramatic enhancement of damping related to AFM-FeRh is observed during the phase transition, which we prove to be dominated by lateral spin pumping across the FM/AFM interface. The discovery of lateral spin pumping provides insight into the spin dynamics of magnetic thin films with mixed-phases, and the significantly modulated damping advances its potential applications, such as ultrafast spintronics.
Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy
Authors: Kwon Jiwoong , Park Jong-Seok , Kang Minsu , Choi Soobin , Park Jumi , Kim Gyeong Tae , Lee Changwook , Cha Sangwon , Rhee Hyun-Woo , Shim Sang-Hee
Published: January 2020

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging.
Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation
Authors: King Matthew R. , Petry Sabine
Published: January 2020

Phase separation of substrates and effectors is proposed to enhance biological reaction rates and efficiency. Targeting protein for Xklp2 (TPX2) is an effector of branching microtubule nucleation in spindles and functions with the substrate tubulin by an unknown mechanism. Here we show that TPX2 phase separates into a co-condensate with tubulin, which mediates microtubule nucleation in vitro and in isolated cytosol. TPX2-tubulin co-condensation preferentially occurs on pre-existing microtubules, the site of branching microtubule nucleation, at the endogenous and physiologically relevant concentration of TPX2. Truncation and chimera versions of TPX2 suggest that TPX2-tubulin co-condensation enhances the efficiency of TPX2-mediated branching microtubule nucleation. Finally, the known inhibitor of TPX2, the importin-α/β heterodimer, regulates TPX2 condensation in vitro and, consequently, branching microtubule nucleation activity in isolated cytosol. Our study demonstrates how regulated phase separation can simultaneously enhance reaction efficiency and spatially coordinate microtubule nucleation, which may facilitate rapid and accurate spindle formation.
Gold endowments of porphyry deposits controlled by precipitation efficiency
Authors: Chiaradia Massimo
Published: January 2020

Porphyry deposits are natural suppliers of most copper and significant gold to our society. Whereas the Cu-richest (Au-poor) porphyries are related to Andean-type subduction and typical calc-alkaline magmatism, the Au-richest porphyries are associated with high-K calc-alkaline to alkaline magmatism in late to post-subduction or post-collision and extensional settings, and subordinately with calc-alkaline magmatism. The reasons behind these associations and the large variations in metal endowments of porphyry Cu–Au deposits remain obscure. Here, I show that porphyry Cu–Au deposits define two distinct trends in Au vs. Cu tonnage plots (Cu-rich and Au-rich). Metal endowments for both trends grow larger the longer the mineralization process. However, Au is precipitated at much higher rates in Au-rich than in Cu-rich porphyry deposits. Using Monte Carlo simulations of petrologic processes, I show that whereas Cu-rich porphyries require large amounts of magma and water to be formed, Au-rich porphyries are the result of a better efficiency of Au precipitation.
A mosquito salivary protein promotes flavivirus transmission by activation of autophagy
Authors: Sun Peng , Nie Kaixiao , Zhu Yibin , Liu Yang , Wu Pa , Liu Ziwen , Du Senyan , Fan Huahao , Chen Chun-Hong , Zhang Renli , Wang Penghua , Cheng Gong
Published: January 2020

Transmission from an infected mosquito to a host is an essential process in the life cycle of mosquito-borne flaviviruses. Numerous studies have demonstrated that mosquito saliva facilitates viral transmission. Here we find that a saliva-specific protein, named Aedes aegypti venom allergen-1 (AaVA-1), promotes dengue and Zika virus transmission by activating autophagy in host immune cells of the monocyte lineage. The AG6 mice (ifnar1–/–ifngr1–/–) bitten by the virus-infected AaVA-1-deficient mosquitoes present a lower viremia and prolonged survival. AaVA-1 intracellularly interacts with a dominant negative binder of Beclin-1, known as leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), and releases Beclin-1 from LRPPRC-mediated sequestration, thereby enabling the initialization of downstream autophagic signaling. A deficiency in Beclin-1 reduces viral infection in mice and abolishes AaVA-1-mediated enhancement of ZIKV transmission by mosquitoes. Our study provides a mechanistic insight into saliva-aided viral transmission and could offer a potential prophylactic target for reducing flavivirus transmission.
Cysteine-encoded chirality evolution in plasmonic rhombic dodecahedral gold nanoparticles
Authors: Lee Hye-Eun , Kim Ryeong Myeong , Ahn Hyo-Yong , Lee Yoon Young , Byun Gi Hyun , Im Sang Won , Mun Jungho , Rho Junsuk , Nam Ki Tae
Published: January 2020

Chiral plasmonic nanostructures have opened up unprecedented opportunities in optical applications. We present chirality evolution in nanoparticles focusing on the crystallographic aspects and elucidate key parameters for chiral structure formation. From a detailed understanding of chirality formation, we achieved a morphology (432 Helicoid IV) of three-dimensionally controlled chiral plasmonic nanoparticles based on the rhombic dodecahedral shape. The role of the synthesis parameters, seed, cysteine, cetyltrimethylammonium bromide and ascorbic acid on chiral formation are studied, and based on this understanding, the systematic control of the chiral structure is presented. The relation between the modulated chiral structure factors and optical response is further elucidated by electromagnetic simulation. Importantly, a new optical response is achieved by assembling chiral nanoparticles into a film. This comprehensive study of chiral nanoparticles will provide valuable insight for the further development of diverse chiral plasmonic nanostructures with fascinating properties.
Sensitive detection of a bacterial pathogen using allosteric probe-initiated catalysis and CRISPR-Cas13a amplification reaction
Authors: Shen Jinjin , Zhou Xiaoming , Shan Yuanyue , Yue Huahua , Huang Ru , Hu Jiaming , Xing Da
Published: January 2020

The ability to detect low numbers of microbial cells in food and clinical samples is highly valuable but remains a challenge. Here we present a detection system (called ‘APC-Cas’) that can detect very low numbers of a bacterial pathogen without isolation, using a three-stage amplification to generate powerful fluorescence signals. APC-Cas involves a combination of nucleic acid-based allosteric probes and CRISPR-Cas13a components. It can selectively and sensitively quantify Salmonella Enteritidis cells (from 1 to 105 CFU) in various types of samples such as milk, showing similar or higher sensitivity and accuracy compared with conventional real-time PCR. Furthermore, APC-Cas can identify low numbers of S. Enteritidis cells in mouse serum, distinguishing mice with early- and late-stage infection from uninfected mice. Our method may have potential clinical applications for early diagnosis of pathogens.
Efficient electrochemical production of glucaric acid and H2 via glucose electrolysis
Authors: Liu Wu-Jun , Xu Zhuoran , Zhao Dongting , Pan Xiao-Qiang , Li Hong-Chao , Hu Xiao , Fan Zhi-Yong , Wang Wei-Kang , Zhao Guo-Hua , Jin Song , Huber George W. , Yu Han-Qing
Published: January 2020

Glucose electrolysis offers a prospect of value-added glucaric acid synthesis and energy-saving hydrogen production from the biomass-based platform molecules. Here we report that nanostructured NiFe oxide (NiFeOx) and nitride (NiFeNx) catalysts, synthesized from NiFe layered double hydroxide nanosheet arrays on three-dimensional Ni foams, demonstrate a high activity and selectivity towards anodic glucose oxidation. The electrolytic cell assembled with these two catalysts can deliver 100 mA cm−2 at 1.39 V. A faradaic efficiency of 87% and glucaric acid yield of 83% are obtained from the glucose electrolysis, which takes place via a guluronic acid pathway evidenced by in-situ infrared spectroscopy. A rigorous process model combined with a techno-economic analysis shows that the electrochemical reduction of glucose produces glucaric acid at a 54% lower cost than the current chemical approach. This work suggests that glucose electrolysis is an energy-saving and cost-effective approach for H2 production and biomass valorization.
A bioinspired analogous nerve towards artificial intelligence
Authors: Liao Xinqin , Song Weitao , Zhang Xiangyu , Yan Chaoqun , Li Tianliang , Ren Hongliang , Liu Cunzhi , Wang Yongtian , Zheng Yuanjin
Published: January 2020

A bionic artificial device commonly integrates various distributed functional units to mimic the functions of biological sensory neural system, bringing intricate interconnections, complicated structure, and interference in signal transmission. Here we show an all-in-one bionic artificial nerve based on a separate electrical double-layers structure that integrates the functions of perception, recognition, and transmission. The bionic artificial nerve features flexibility, rapid response (<21 ms), high robustness, excellent durability (>10,000 tests), personalized cutability, and no energy consumption when no mechanical stimulation is being applied. The response signals are highly regionally differentiated for the mechanical stimulations, which enables the bionic artificial nerve to mimic the spatiotemporally dynamic logic of a biological neural network. Multifunctional touch interactions demonstrate the enormous potential of the bionic artificial nerve for human-machine hybrid perceptual enhancement. By incorporating the spatiotemporal resolution function and algorithmic analysis, we hope that bionic artificial nerves will promote further development of sophisticated neuroprosthetics and intelligent robotics.
Global optimization of quantum dynamics with AlphaZero deep exploration
Authors: Dalgaard Mogens , Motzoi Felix , Sørensen Jens Jakob , Sherson Jacob
Published: January 2020

While a large number of algorithms for optimizing quantum dynamics for different objectives have been developed, a common limitation is the reliance on good initial guesses, being either random or based on heuristics and intuitions. Here we implement a tabula rasa deep quantum exploration version of the Deepmind AlphaZero algorithm for systematically averting this limitation. AlphaZero employs a deep neural network in conjunction with deep lookahead in a guided tree search, which allows for predictive hidden-variable approximation of the quantum parameter landscape. To emphasize transferability, we apply and benchmark the algorithm on three classes of control problems using only a single common set of algorithmic hyperparameters. AlphaZero achieves substantial improvements in both the quality and quantity of good solution clusters compared to earlier methods. It is able to spontaneously learn unexpected hidden structure and global symmetry in the solutions, going beyond even human heuristics.
Deep learning, computer-aided radiography reading for tuberculosis: a diagnostic accuracy study from a tertiary hospital in India
Authors: Nash Madlen , Kadavigere Rajagopal , Andrade Jasbon , Sukumar Cynthia Amrutha , Chawla Kiran , Shenoy Vishnu Prasad , Pande Tripti , Huddart Sophie , Pai Madhukar , Saravu Kavitha
Published: January 2020

In general, chest radiographs (CXR) have high sensitivity and moderate specificity for active pulmonary tuberculosis (PTB) screening when interpreted by human readers. However, they are challenging to scale due to hardware costs and the dearth of professionals available to interpret CXR in low-resource, high PTB burden settings. Recently, several computer-aided detection (CAD) programs have been developed to facilitate automated CXR interpretation. We conducted a retrospective case-control study to assess the diagnostic accuracy of a CAD software (qXR, Qure.ai, Mumbai, India) using microbiologically-confirmed PTB as the reference standard. To assess overall accuracy of qXR, receiver operating characteristic (ROC) analysis was used to determine the area under the curve (AUC), along with 95% confidence intervals (CI). Kappa coefficients, and associated 95% CI, were used to investigate inter-rater reliability of the radiologists for detection of specific chest abnormalities. In total, 317 cases and 612 controls were included in the analysis. The AUC for qXR for the detection of microbiologically-confirmed PTB was 0.81 (95% CI: 0.78, 0.84). Using the threshold that maximized sensitivity and specificity of qXR simultaneously, the software achieved a sensitivity and specificity of 71% (95% CI: 66%, 76%) and 80% (95% CI: 77%, 83%), respectively. The sensitivity and specificity of radiologists for the detection of microbiologically-confirmed PTB was 56% (95% CI: 50%, 62%) and 80% (95% CI: 77%, 83%), respectively. For detection of key PTB-related abnormalities ‘pleural effusion’ and ‘cavity’, qXR achieved an AUC of 0.94 (95% CI: 0.92, 0.96) and 0.84 (95% CI: 0.82, 0.87), respectively. For the other abnormalities, the AUC ranged from 0.75 (95% CI: 0.70, 0.80) to 0.94 (95% CI: 0.91, 0.96). The controls had a high prevalence of other lung diseases which can cause radiological manifestations similar to PTB (e.g., 26% had pneumonia, 15% had lung malignancy, etc.). In a tertiary hospital in India, qXR demonstrated moderate sensitivity and specificity for the detection of PTB. There is likely a larger role for CAD software as a triage test for PTB at the primary care level in settings where access to radiologists in limited. Larger prospective studies that can better assess heterogeneity in important subgroups are needed.
Troponin destabilization impairs sarcomere-cytoskeleton interactions in iPSC-derived cardiomyocytes from dilated cardiomyopathy patients
Authors: Dai Yuanyuan , Amenov Asset , Ignatyeva Nadezda , Koschinski Andreas , Xu Hang , Soong Poh Loong , Tiburcy Malte , Linke Wolfgang A. , Zaccolo Manuela , Hasenfuss Gerd , Zimmermann Wolfram-Hubertus , Ebert Antje
Published: January 2020

The sarcomeric troponin-tropomyosin complex is a critical mediator of excitation-contraction coupling, sarcomeric stability and force generation. We previously reported that induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from patients with a dilated cardiomyopathy (DCM) mutation, troponin T (TnT)-R173W, display sarcomere protein misalignment and impaired contractility. Yet it is not known how TnT mutation causes dysfunction of sarcomere microdomains and how these events contribute to misalignment of sarcomeric proteins in presence of DCM TnT-R173W. Using a human iPSC-CM model combined with CRISPR/Cas9-engineered isogenic controls, we uncovered that TnT-R173W destabilizes molecular interactions of troponin with tropomyosin, and limits binding of PKA to local sarcomere microdomains. This attenuates troponin phosphorylation and dysregulates local sarcomeric microdomains in DCM iPSC-CMs. Disrupted microdomain signaling impairs MYH7-mediated, AMPK-dependent sarcomere-cytoskeleton filament interactions and plasma membrane attachment. Small molecule-based activation of AMPK can restore TnT microdomain interactions, and partially recovers sarcomere protein misalignment as well as impaired contractility in DCM TnT-R173W iPSC-CMs. Our findings suggest a novel therapeutic direction targeting sarcomere- cytoskeleton interactions to induce sarcomere re-organization and contractile recovery in DCM.