bluuebunny/crossref_metadata_2025 huggingface dataset:
Understand the cogs to understand cognition
Authors: Marblestone Adam H. , Wayne Greg , Kording Konrad P.
Published: November 2017

Lake et al. suggest that current AI systems lack the inductive biases that enable human learning. However, Lake et al.'s proposed biases may not directly map onto mechanisms in the developing brain. A convergence of fields may soon create a correspondence between biological neural circuits and optimization in structured architectures, allowing us to systematically dissect how brains learn.
Structural priming can inform syntactic analyses of partially grammaticalized constructions
Authors: Francis Elaine J.
Published: November 2017

Branigan & Pickering (B&P) argue successfully that structural priming provides valuable information for developing psychologically plausible syntactic and semantic theories. I discuss how their approach can be used to help determine whether partially grammaticalized constructions that have undergone semantic change also have undergone syntactic reanalysis. I then consider cases in which evidence from priming cannot distinguish between competing syntactic analyses.
Structural priming supports grammatical networks
Authors: Hudson Richard
Published: November 2017

As Branigan & Pickering (B&P) argue, structural priming has important implications for the theory of language structure, but these implications go beyond those suggested. Priming implies a network structure, so the grammar must be a network and so must sentence structure. Instead of phrase structure, the most promising model for syntactic structure is enriched dependency structure, as in Word Grammar.
Structural priming is a useful but imperfect technique for studying all linguistic representations, including those of pragmatics
Authors: Rees Alice , Bott Lewis
Published: November 2017

Structural priming is a useful tool for investigating linguistics representations. We argue that structural priming can be extended to the investigation of pragmatic representations such as Gricean enrichments. That is not to say priming is without its limitations, however. Interpreting a failure to observe priming may not be as simple as Branigan & Pickering (B&P) imply.
The relationship between priming and linguistic representations is mediated by processing constraints
Authors: Slevc L. Robert , Ivanova Iva
Published: November 2017

Understanding the nature of linguistic representations undoubtedly will benefit from multiple types of evidence, including structural priming. Here, we argue that successfully gaining linguistic insights from structural priming requires us to better understand (1) the precise mappings between linguistic input and comprehenders' syntactic knowledge; and (2) the role of cognitive faculties such as memory and attention in structural priming.
Ingredients of intelligence: From classic debates to an engineering roadmap
Authors: Lake Brenden M. , Ullman Tomer D. , Tenenbaum Joshua B. , Gershman Samuel J.
Published: November 2017

We were encouraged by the broad enthusiasm for building machines that learn and think in more human-like ways. Many commentators saw our set of key ingredients as helpful, but there was disagreement regarding the origin and structure of those ingredients. Our response covers three main dimensions of this disagreement: nature versus nurture, coherent theories versus theory fragments, and symbolic versus sub-symbolic representations. These dimensions align with classic debates in artificial intelligence and cognitive science, although, rather than embracing these debates, we emphasize ways of moving beyond them. Several commentators saw our set of key ingredients as incomplete and offered a wide range of additions. We agree that these additional ingredients are important in the long run and discuss prospects for incorporating them. Finally, we consider some of the ethical questions raised regarding the research program as a whole.
Does EU support contribute to economically successful Public-Private Partnerships (PPPs)? A panel data analysis of road PPP projects in Spain
Authors: Garrido Laura , Rangel Thais , Baeza María De Los Ángeles , Vassallo José M.
Published: November 2017

The EU infrastructure policy has relied on Public-Private Partnerships (PPPs) as a means to successfully deliver infrastructure of benefit for the EU. To reach its infrastructure policy objectives, the EU has implemented support mechanisms aimed at facilitating the delivery of PPPs. This article is aimed at evaluating to what extent these mechanisms have actually contributed to improving the economic performance of PPPs. To that end, we have selected the case of Spanish road PPPs for empirical analysis. The main result shows that EU support positively influences the economic performance of PPP projects. This is caused by the fact that the EU conditions its financial support on a project’s meeting a set of requirements that help assure the success of the project. From this result, we obtain a set of conclusions that may be generalised to other cases, and provide a contribution to the body of knowledge on PPPs.
USING THE INTEGRATE-HTA GUIDANCE: EXPERIENCE FROM CADTH
Authors: Bond Ken , Weeks Laura
Published: November 2017

Objectives:The aim of this study was to describe an initial exploration by CADTH, Canada's pan-Canadian health technology assessment (HTA) agency, in using the INTEGRATE-HTA guidance in the production of an HTA that examined the use of both in-center and in-home dialysis modalities for the treatment of end-stage kidney disease in adults in Canada.

Methods and Results:We outline CADTH's standard HTA production process and context and then describe the experience of the assessment team in using the INTEGRATE-HTA guidance, specifically to help structure and guide the use of a logic model, the identification of implementation issues, and the identification and examination of ethical issues. For each of the aspects, we describe and reflect on how the assessment team used the guidance, challenges that were encountered in its use, and whether and how we might address these challenges when using the INTEGRATE-HTA guidance in the future.

Conclusions:INTEGRATE-HTA provided detailed and helpful guidance for truly integrating wide-ranging aspects of HTA. Our agency was challenged by a steep learning curve for assessment team members, tight project timelines, and a misalignment of current HTA processes with those required to implement the guidance. Nevertheless, using the guidance initiated a dialogue about what might be needed to assess complex interventions and the potential process changes that could facilitate conducting more integrated assessments.
Seasonality in abundance and detection bias of birds in a tropical dry forest in north-eastern South America
Authors: de Oliveira e Silva Clarisse Caroline , Pichorim Mauro , de Moura Pedro Teófilo Silva , França Leonardo Fernandes
Published: November 2017

Seasonal fluctuations in bird abundance are expected in semi-arid environments, but estimates may be biased if detectability is not considered. In a tropical dry forest in north-eastern Brazil, we evaluated whether bird abundance is highly seasonal, and associated with time-specific variability in detectability. We mark-recaptured birds with mist nets over three field visits (3487 records from 75 species), and used closed-capture models to estimate detectability and abundance in birds divided into three groups (all, residents, insectivores). In the two dry periods, the best models resulted in capture estimates at least three times larger than recapture, and both estimates were twice that of when rains occurred on the day preceding sampling. Abundance varied between dry and wet periods from 4.0 (from 115 ± 34 to 479 ± 144) to 13 times (183 ± 8 to 2463 ± 351). Estimates were 1.5–3.2 times greater in the dry period when behavioural responses of birds were excluded from capture-recapture models. Meanwhile, in the wet period the relative abundance was between 33–76% smaller than best-fit models estimated. This study found variation in avian abundance greater than that observed in other Neotropical dry forests, and indicates that biases may be common when not including detectability.
Gastric lymphoma: association withHelicobacter pyloriouter membrane protein Q (HopQ) and cytotoxic-pathogenicity activity island (CPAI) genes
Authors: YAKOOB J. , ABBAS Z. , AHMAD Z. , TARIQ K. , AWAN S. , MUSTAFA K. , KHAN R.
Published: November 2017

B-cell non-Hodgkin lymphoma (B-cell NHL) is the second commonest malignancy in the stomach. We determined the distribution ofHelicobacter pyloriouter membrane protein Q (HopQ) allelic type, cytotoxin-associated gene (cag)-pathogenicity activity island (cag-PAI) and vacuolation activating cytotoxin A (vacA) genes, respectively, in patients with B-cell NHL. We also compared them with their distribution in non-ulcer dyspepsia (NUD).H. pyloriwas cultured from gastric biopsy tissue obtained at endoscopy. Polymerase chain reaction was performed. Of 170 patients enrolled, 114 (63%) had NUD and 56 (37%) had B-cell NHL. HopQ type 1 was positive in 66 (58%) in NUD compared with 46 (82%) (P= 0·002) in B-cell NHL; HopQ type 2 was positive in 93 (82%) with NUD compared with 56 (100%) (P< 0·001) in B-cell NHL. Multiple HopQ types were present in 46 (40%) in NUD compared with 46 (82%) (P< 0·001) in B-cell NHL. CagA was positive in 48 (42%) in NUDvs. 50 (89%) (P< 0·001) in B-cell NHL; cagT was positive in 35 (31%) in NUDvs. 45 (80%) (P< 0·001) in B-cell NHL; left end of thecagAgene (LEC)1 was positive in 23 (20%) in NUDvs. 43 (77%) (P< 0·001) in B-cell NHL. VacAs1am1 positive in B-cell NHL in 48 (86%) (P< 0·001)vs. 50 (44%) in NUD, while s1am2 was positive in 20 (17%) in NUDvs. 46 (82%) (P< 0·001) in B-cell NHL.H. pyloristrains with multiple HopQ allelic types, truncated cag-PAI evidenced by expression of cagA, cagT and cag LEC with virulent vacAs1 alleles are associated with B-cell NHL development.
Bidirectional associations between body dissatisfaction and depressive symptoms from adolescence through early adulthood
Authors: Sharpe Helen , Patalay Praveetha , Choo Tse-Hwei , Wall Melanie , Mason Susan M. , Goldschmidt Andrea B. , Neumark-Sztainer Dianne
Published: November 2017

Body dissatisfaction and depressive symptoms are commonly experienced during adolescence and increase the risk of adverse health outcomes, especially eating disorders. However, the dominant temporal associations between these two experiences (i.e., whether one is a risk factor for the other or the two are mutually reinforcing) has yet to be fully explored. We examined the associations between body dissatisfaction and depressive symptoms assessed at baseline and 5- and 10-year follow-up in younger (M age = 12.9 years at baseline, 56% female, n = 577) and older (M age = 15.9 years at baseline, 57% female, n = 1,325) adolescent cohorts assessed as part of Project Eating Among Teens and Young Adults. Associations between body dissatisfaction and depressive symptoms were examined using cross-lagged models. For females, the dominant directionality was for body dissatisfaction predicting later depressive symptoms. For males, the picture was more complex, with developmentally sensitive associations in which depressive symptoms predicted later body dissatisfaction in early adolescence and early adulthood, but the reverse association was dominant during middle adolescence. These findings suggest that interventions should be tailored to dynamic risk profiles that shift over adolescence and early adulthood, and that targeting body dissatisfaction at key periods during development may have downstream impacts on depressive symptoms.
Child language and parenting antecedents and externalizing outcomes of emotion regulation pathways across early childhood: A person-centered approach
Authors: Bendezú Jason José , Cole Pamela M. , Tan Patricia Z. , Armstrong Laura Marie , Reitz Elizabeth B. , Wolf Rachel M.
Published: November 2017

Decreases in children's anger reactivity because of the onset of their autonomous use of strategies characterizes the prevailing model of the development of emotion regulation in early childhood (Kopp, 1989). There is, however, limited evidence of the varied pathways that mark this development and their proposed antecedents and consequences. This study used a person-centered approach to identify such pathways, antecedents, and outcomes. A sample of 120 children from economically strained rural and semirural households were observed while waiting to open a gift at ages 24, 36, and 48 months. Multitrajectory modeling of children's anger expressions and strategy use yielded three subgroups. As they aged, typically developing children's strategy use (calm bids and focused distraction) increased while anger expressions decreased. Later developing children, though initially elevated in anger expression and low in strategy use, demonstrated marked growth across indicators and did not differ from typically developing children at 48 months. At-risk children, despite developing calm bidding skills, did not display longitudinal self-distraction increases or anger expression declines. Some predicted antecedents (12–24 month child language skills and language-capitalizing parenting practices) and outcomes (age 5 years externalizing behavior) differentiated pathways. Findings illustrate how indicator-specific departures from typical pathways signal risk for behavior problems and point to pathway-specific intervention opportunities.
A NEW SPECIES OF PARABOEA (GESNERIACEAE) FROM THAILAND
Authors: Puglisi C. , Phutthai T.
Published: November 2017

A new species of Paraboea, P. fimbriata C.Puglisi & Phutthai, from Sai Yok District, Kanchanaburi Province, Thailand, is described.
Health claims and product endorsements on child-oriented beverages in Guatemala
Authors: Perry Andrew , Chacon Violeta , Barnoya Joaquin
Published: November 2017

Objective

We sought to describe front-of-package marketing strategies and nutritional quality of child-oriented beverages in Guatemala.

Design

We purchased all child-oriented ready-to-drink fruit drinks, milks and carbonated beverages in three convenience stores and one supermarket in Guatemala City. Front-of-package marketing was defined as the presence of spokes-characters, cartoons, celebrities, or health-related images, words, claims or endorsements on beverage packaging. We used the UK Nutrition Profiling Model (NPM) to classify beverages as healthy or less healthy.

Setting

Guatemala City, Guatemala.

Results

We purchased eighty-nine beverages; most were fruit drinks (n52, 58 %), milk (15, 17 %), carbonated beverages (5, 17 %), rice/soya products (5, 6·0 %), water (1, 1 %) and energy drinks (1, 1 %). Two-thirds (57, 64 %) had health claims. Of those with a nutrition facts label (85, 96 %), nearly all (76, 89 %) were classified as less healthy. No association between the presence of health claims and NPM score (P=0·26) was found. Eight beverages had health-related endorsements. However, only one beverage was classified as healthy.

Conclusions

In this sample of beverages in Guatemala City, health claims and health-related endorsements are used to promote beverages with poor nutritional quality. Our data support evidence-based policies to regulate the use of front-of-package health claims and endorsements based on nutritional quality.
Cryo-Scanning Electron Microscopy (SEM) and Scanning Transmission Electron Microscopy (STEM)-in-SEM for Bio- and Organo-Mineral Interface Characterization in the Environment
Authors: Wille Guillaume , Hellal Jennifer , Ollivier Patrick , Richard Annie , Burel Agnes , Jolly Louis , Crampon Marc , Michel Caroline
Published: November 2017

Understanding biofilm interactions with surrounding substratum and pollutants/particles can benefit from the application of existing microscopy tools. Using the example of biofilm interactions with zero-valent iron nanoparticles (nZVI), this study aims to apply various approaches in biofilm preparation and labeling for fluorescent or electron microscopy and energy dispersive X-ray spectrometry (EDS) microanalysis for accurate observations. According to the targeted microscopy method, biofilms were sampled as flocs or attached biofilm, submitted to labeling using 4’,6-diamidino-2-phenylindol, lectins PNA and ConA coupled to fluorescent dye or gold nanoparticles, and prepared for observation (fixation, cross-section, freezing, ultramicrotomy). Fluorescent microscopy revealed that nZVI were embedded in the biofilm structure as aggregates but the resolution was insufficient to observe individual nZVI. Cryo-scanning electron microscopy (SEM) observations showed nZVI aggregates close to bacteria, but it was not possible to confirm direct interactions between nZVI and cell membranes. Scanning transmission electron microscopy in the SEM (STEM-in-SEM) showed that nZVI aggregates could enter the biofilm to a depth of 7–11µm. Bacteria were surrounded by a ring of extracellular polymeric substances (EPS) preventing direct nZVI/membrane interactions. STEM/EDS mapping revealed a co-localization of nZVI aggregates with lectins suggesting a potential role of EPS in nZVI embedding. Thus, the combination of divergent microscopy approaches is a good approach to better understand and characterize biofilm/metal interactions.
From Quaker Oats to Virgin Brides: Brand capital as a complex adaptive system
Authors: HARPER DAVID A. , ENDRES ANTHONY M.
Published: November 2017

We examine brand building from the perspective of complex adaptive systems. Brand building is a neglected engine of capital formation, innovation and institutional change in market economies. The nature of brands and the service streams they generate have been construed too narrowly. Brands are capital: entrepreneurs use brands as market-making devices that create value and capture profit, while consumers use brands to derive psychic income and lifestyle benefits. Brands are building blocks that can be combined in production to fill perceived gaps in brand architectures and capital structures. These structures are themselves complex adaptive systems. In an era of digital technological platforms, complex generative networks are the institutional locus of brand creation and brand extensions. Innovation in brand building is a socially distributed, service-intensive and interpretive process; it entails combinatorial experiments in resource integration by heterogeneous and socially connected actors, such as entrepreneur-producers, end-users and distributors. Legal brand owners never have total control over their brands – customer networks often exercise substantial de facto control rights (economic property rights) over the use and transformation of brands. Both the entire branding system (as a form of organization) and individual iconic brands can crystallize into relatively stable institutions that orient and coordinate market behaviour.
Food insecurity among people with severe mental disorder in a rural Ethiopian setting: a comparative, population-based study
Authors: Tirfessa K. , Lund C. , Medhin G. , Hailemichael Y. , Fekadu A. , Hanlon C.
Published: November 2017

Aim.

In low-income African countries, ensuring food security for all segments of the population is a high priority. Mental illness is associated consistently with poverty, but there is little evidence regarding the association with food insecurity. The aim of this study was to compare the levels of food insecurity in people with severe mental disorders (SMD) with the general population in a rural African setting with a high burden of food insecurity.

Method.

Households of 292 community-ascertained people with a specialist-confirmed diagnosis of SMD (including schizophrenia and bipolar disorder) were compared with 284 households without a person with SMD in a rural district in south Ethiopia. At the time of the study, no mental health services were available within the district. Food insecurity was measured using a validated version of the Household Food Insecurity Access Scale. Disability was measured using the World Health Organisation Disability Assessment Schedule 2.0.

Result.

Severe household food insecurity was reported by 32.5% of people with SMD and 15.9% of respondents from comparison households: adjusted odds ratio 2.82 (95% confidence interval 1.62 to 4.91). Higher annual income was associated independently with lower odds of severe food insecurity. When total disability scores were added into the model, the association between SMD and food insecurity became non-significant, indicating a possible mediating role of disability.

Conclusion.

Efforts to alleviate food insecurity need to target people with SMD as a vulnerable group. Addressing the disabling effects of SMD would also be expected to reduce food insecurity. Access to mental health care integrated into primary care is being expanded in this district as part of the Programme for Improving Mental health carE (PRIME). The impact of treatment on disability and food insecurity will be evaluated.
Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release
Authors: Leloup Nadia , Lössl Philip , Meijer Dimphna H. , Brennich Martha , Heck Albert J. R. , Thies-Weesie Dominique M. E. , Janssen Bert J. C.
Published: November 2017

Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors.
Author Correction: Two-magnon scattering in the 5d all-in-all-out pyrochlore magnet Cd2Os2O7
Authors: Nguyen Thi Minh Hien , Sandilands Luke J. , Sohn C. H. , Kim C. H. , Wysocki Aleksander L. , Yang In-Sang , Moon S. J. , Ko Jae-Hyeon , Yamaura J. , Hiroi Z. , Noh Tae Won
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this article.
Cross continental increase in methane ebullition under climate change
Authors: Aben Ralf C. H. , Barros Nathan , van Donk Ellen , Frenken Thijs , Hilt Sabine , Kazanjian Garabet , Lamers Leon P. M. , Peeters Edwin T. H. M. , Roelofs Jan G. M. , de Senerpont Domis Lisette N. , Stephan Susanne , Velthuis Mandy , Van de Waal Dedmer B. , Wik Martin , Thornton Brett F. , Wilkinson Jeremy , DelSontro Tonya , Kosten Sarian
Published: November 2017

Methane (CH4) strongly contributes to observed global warming. As natural CH4 emissions mainly originate from wet ecosystems, it is important to unravel how climate change may affect these emissions. This is especially true for ebullition (bubble flux from sediments), a pathway that has long been underestimated but generally dominates emissions. Here we show a remarkably strong relationship between CH4 ebullition and temperature across a wide range of freshwater ecosystems on different continents using multi-seasonal CH4 ebullition data from the literature. As these temperature–ebullition relationships may have been affected by seasonal variation in organic matter availability, we also conducted a controlled year-round mesocosm experiment. Here 4 °C warming led to 51% higher total annual CH4 ebullition, while diffusion was not affected. Our combined findings suggest that global warming will strongly enhance freshwater CH4 emissions through a disproportional increase in ebullition (6–20% per 1 °C increase), contributing to global warming.
Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome
Authors: Thorsen Kasper , Dam Vibeke S. , Kjaer-Sorensen Kasper , Pedersen Lisbeth N. , Skeberdis V. Arvydas , Jurevičius Jonas , Treinys Rimantas , Petersen Ida M. B. S. , Nielsen Morten S. , Oxvig Claus , Morth J. Preben , Matchkov Vladimir V. , Aalkjær Christian , Bundgaard Henning , Jensen Henrik K.
Published: November 2017

Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl−]i shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.
Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival
Authors: Segatto Marco , Fittipaldi Raffaella , Pin Fabrizio , Sartori Roberta , Dae Ko Kyung , Zare Hossein , Fenizia Claudio , Zanchettin Gianpietro , Pierobon Elisa Sefora , Hatakeyama Shinji , Sperti Cosimo , Merigliano Stefano , Sandri Marco , Filippakopoulos Panagis , Costelli Paola , Sartorelli Vittorio , Caretti Giuseppina
Published: November 2017

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.
Short-term reward experience biases inference despite dissociable neural correlates
Authors: Fischer Adrian G. , Bourgeois-Gironde Sacha , Ullsperger Markus
Published: November 2017

Optimal decision-making employs short-term rewards and abstract long-term information based on which of these is deemed relevant. Employing short- vs. long-term information is associated with different learning mechanisms, yet neural evidence showing that these two are dissociable is lacking. Here we demonstrate that long-term, inference-based beliefs are biased by short-term reward experiences and that dissociable brain regions facilitate both types of learning. Long-term inferences are associated with dorsal striatal and frontopolar cortex activity, while short-term rewards engage the ventral striatum. Stronger concurrent representation of reward signals by mediodorsal striatum and frontopolar cortex correlates with less biased, more optimal individual long-term inference. Moreover, dynamic modulation of activity in a cortical cognitive control network and the medial striatum is associated with trial-by-trial control of biases in belief updating. This suggests that counteracting the processing of optimally to-be-ignored short-term rewards and cortical suppression of associated reward-signals, determines long-term learning success and failure.
Molecular basis of AKAP79 regulation by calmodulin
Authors: Patel Neha , Stengel Florian , Aebersold Ruedi , Gold Matthew G.
Published: November 2017

AKAP79/150 is essential for coordinating second messenger-responsive enzymes in processes including synaptic long-term depression. Ca2+ directly regulates AKAP79 through its effector calmodulin (CaM), but the molecular basis of this regulation was previously unknown. Here, we report that CaM recognizes a ‘1-4-7-8’ pattern of hydrophobic amino acids starting at Trp79 in AKAP79. Cross-linking coupled to mass spectrometry assisted mapping of the interaction site. Removal of the CaM-binding sequence in AKAP79 prevents formation of a Ca2+-sensitive interface between AKAP79 and calcineurin, and increases resting cellular PKA phosphorylation. We determined a crystal structure of CaM bound to a peptide encompassing its binding site in AKAP79. CaM adopts a highly compact conformation in which its open Ca2+-activated C-lobe and closed N-lobe cooperate to recognize a mixed α/310 helix in AKAP79. The structure guided a bioinformatic screen to identify potential sites in other proteins that may employ similar motifs for interaction with CaM.
Structural insights into the committed step of bacterial phospholipid biosynthesis
Authors: Li Zhenjian , Tang Yannan , Wu Yiran , Zhao Suwen , Bao Juan , Luo Yitian , Li Dianfan
Published: November 2017

The membrane-integral glycerol 3-phosphate (G3P) acyltransferase PlsY catalyses the committed and essential step in bacterial phospholipid biosynthesis by acylation of G3P, forming lysophosphatidic acid. It contains no known acyltransferase motifs, lacks eukaryotic homologs, and uses the unusual acyl-phosphate as acyl donor, as opposed to acyl-CoA or acyl-carrier protein for other acyltransferases. Previous studies have identified several PlsY inhibitors as potential antimicrobials. Here we determine the crystal structure of PlsY at 1.48 Å resolution, revealing a seven-transmembrane helix fold. Four additional substrate- and product-bound structures uncover the atomic details of its relatively inflexible active site. Structure and mutagenesis suggest a different acylation mechanism of ‘substrate-assisted catalysis’ that, unlike other acyltransferases, does not require a proteinaceous catalytic base to complete. The structure data and a high-throughput enzymatic assay developed in this work should prove useful for virtual and experimental screening of inhibitors against this vital bacterial enzyme.
Carrageenan catabolism is encoded by a complex regulon in marine heterotrophic bacteria
Authors: Ficko-Blean Elizabeth , Préchoux Aurélie , Thomas François , Rochat Tatiana , Larocque Robert , Zhu Yongtao , Stam Mark , Génicot Sabine , Jam Murielle , Calteau Alexandra , Viart Benjamin , Ropartz David , Pérez-Pascual David , Correc Gaëlle , Matard-Mann Maria , Stubbs Keith A. , Rogniaux Hélène , Jeudy Alexandra , Barbeyron Tristan , Médigue Claudine , Czjzek Mirjam , Vallenet David , McBride Mark J. , Duchaud Eric , Michel Gurvan
Published: November 2017

Macroalgae contribute substantially to primary production in coastal ecosystems. Their biomass, mainly consisting of polysaccharides, is cycled into the environment by marine heterotrophic bacteria using largely uncharacterized mechanisms. Here we describe the complete catabolic pathway for carrageenans, major cell wall polysaccharides of red macroalgae, in the marine heterotrophic bacterium Zobellia galactanivorans. Carrageenan catabolism relies on a multifaceted carrageenan-induced regulon, including a non-canonical polysaccharide utilization locus (PUL) and genes distal to the PUL, including a susCD-like pair. The carrageenan utilization system is well conserved in marine Bacteroidetes but modified in other phyla of marine heterotrophic bacteria. The core system is completed by additional functions that might be assumed by non-orthologous genes in different species. This complex genetic structure may be the result of multiple evolutionary events including gene duplications and horizontal gene transfers. These results allow for an extension on the definition of bacterial PUL-mediated polysaccharide digestion.
Gαi is required for carvedilol-induced β1 adrenergic receptor β-arrestin biased signaling
Authors: Wang Jialu , Hanada Kenji , Staus Dean P. , Makara Michael A. , Dahal Giri Raj , Chen Qiang , Ahles Andrea , Engelhardt Stefan , Rockman Howard A.
Published: November 2017

The β1 adrenergic receptor (β1AR) is recognized as a classical Gαs-coupled receptor. Agonist binding not only initiates G protein-mediated signaling but also signaling through the multifunctional adapter protein β-arrestin. Some βAR ligands, such as carvedilol, stimulate βAR signaling preferentially through β-arrestin, a concept known as β-arrestin-biased agonism. Here, we identify a signaling mechanism, unlike that previously known for any Gαs-coupled receptor, whereby carvedilol induces the transition of the β1AR from a classical Gαs-coupled receptor to a Gαi-coupled receptor stabilizing a distinct receptor conformation to initiate β-arrestin-mediated signaling. Recruitment of Gαi is not induced by any other βAR ligand screened, nor is it required for β-arrestin-bias activated by the β2AR subtype of the βAR family. Our findings demonstrate a previously unrecognized role for Gαi in β1AR signaling and suggest that the concept of β-arrestin-bias may need to be refined to incorporate the selective bias of receptors towards distinct G protein subtypes.
Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses
Authors: Zhu Houze , Yan Huanhuan , Tang Na , Li Xinyan , Pang Pei , Li Hao , Chen Wenting , Guo Yu , Shu Shu , Cai You , Pei Lei , Liu Dan , Luo Min-Hua , Man Hengye , Tian Qing , Mu Yangling , Zhu Ling-Qiang , Lu Youming
Published: November 2017

Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival.
Physiological dynamics of stress contagion
Authors: Dimitroff Stephanie J. , Kardan Omid , Necka Elizabeth A. , Decety Jean , Berman Marc G. , Norman Greg J.
Published: November 2017

Can viewing others experiencing stress create a “contagious” physiological stress response in the observer? To investigate second-hand stress, we first created a stimulus set of videos, which featured participants speaking under either minimal stress, high stress, or while recovering from stress. We then recruited a second set of participants to watch these videos. All participants (speakers and observers) were monitored via electrocardiogram. Cardiac activity of the observers while watching the videos was then analyzed and compared to that of the speakers. Furthermore, we assessed dispositional levels of empathy in observers to determine how empathy might be related to the degree of stress contagion. Results revealed that depending on the video being viewed, observers experienced differential changes in cardiac activity that were based on the speaker’s stress level. Additionally, this is the first demonstration that individuals high in dispositional empathy experience these physiological changes more quickly.
MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and jointly sustain NF-κB activity in mercury toxicity
Authors: Ding Enmin , Guo Jun , Bai Ying , Zhang Hengdong , Liu Xin , Cai Wenyan , Zhong Lixin , Zhu Baoli
Published: November 2017

Occupational and environmental exposure to mercury is a public health concern worldwide. Although the altered epigenetic regulatory features, such as microRNA, have been associated with mercury exposure, the underlying molecular mechanism is not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR-486 are novel diagnostic biomarkers of occupational mercury poisoning, and to explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT-qPCR assays and receiver operating characteristics curve analyses were conducted to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of occupational mercury poisoning. Dual-luciferase assay was applied to confirm the target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein expression levels. Cell apoptosis was determined by flow cytometry. Results show that miR-92a and miR-486 expression levels were up-regulated in workers exposed to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial role in mercury toxicity by jointly activating the NF-κB signaling pathway via targeting KLF4 and Cezanne, respectively.
Elevated blood pressure is associated with higher prevalence of low visual acuity among adolescent males in Northeast China
Authors: Zhao Miaomiao , Wang Wei , Yu Han , Ma Yunsheng , Zheng Liqiang , Zhang Lijuan , Wu Guiping , Sun Yingxian , Li Jue
Published: November 2017

The purpose of this study is to track the trends of low visual acuity (VA) from 2005 to 2014, and to investigate its associations with systemic blood pressure (BP) components among adolescents in Northeast China. A total of 55320 students of Han nationality aged 13 to 18 years were included. There has been a significant increase in the prevalence of low VA, with 31.3% in 2005, 40.2% in 2010 and 43.4% in 2014. In multivariable-adjusted logistic regression models, each 1-mm Hg increment in systolic BP (SBP) was associated with 0.8% (95% confidence interval [CI]: 0.1–1.6%), 0.5% (95% CI: 0.1–0.9%) and 1.1% (95% CI: 0.6–1.6%) increased odds of low VA for males in 2005, 2010 and 2014; each 1-mm Hg increment in pulse pressure (PP) was associated with 1.6% (95% CI: 0.7–2.5%), 0.8% (95% CI: 0.4–1.2%) and 1.2% (95% CI: 0.7–1.7%) increased odds of low VA. Higher PP categories had greater odds for low VA compared with the reference group. Similar associations were not observed for females. We conclude that higher prevalence of low VA was significantly associated with higher SBP and PP in males. Furthermore, there was a dose-dependent association between the prevalence of low VA and the levels of PP.
Stochastic fluctuations can reveal the feedback signs of gene regulatory networks at the single-molecule level
Authors: Jia Chen , Xie Peng , Chen Min , Zhang Michael Q.
Published: November 2017

Understanding the relationship between spontaneous stochastic fluctuations and the topology of the underlying gene regulatory network is of fundamental importance for the study of single-cell stochastic gene expression. Here by solving the analytical steady-state distribution of the protein copy number in a general kinetic model of stochastic gene expression with nonlinear feedback regulation, we reveal the relationship between stochastic fluctuations and feedback topology at the single-molecule level, which provides novel insights into how and to what extent a feedback loop can enhance or suppress molecular fluctuations. Based on such relationship, we also develop an effective method to extract the topological information of a gene regulatory network from single-cell gene expression data. The theory is demonstrated by numerical simulations and, more importantly, validated quantitatively by single-cell data analysis of a synthetic gene circuit integrated in human kidney cells.
The role of reproductive isolation in allopolyploid speciation patterns: empirical insights from the progenitors of common wheat
Authors: Matsuoka Yoshihiro , Takumi Shigeo
Published: November 2017

The ability to cause reproductive isolation often varies among individuals within a plant species. We addressed whether such polymorphism influenced speciation of the allopolyploid common wheat (Triticum aestivum L., AABBDD genome) by evaluating the expression of pre-pollination (outcrossing potential) and post-pollination (crossability) barriers in Aegilops tauschii Coss. (the D genome progenitor). In total, 201 Ae. tauschii accessions representing the entire natural habitat range of the species were used for anther length measurement and artificial crosses with a Triticum turgidum L. (the AB genome progenitor) tester. Intraspecific comparisons showed that both barriers were more strongly expressed in the TauL1 lineage than in the TauL2 lineage. The ability of Ae. tauschii to cause reproductive isolation in the hybridisation with T. turgidum might have markedly influenced common wheat’s speciation by inducing lineage-associated patterns of gene flow. The TauL2 accessions with high potential for natural hybridisation with T. turgidum clustered in the southern coastal Caspian region. This provided phenotypic support for the derivation of the D genome of common wheat from southern Caspian populations. The present study underscored the importance of approaches that incorporate the genealogical and geographic structure of the parental species’ reproductive isolation in understanding the mechanism of plant allopolyploid speciation.
Two-Dimensional Co2S2 monolayer with robust ferromagnetism
Authors: Zhang Yun , Pang Jingman , Zhang Meiguang , Gu Xiao , Huang Li
Published: November 2017

Design and synthesis of two-dimensional (2D) materials with robust intrinsic ferromagnetism is highly desirable due to their potential applications in spintronics devices. In this work, we identify a new 2D cobalt sulfide (Co2S2) material by using first-principles calculations and particle swarm optimization (PSO) global structure search. We show that the 2D Co2S2 is most stable in the litharge type tetragonal structure with space group of P4/nmm. The elastic constants, phonon spectrum, and molecular dynamics simulation confirm its mechanical, dynamical and thermal stability, respectively. It is also found that Co2S2 monolayer is a ferromagnetic metal with a Curie temperature up to 404 K. In addition, we propose a feasible procedure to synthesize the Co2S2 monolayer by chemically exfoliating from bulk TlCo2S2 phase.
Liver-specific deletion of RORα aggravates diet-induced nonalcoholic steatohepatitis by inducing mitochondrial dysfunction
Authors: Kim Hyeon-Ji , Han Yong-Hyun , Na Hyelin , Kim Ju-Yeon , Kim Taewook , Kim Hye-Jin , Shin Chanseok , Lee Jung Weon , Lee Mi-Ock
Published: November 2017

Mitochondrial dysfunction may play a key role in the progression of steatosis to nonalcoholic steatohepatitis (NASH); however, the molecular mechanism that controls the structure and function of mitochondria in NASH is not clearly understood. Here, we demonstrated that RORα is a regulator of expression of Bnip3 and PGC-1α, and thereby enhances mitochondrial quality. First, we observed that liver-specific RORα knockout mice (RORα-LKO) were more susceptible to high-fat diet-induced NASH compared with control, probably due to mitochondrial dysfunction. Concordantly, mitochondrial fission in response to nutrient stimuli was abolished with downregulation of Bnip3 and phospho-Drp1 in the hepatocytes of RORα-LKO. RORα enhanced oxygen consumption rate and expression of genes associated with mitochondrial quality control. Finally, we observed the positive correlation of the expression levels of Bnip3 and PGC-1α with those of RORα in patients with steatohepatitis. Together, we demonstrated that RORα mediates mitochondrial quality under nutrient-overloaded conditions and propose RORα as a potential therapeutic target in treatment of NASH.
Picture Interpretation Test (PIT) 360°: An Innovative Measure of Executive Functions
Authors: Serino Silvia , Baglio Francesca , Rossetto Federica , Realdon Olivia , Cipresso Pietro , Parsons Thomas D. , Cappellini Giacomo , Mantovani Fabrizia , De Leo Gianluca , Nemni Raffaello , Riva Giuseppe
Published: November 2017

The assessment of executive functions poses researchers with several challenges related to both the complexity of the construct of executive functions itself and/or the methodological difficulties related to its evaluation. The main objective of the current study was to evaluate a 360° version of an ecologically valid assessment called the Picture Interpretation Test (PIT). Participants included 19 patients with Parkinson’s disease (PD) and 19 healthy controls. All participants endorsed globally positive experiences of the PIT 360°. Furthermore, findings indicated that patients with PD took longer to correctly interpret the PIT 360° scene and tended to significantly focus on details of the 360° scene instead of the most informative elements. The time needed for a correct interpretation of the presented scene also correlated significantly with performance in conventional paper and pencil tests of executive functions for patients with PD. Classification analysis indicated the potential of the PIT 360° for distinguishing between patients with PD and healthy controls. Overall, these data provide preliminary evidence in support of the PIT 360° for evaluating executive functions.
Possible mechanisms of control of Fusarium wilt of cut chrysanthemum by Phanerochaete chrysosporium in continuous cropping fields: A case study
Authors: Li Ping , Chen Jingchao , Li Yi , Zhang Kun , Wang Hailei
Published: November 2017

Continuous cropping is a universal challenge in agriculture because it has adverse physiological effects on plants, resulting in stunting, inferior quality, and even massive loss in harvest due to diseases. In this study, Phanerochaete chrysosporium was inoculated into the field in which cut chrysanthemum had already been continuously cropped for five years to control wilt disease. After 120 days of cultivation, the addition of P. chrysosporium significantly improved the physiological status of plants and changed the bacterial and fungal community structure in the soil. The bacterial quantity in the treatment increased by 1.76 times, but the fungal quantity, especially the quantity of Fusarium oxysporum, decreased significantly in comparison with the control. The investigation into the mechanisms of control of Fusarium wilt of cut chrysanthemum by P. chrysosporium showed that P. chrysosporium in soil can inhibit the growth of F. oxysporum and decrease p-hydroxybenzoic acid (HA), which stimulates the propagation of F. oxysporum. Based on current evidence, the inhibition by P. chrysosporium and change in HA appear to be the main causes of the alleviation of wilt disease in the treatment. Other factors, such as nutrients, might also have an influence on the wilt disease of cut chrysanthemum.