bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns and correlates of major depression in Chinese adults: a cross-sectional study of 0.5 million men and women
Authors: Chen Y. , Bennett D. , Clarke R. , Guo Y. , Yu C. , Bian Z. , Ma L. , Huang Y. , Sun Q. , Zhang N. , Zheng X. , Chen J. , Peto R. , Kendler K. S. , Li L. , Chen Z.
Published: December 2016

Background

Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of adults suffering from major depressive episode (MDE) in China.

Method

A nationwide study recruited 512 891 adults aged 30–79 years from 10 provinces across China during 2004–2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events.

Results

Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE [adjusted OR 14.7, 95% confidence interval (CI) 13.7–15.7], with a dose–response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8–21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4–1.7), low income (OR 2.3, 95% CI 2.1–2.4), living alone (OR 2.6, 95% CI 2.3–3.0), smoking (OR 1.4, 95% CI 1.3–1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide.

Conclusions

Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.
Insights on consciousness from taste memory research
Authors: Gallo Milagros
Published: December 2016

Taste research in rodents supports the relevance of memory in order to determine the content of consciousness by modifying both taste perception and later action. Associated with this issue is the fact that taste and visual modalities share anatomical circuits traditionally related to conscious memory. This challenges the view of taste memory as a type of non-declarative unconscious memory.
Consciousness weaves our internal view of the outside world
Authors: Gur Moshe
Published: December 2016

Low-level consciousness is fundamental to our understanding of the world. Within the conscious field, the constantly changing external visual information is transformed into stable, object-based percepts. Remarkably, holistic objects are perceived while we are cognizant of all of the spatial details comprising the objects and of the relationship between individual elements. This parallel conscious association is unique to the brain. Conscious contributions to motor activity come after our understanding of the world has been established.
Heavy objects and small children: Developmental data extend the passive frame theory
Authors: Hardcastle Cheshire , White Eliah , Kloos Heidi , Hardcastle Valerie Gray
Published: December 2016

Passive frame theory is compatible with modern complexity theory and the idea that conflict drives the emergence of a novel structural organization. After describing new developmental data, we suggest that this conflict needs to be expanded to include not only conflict between action options, but also between action and perception.
Metacognition and conscious experience
Authors: Schwartz Bennett L. , Pournaghdali Ali
Published: December 2016

Morsella et al. focus on the conscious nature of sensation. However, also critical to an understanding of consciousness is the role of internally generated experience, such as the content of autobiographical memory or metacognitive experiences. For example, tip-of-the-tongue states are conscious feelings that arise when recall fails. Internally driven experiences drive us to action and therefore are consistent with the current approach.
IMPLICATION OF ALTERNATIVE MINIMAL CLINICALLY IMPORTANT DIFFERENCE THRESHOLD ESTIMATION METHODS ON TECHNOLOGY ASSESSMENT
Authors: Brixner Diana , Meltzer Eli O. , Morland Kellie , Carroll Cathryn A. , Munzel Ullrich , Lipworth Brian J.
Published: December 2016

Objectives: Various minimal clinically important difference (MCID) threshold estimation techniques have been applied to seasonal allergic rhinitis (SAR). The objectives of this study are to (i) assess the difference in magnitude of alternative SAR MCID threshold estimates and (ii) evaluate the impact of alternative MCID estimates on health technology assessment (HTA).

Methods: Data describing change from baseline of the reflective Total Nasal Symptom Score (rTNSS) for four intranasal SAR treatments were obtained from United States Food and Drug Administration-approved prescribing information. Treatment effects were then compared with anchor-based MCID thresholds derived by Barnes et al. and thresholds obtained from an Agency for Healthcare Research and Quality (AHRQ) panel.

Results: The change in rTNSS score from baseline, represented as the average of the twice-daily recorded scores of the rTNSS, was -2.1 (p < .001) for azelastine hydrochloride 0.10%, 1.35 (p = .014) for ciclesonide, and -1.47 (p < .001) for fluticasone furoate. The change in the rTNSS score from baseline, represented by sum of the AM and PM score, was -2.7 for MP-AzeFlu (p < .001). The rTNSS change from baseline for each product was compared with anchor-based MCID threshold and the AHRQ panel estimates. Comparison of the observed treatment effect to the anchor-based and AHRQ panel MCID thresholds results in different conclusions, with clinically important differences being inferred when anchor-based estimates serve as the reference point.

Conclusion: The AHRQ panel MCID threshold for the rTNSS was twelve times larger than the anchor-based estimates resulting in conflicting recommendations on whether different SAR treatments provide clinically meaningful benefit.
Molecular characterization and genotype shift of dengue virus strains between 2001 and 2014 in Guangzhou
Authors: JIANG L.Y. , JING Q. L. , LIU Y. , CAO Y. M. , SU W. Z. , BIAO D. , YANG Z. C.
Published: December 2016

We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope (E) gene sequences of 67 DENV-1 strains isolated in Guangzhou, together with 58 representative sequences downloaded from NCBI, have shown shifts in viral genotypes. The genotype changed several times, from genotype I to IV in 2002, from IV to I in 2005, and from I to V in 2014. These genotype shifts may be the cause of DENV outbreaks. The diversity of genotypes and clades demonstrates a high risk of future outbreaks in Guangzhou. The mean rate of virus nucleotide substitution in Guangzhou was determined to be 7·77 × 10−4 per site per year, which represents a medium substitution rate compared to two other countries. Our research can point to different ancestors of the isolated strains, which may further reveal the different origins and transmission of DENV-1 strains in Guangzhou.
Alternative results for option pricing and implied volatility in jump-diffusion models using Mellin transforms
Authors: LI T. RAY , RODRIGO MARIANITO R.
Published: December 2016

In this article, we use Mellin transforms to derive alternative results for option pricing and implied volatility estimation when the underlying asset price is governed by jump-diffusion dynamics. The current well known results are restrictive since the jump is assumed to follow a predetermined distribution (e.g., lognormal or double exponential). However, the results we present are general since we do not specify a particular jump-diffusion model within the derivations. In particular, we construct and derive an exact solution to the option pricing problem in a general jump-diffusion framework via Mellin transforms. This approach of Mellin transforms is further extended to derive a Dupire-like partial integro-differential equation, which ultimately yields an implied volatility estimator for assets subjected to instantaneous jumps in the price. Numerical simulations are provided to show the accuracy of the estimator.
“Reverse Permissibility” in the Renewable Energy Sector: Going Beyond the US-India Solar Cells Dispute
Authors: GHORI Umair Hafeez
Published: December 2016

Recent years have witnessed a rise in conflict between WTO members over the use of state subsidies designed to promote the renewable energy sector. Government subsidies are seen by domestic polic-ymakers as a key catalyst in attracting foreign investment, building capacity, and meeting other domestic policy goals. However, subsidies and other state incentivization programmes often carry trade-distorting effects. This paper examines the current state of WTO law and jurisprudence on subsidies extended to achieve environmental goals, in particular the Canada-Renewable Energy/Feed-in Tariff case and the more recent India-Solar Cells case which higlights the localization problem in the renewable energy sector. The case outcome shows that the WTO continues to maintain the status quo by prioritizing free trade over environmental considerations. The paper also discusses the possibility of reform in the GATT/WTO framework for promotion of renewable energy initiatives while maintaining the integrity of the system.
Advances in Intelligence Research: What Should be Expected in the XXI Century (Questions & Answers)
Authors: Colom Roberto
Published: December 2016

Here I briefly delineate my view about the main question of this International Seminar, namely, what should we expecting from the XXI Century regarding the advancements in intelligence research. This view can be summarized as ‘The Brain Connection’ (TBC), meaning that neuroscience will be of paramount relevance for increasing our current knowledge related to the key question: why are some people smarter than others? We need answers to the issue of what happens in our brains when the genotype and the environment are integrated. The scientific community has devoted great research efforts, ranging from observable behavior to hidden genetics, but we are still far from having a clear general picture of what it means to be more or less intelligent. After the discussion held with the panel of experts participating in the seminar, it is concluded that advancements will be more solid and safe increasing the collaboration of scientists with shared research interests worldwide. Paralleling current sophisticated analyses of how the brain computes, nowadays science may embrace a network approach.
East of Japan, Upper Ocean Waves Follow a Seasonal Cycle
Authors: Stanley Sarah
Published: December 2016

The seasonality of fine-scale, near-surface ocean dynamics raises important considerations for an upcoming satellite mission to measure global sea surface height.
Elevated temperature increases carbon and nitrogen fluxes between phytoplankton and heterotrophic bacteria through physical attachment
Authors: Arandia-Gorostidi Nestor , Weber Peter K , Alonso-Sáez Laura , Morán Xosé Anxelu G , Mayali Xavier
Published: December 2016

Quantifying the contribution of marine microorganisms to carbon and nitrogen cycles and their response to predicted ocean warming is one of the main challenges of microbial oceanography. Here we present a single-cell NanoSIMS isotope analysis to quantify C and N uptake by free-living and attached phytoplankton and heterotrophic bacteria, and their response to short-term experimental warming of 4 °C. Elevated temperature increased total C fixation by over 50%, a small but significant fraction of which was transferred to heterotrophs within 12 h. Cell-to-cell attachment doubled the secondary C uptake by heterotrophic bacteria and increased secondary N incorporation by autotrophs by 68%. Warming also increased the abundance of phytoplankton with attached heterotrophs by 80%, and promoted C transfer from phytoplankton to bacteria by 17% and N transfer from bacteria to phytoplankton by 50%. Our results indicate that phytoplankton-bacteria attachment provides an ecological advantage for nutrient incorporation, suggesting a mutualistic relationship that appears to be enhanced by temperature increases.
The effect of extrinsic mortality on genome size evolution in prokaryotes
Authors: Bentkowski Piotr , van Oosterhout Cock , Ashby Ben , Mock Thomas
Published: December 2016

Mortality has a significant role in prokaryotic ecology and evolution, yet the impact of variations in extrinsic mortality on prokaryotic genome evolution has received little attention. We used both mathematical and agent-based models to reveal how variations in extrinsic mortality affect prokaryotic genome evolution. Our results suggest that the genome size of bacteria increases with increased mortality. A high extrinsic mortality increases the pool of free resources and shortens life expectancy, which selects for faster reproduction, a phenotype we called ‘scramblers’. This phenotype is realised by the expansion of gene families involved in nutrient acquisition and metabolism. In contrast, a low mortality rate increases an individual’s life expectancy, which results in natural selection favouring tolerance to starvation when conditions are unfavourable. This leads to the evolution of small, streamlined genomes (‘stayers’). Our models predict that large genomes, gene family expansion and horizontal gene transfer should be observed in prokaryotes occupying ecosystems exposed to high abiotic stress, as well as those under strong predator- and/or pathogen-mediated selection. A comparison of genome size of cyanobacteria in relatively stable marine versus more turbulent freshwater environments corroborates our predictions, although other factors between these environments could also be responsible.
GABAergic anxiolytic drug in water increases migration behaviour in salmon
Authors: Hellström Gustav , Klaminder Jonatan , Finn Fia , Persson Lo , Alanärä Anders , Jonsson Micael , Fick Jerker , Brodin Tomas
Published: December 2016

Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.
Annually resolved North Atlantic marine climate over the last millennium
Authors: Reynolds D. J. , Scourse J. D. , Halloran P. R. , Nederbragt A. J. , Wanamaker A. D. , Butler P. G. , Richardson C. A. , Heinemeier J. , Eiríksson J. , Knudsen K. L. , Hall I. R.
Published: December 2016

Owing to the lack of absolutely dated oceanographic information before the modern instrumental period, there is currently significant debate as to the role played by North Atlantic Ocean dynamics in previous climate transitions (for example, Medieval Climate Anomaly-Little Ice Age, MCA-LIA). Here we present analyses of a millennial-length, annually resolved and absolutely dated marine δ18O archive. We interpret our record of oxygen isotope ratios from the shells of the long-lived marine bivalve Arctica islandica (δ18O-shell), from the North Icelandic shelf, in relation to seawater density variability and demonstrate that solar and volcanic forcing coupled with ocean circulation dynamics are key drivers of climate variability over the last millennium. During the pre-industrial period (AD 1000–1800) variability in the sub-polar North Atlantic leads changes in Northern Hemisphere surface air temperatures at multi-decadal timescales, indicating that North Atlantic Ocean dynamics played an active role in modulating the response of the atmosphere to solar and volcanic forcing.
Structural basis of myelin-associated glycoprotein adhesion and signalling
Authors: Pronker Matti F. , Lemstra Suzanne , Snijder Joost , Heck Albert J. R. , Thies-Weesie Dominique M. E. , Pasterkamp R. Jeroen , Janssen Bert J. C.
Published: December 2016

Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin–axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1. Two post-translational modifications were identified—N-linked glycosylation at the dimerization interface and tryptophan C-mannosylation proximal to the ganglioside binding site—that appear to have regulatory functions. Structure-guided mutations and neurite outgrowth assays demonstrate MAG dimerization and carbohydrate recognition are essential for its regeneration-inhibiting properties. The combination oftransganglioside binding andcishomodimerization explains how MAG maintains the myelin–axon spacing and provides a mechanism for MAG-mediated bi-directional signalling.
Membrane pyrophosphatases from Thermotoga maritima and Vigna radiata suggest a conserved coupling mechanism
Authors: Li Kun-Mou , Wilkinson Craig , Kellosalo Juho , Tsai Jia-Yin , Kajander Tommi , Jeuken Lars J. C. , Sun Yuh-Ju , Goldman Adrian
Published: December 2016

Membrane-bound pyrophosphatases (M-PPases), which couple proton/sodium ion transport to pyrophosphate synthesis/hydrolysis, are important in abiotic stress resistance and in the infectivity of protozoan parasites. Here, three M-PPase structures in different catalytic states show that closure of the substrate-binding pocket by helices 5–6 affects helix 13 in the dimer interface and causes helix 12 to move down. This springs a ‘molecular mousetrap’, repositioning a conserved aspartate and activating the nucleophilic water. Corkscrew motion at helices 6 and 16 rearranges the key ionic gate residues and leads to ion pumping. The pumped ion is above the ion gate in one of the ion-bound structures, but below it in the other. Electrometric measurements show a single-turnover event with a non-hydrolysable inhibitor, supporting our model that ion pumping precedes hydrolysis. We propose a complete catalytic cycle for both proton and sodium-pumping M-PPases, and one that also explains the basis for ion specificity.
Anthropogenic impacts on mosquito populations in North America over the past century
Authors: Rochlin Ilia , Faraji Ary , Ninivaggi Dominick V. , Barker Christopher M. , Kilpatrick A. Marm
Published: December 2016

The recent emergence and spread of vector-borne viruses including Zika, chikungunya and dengue has raised concerns that climate change may cause mosquito vectors of these diseases to expand into more temperate regions. However, the long-term impact of other anthropogenic factors on mosquito abundance and distributions is less studied. Here, we show that anthropogenic chemical use (DDT; dichlorodiphenyltrichloroethane) and increasing urbanization were the strongest drivers of changes in mosquito populations over the last eight decades in areas on both coasts of North America. Mosquito populations have increased as much as tenfold, and mosquito communities have become two- to fourfold richer over the last five decades. These increases are correlated with the decay in residual environmental DDT concentrations and growing human populations, but not with temperature. These results illustrate the far-reaching impacts of multiple anthropogenic disturbances on animal communities and suggest that interactions between land use and chemical use may have unforeseen consequences on ecosystems.
PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation
Authors: Nagai Yuji , Kikuchi Erika , Lerchner Walter , Inoue Ken-ichi , Ji Bin , Eldridge Mark A. G. , Kaneko Hiroyuki , Kimura Yasuyuki , Oh-Nishi Arata , Hori Yukiko , Kato Yoko , Hirabayashi Toshiyuki , Fujimoto Atsushi , Kumata Katsushi , Zhang Ming-Rong , Aoki Ichio , Suhara Tetsuya , Higuchi Makoto , Takada Masahiko , Richmond Barry J. , Minamimoto Takafumi
Published: December 2016

The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET). PET imaging provides information critical for successful chemogenetic silencing during experiments, in this case the location and level of hM4Di expression, and the relationship between agonist dose and hM4Di receptor occupancy. Here we demonstrate that inactivating bilateral rmCD through activation of hM4Di produces a significant and reproducible loss of sensitivity to reward value in monkeys. Thus, the rmCD is involved in making normal judgments about the value of reward.
Large differences in regional precipitation change between a first and second 2 K of global warming
Authors: Good Peter , Booth Ben B. B. , Chadwick Robin , Hawkins Ed , Jonko Alexandra , Lowe Jason A.
Published: December 2016

For adaptation and mitigation planning, stakeholders need reliable information about regional precipitation changes under different emissions scenarios and for different time periods. A significant amount of current planning effort assumes that each K of global warming produces roughly the same regional climate change. Here using 25 climate models, we compare precipitation responses with three 2 K intervals of global ensemble mean warming: a fast and a slower route to a first 2 K above pre-industrial levels, and the end-of-century difference between high-emission and mitigation scenarios. We show that, although the two routes to a first 2 K give very similar precipitation changes, a second 2 K produces quite a different response. In particular, the balance of physical mechanisms responsible for climate model uncertainty is different for a first and a second 2 K of warming. The results are consistent with a significant influence from nonlinear physical mechanisms, but aerosol and land-use effects may be important regionally.
Erratum: Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides
Authors: Cheung Chi Wai , Hu Xile
Published: December 2016

Nature Communications 7: Article number: 12494 (2016); Published 12 August 2016; Updated 6 December 2016 In Fig. 7a of this article, the structure of the intermediate compound was inadvertently misdrawn during the production process. The correct version of Fig. 7 appears below as Fig. 1.
Erratum: Phylogenetic and functional potential links pH and N2O emissions in pasture soils
Authors: Samad Md Sainur , Biswas Ambarish , Bakken Lars R. , Clough Timothy J. , de Klein Cecile A. M. , Richards Karl G. , Lanigan Gary J. , Morales Sergio E.
Published: December 2016

Scientific Reports 6: Article number: 35990; published online: 26 October 2016; updated: 06 December 2016.
Passivation and characterization of charge defects in ambipolar silicon quantum dots
Authors: Spruijtenburg Paul C. , Amitonov Sergey V. , Mueller Filipp , van der Wiel Wilfred G. , Zwanenburg Floris A.
Published: December 2016

In this Report we show the role of charge defects in the context of the formation of electrostatically defined quantum dots. We introduce a barrier array structure to probe defects at multiple locations in a single device. We measure samples both before and after an annealing process which uses an Al2O3 overlayer, grown by atomic layer deposition. After passivation of the majority of charge defects with annealing we can electrostatically define hole quantum dots up to 180 nm in length. Our ambipolar structures reveal amphoteric charge defects that remain after annealing with charging energies of "Equation missing"10 meV in both the positive and negative charge state.
Chemically induced oxidative stress affects ASH neuronal function and behavior in C. elegans
Authors: Gourgou Eleni , Chronis Nikos
Published: December 2016

Oxidative stress (OS) impact on a single neuron’s function in vivo remains obscure. Using C. elegans as a model organism, we report the effect of paraquat (PQ)-induced OS on wild type worms on the function of the ASH polymodal neuron. By calcium (Ca2+) imaging, we quantified ASH activation upon stimulus delivery. PQ-treated worms displayed higher maximum depolarization (peak of the Ca2+ transients) compared to untreated animals. PQ had a similar effect on the ASH neuron response time (rising slope of the Ca2+ transients), except in very young worms. OS effect on ASH was partially abolished in vitamin C-treated worms. We performed octanol and osmotic avoidance tests, to investigate the OS effect on ASH-dependent behaviors. PQ-treated worms have enhanced avoidance behavior compared to untreated ones, suggesting that elevated ASH Ca2+ transients result in enhanced ASH-mediated behavior. The above findings suggest a possible hormetic effect of PQ, as a factor inducing mild oxidative stress. We also quantified locomotion parameters (velocity, bending amplitude), which are not mediated by ASH activation. Bending amplitude did not differ significantly between treated and untreated worms; velocity in older adults decreased. The differential effect of OS on behavioral patterns may mirror a selective impact on the organism’s neurons.
Human mesenchymal stromal cells exert HGF dependent cytoprotective effects in a human relevant pre-clinical model of COPD
Authors: Kennelly Helen , Mahon Bernard P. , English Karen
Published: December 2016

Bone-marrow derived mesenchymal stromal cells (MSCs) have potent immunomodulatory and tissue reparative properties, which may be beneficial in the treatment of inflammatory diseases such as COPD. This study examined the mechanisms by which human MSCs protect against elastase induced emphysema. Using a novel human relevant pre-clinical model of emphysema the efficacy of human MSC therapy and optimal cell dose were investigated. Protective effects were examined in the lung through histological examination. Further in vivo experiments examined the reparative abilities of MSCs after tissue damage was established and the role played by soluble factors secreted by MSCs. The mechanism of MSC action was determined in using shRNA gene knockdown. Human MSC therapy and MSC conditioned media exerted significant cytoprotective effects when administered early at the onset of the disease. These protective effects were due to significant anti-inflammatory, anti-fibrotic and anti-apoptotic mechanisms, mediated in part through MSC production of hepatocyte growth factor (HGF). When MSC administration was delayed, significant protection of the lung architecture was observed but this was less extensive. MSC cell therapy was more effective than MSC conditioned medium in this emphysema model.
Electrophysiological Properties of CA1 Pyramidal Neurons along the Longitudinal Axis of the Mouse Hippocampus
Authors: Milior Giampaolo , Di Castro Maria Amalia , Sciarria Livio Pepe’ , Garofalo Stefano , Branchi Igor , Ragozzino Davide , Limatola Cristina , Maggi Laura
Published: December 2016

Evidence for different physiological properties along the hippocampal longitudinal axis is emerging. Here, we examined the electrophysiological features of neurons at different dorso-ventral sites of the mouse CA1 hippocampal region. Cell position was defined with respect to longitudinal coordinates of each slice. We measured variations in neuronal excitability, subthreshold membrane properties and neurotransmitter responses along the longitudinal axis. We found that (i) pyramidal cells of the dorsal hippocampus (DH) were less excitable than those of the ventral hippocampus (VH). Resting Membrane Potential (RMP) was more hyperpolarized and somatic Input Resistance (Ri) was lower in DH compared to VH. (ii) The Paired-pulse ratio (PPR) of focally induced synaptic responses was systematically reduced from the DH to the VH; (iii) Long-term-potentiation was most pronounced in the DH and fell gradually in the intermediate hippocampus and in the VH; (iv) the frequency of miniature GABAergic events was higher in the VH than in the DH; (v) the PPR of evoked inhibitory post-synaptic current (IPSC) was higher in the DH than in the VH. These findings indicate an increased probability of both GABA and glutamate release and a reduced plasticity in the ventral compared to more dorsal regions of the hippocampus.
Design and mechanistic insight into ultrafast calcium indicators for monitoring intracellular calcium dynamics
Authors: Helassa Nordine , Podor Borbala , Fine Alan , Török Katalin
Published: December 2016

Calmodulin-based genetically encoded fluorescent calcium indicators (GCaMP-s) are powerful tools of imaging calcium dynamics from cells to freely moving animals. High affinity indicators with slow kinetics however distort the temporal profile of calcium transients. Here we report the development of reduced affinity ultrafast variants of GCaMP6s and GCaMP6f. We hypothesized that GCaMP-s have a common kinetic mechanism with a rate-limiting process in the interaction of the RS20 peptide and calcium-calmodulin. Therefore we targeted specific residues in the binding interface by rational design generating improved indicators with GCaMP6fu displaying fluorescence rise and decay times (t1/2) of 1 and 3 ms (37 °C) in vitro, 9 and 22-fold faster than GCaMP6f respectively. In HEK293T cells, GCaMP6fu revealed a 4-fold faster decay of ATP-evoked intracellular calcium transients than GCaMP6f. Stimulation of hippocampal CA1 pyramidal neurons with five action potentials fired at 100 Hz resulted in a single dendritic calcium transient with a 2-fold faster rise and 7-fold faster decay time (t1/2 of 40 ms) than GCaMP6f, indicating that tracking high frequency action potentials may be limited by calcium dynamics. We propose that the design strategy used for generating GCaMP6fu is applicable for the acceleration of the response kinetics of GCaMP-type calcium indicators.
Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle
Authors: Laurens Claire , Bourlier Virginie , Mairal Aline , Louche Katie , Badin Pierre-Marie , Mouisel Etienne , Montagner Alexandra , Marette André , Tremblay Angelo , Weisnagel John S. , Guillou Hervé , Langin Dominique , Joanisse Denis R. , Moro Cedric
Published: December 2016

Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges. We show that PLIN5 protein is elevated in endurance-trained (ET) subjects and correlates with muscle oxidative capacity and whole-body insulin sensitivity. When overexpressed in human skeletal muscle cells to recapitulate the ET phenotype, PLIN5 diminishes lipolysis and FA oxidation under basal condition, but paradoxically enhances FA oxidation during forskolin- and contraction- mediated lipolysis. Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we demonstrate that down-regulation of PLIN5 in skeletal muscle inhibits insulin-mediated glucose uptake under normal chow feeding condition, while paradoxically improving insulin sensitivity upon high-fat feeding. These data highlight a key role of PLIN5 in LD function, first by finely adjusting LD FA supply to mitochondrial oxidation, and second acting as a protective factor against lipotoxicity in skeletal muscle.
Ancient tortoise hunting in the southwest Pacific
Authors: Hawkins Stuart , Worthy Trevor H. , Bedford Stuart , Spriggs Matthew , Clark Geoffrey , Irwin Geoff , Best Simon , Kirch Patrick
Published: December 2016

We report the unprecedented Lapita exploitation and subsequent extinction of large megafauna tortoises (?Meiolania damelipi) on tropical islands during the late Holocene over a 281,000 km2 region of the southwest Pacific spanning from the Vanuatu archipelago to Viti Levu in Fiji. Zooarchaeological analyses have identified seven early archaeological sites with the remains of this distinctive hornless tortoise, unlike the Gondwanan horned meiolaniid radiation to the southwest. These large tortoise radiations in the Pacific may have contributed to the rapid dispersal of early mobile Neolithic hunters throughout southwest Melanesia and on to western Polynesia. Subsequent rapid extinctions of these terrestrial herbivorous megafauna are likely to have led to significant changes in ecosystems that help explain changes in current archaeological patterns from Post-Lapita contexts in the region.
Molecular Structure and Dynamics of Water on Pristine and Strained Phosphorene: Wetting and Diffusion at Nanoscale
Authors: Zhang Wei , Ye Chao , Hong Linbi , Yang Zaixing , Zhou Ruhong
Published: December 2016

Phosphorene, a newly fabricated two-dimensional (2D) nanomaterial, has emerged as a promising material for biomedical applications with great potential. Nonetheless, understanding the wetting and diffusive properties of bio-fluids on phosphorene which are of fundamental importance to these applications remains elusive. In this work, using molecular dynamics (MD) simulations, we investigated the structural and dynamic properties of water on both pristine and strained phosphorene. Our simulations indicate that the diffusion of water molecules on the phosphorene surface is anisotropic, with strain-enhanced diffusion clearly present, which arises from strain-induced smoothing of the energy landscape. The contact angle of water droplet on phosphorene exhibits a non-monotonic variation with the transverse strain. The structure of water on transverse stretched phosphorene is demonstrated to be different from that on longitudinal stretched phosphorene. Moreover, the contact angle of water on strained phosphorene is proportional to the quotient of the longitudinal and transverse diffusion coefficients of the interfacial water. These findings thereby offer helpful insights into the mechanism of the wetting and transport of water at nanoscale, and provide a better foundation for future biomedical applications of phosphorene.
Convex Analysis of Mixtures for Separating Non-negative Well-grounded Sources
Authors: Zhu Yitan , Wang Niya , Miller David J. , Wang Yue
Published: December 2016

Blind Source Separation (BSS) is a powerful tool for analyzing composite data patterns in many areas, such as computational biology. We introduce a novel BSS method, Convex Analysis of Mixtures (CAM), for separating non-negative well-grounded sources, which learns the mixing matrix by identifying the lateral edges of the convex data scatter plot. We propose and prove a sufficient and necessary condition for identifying the mixing matrix through edge detection in the noise-free case, which enables CAM to identify the mixing matrix not only in the exact-determined and over-determined scenarios, but also in the under-determined scenario. We show the optimality of the edge detection strategy, even for cases where source well-groundedness is not strictly satisfied. The CAM algorithm integrates plug-in noise filtering using sector-based clustering, an efficient geometric convex analysis scheme, and stability-based model order selection. The superior performance of CAM against a panel of benchmark BSS techniques is demonstrated on numerically mixed gene expression data of ovarian cancer subtypes. We apply CAM to dissect dynamic contrast-enhanced magnetic resonance imaging data taken from breast tumors and time-course microarray gene expression data derived from in-vivo muscle regeneration in mice, both producing biologically plausible decomposition results.
Risk assessment of recent Egyptian H5N1 influenza viruses
Authors: Arafa A.-S. , Yamada S. , Imai M. , Watanabe T. , Yamayoshi S. , Iwatsuki-Horimoto K. , Kiso M. , Sakai-Tagawa Y. , Ito M. , Imamura T. , Nakajima N. , Takahashi K. , Zhao D. , Oishi K. , Yasuhara A. , Macken C. A. , Zhong G. , Hanson A. P. , Fan S. , Ping J. , Hatta M. , Lopes T. J. S. , Suzuki Y. , El-Husseiny M. , Selim A. , Hagag N. , Soliman M. , Neumann G. , Hasegawa H. , Kawaoka Y.
Published: December 2016

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are enzootic in poultry populations in different parts of the world, and have caused numerous human infections in recent years, particularly in Egypt. However, no sustained human-to-human transmission of these viruses has yet been reported. We tested nine naturally occurring Egyptian H5N1 viruses (isolated in 2014–2015) in ferrets and found that three of them transmitted via respiratory droplets, causing a fatal infection in one of the exposed animals. All isolates were sensitive to neuraminidase inhibitors. However, these viruses were not transmitted via respiratory droplets in three additional transmission experiments in ferrets. Currently, we do not know if the efficiency of transmission is very low or if subtle differences in experimental parameters contributed to these inconsistent results. Nonetheless, our findings heighten concern regarding the pandemic potential of recent Egyptian H5N1 influenza viruses.
Photoelectrochemical detection of alpha-fetoprotein based on ZnO inverse opals structure electrodes modified by Ag2S nanoparticles
Authors: Jiang Yandong , Liu Dali , Yang Yudan , Xu Ru , Zhang Tianxiang , Sheng Kuang , Song Hongwei
Published: December 2016

In this work, a new photoelectrochemical biosensor based on Ag2S nanoparticles (NPs) modified macroporous ZnO inverse opals structure (IOs) was developed for sensitive and rapid detection of alpha fetal protein (AFP). Small size and uniformly dispersed Ag2S NPs were prepared using the Successive Ionic Layer Adsorption And Reaction (SILAR) method, which were adsorbed on ZnO IOs surface and frame work as matrix for immobilization of AFP. The composite structure of ZnO/Ag2S expanded the scope of light absorption to long wavelength, which can make full use of the light energy. Meanwhile, an effective matching of energy levels between the conduction bands of Ag2S and ZnO are beneficial to the photo-generated electrons transfer. The biosensors based on FTO (fluorine-doped tinoxide) ZnO/Ag2S electrode showed enough sensitivity and a wide linear range from 0.05 ng/mL to 200 ng/mL with a low detection limit of 8 pg/mL for the detection of AFP. It also exhibited high reproducibility, specificity and stability. The proposed method was potentially attractive for achieving excellent photoelectrochemical biosensor for detection of other proteins.
Enantiomer signature and carbon isotope evidence for the migration and transformation of DDTs in arable soils across China
Authors: Niu Lili , Xu Chao , Zhu Siyu , Bao Huiming , Xu Yang , Li Hongyi , Zhang Zhijian , Zhang Xichang , Qiu Jiguo , Liu Weiping
Published: December 2016

Due to the adverse impact of DDTs on ecosystems and humans, a full fate assessment deems a comprehensive study on their occurrence in soils over a large region. Through a sampling campaign across China, we measured the concentrations, enantiomeric fractions (EFs), compound-specific carbon isotope composition of DDT and its metabolites, and the microbial community in related arable soils. The geographically total DDT concentrations are higher in eastern than western China. The EFs and δ13C of o,p’-DDT in soils from western China show smaller deviations from those of racemic/standard compound, indicating the DDT residues there mainly result from atmospheric transport. However, the sources of DDT in eastern China are mainly from historic application of technical DDTs and dicofol. The inverse dependence of o,p’-DDT and p,p’-DDE on temperature evidences the transformation of parent DDT to its metabolites. Initial usage, abiotic parameters and microbial communities are found to be the main factors influencing the migration and transformation of DDT isomers and their metabolites in soils. In addition, a prediction equation of DDT concentrations in soils based on stepwise multiple regression analysis is developed. Results from this study offer insights into the migration and transformation pathways of DDTs in Chinese arable soils, which will allow data-based risk assessment on their use.
Interplay of coupling and common noise at the transition to synchrony in oscillator populations
Authors: Pimenova Anastasiya V. , Goldobin Denis S. , Rosenblum Michael , Pikovsky Arkady
Published: December 2016

There are two ways to synchronize oscillators: by coupling and by common forcing, which can be pure noise. By virtue of the Ott-Antonsen ansatz for sine-coupled phase oscillators, we obtain analytically tractable equations for the case where both coupling and common noise are present. While noise always tends to synchronize the phase oscillators, the repulsive coupling can act against synchrony, and we focus on this nontrivial situation. For identical oscillators, the fully synchronous state remains stable for small repulsive coupling; moreover it is an absorbing state which always wins over the asynchronous regime. For oscillators with a distribution of natural frequencies, we report on a counter-intuitive effect of dispersion (instead of usual convergence) of the oscillators frequencies at synchrony; the latter effect disappears if noise vanishes.
Correction: Corrigendum: Astrocytic Acid-Sensing Ion Channel 1a Contributes to the Development of Chronic Epileptogenesis
Authors: Yang Feng , Sun Xiaolong , Ding Yinxiu , Ma Hui , Yang Tangpeng Ou , Ma Yue , Wei Dong , Li Wen , Xu Tianle , Jiang Wen
Published: December 2016

Scientific Reports 6: Article number: 31581; published online: 16 August 2016; updated: 06 December 2016
In-situ one-step synthesis of carbon-encapsulated naked magnetic metal nanoparticles conducted without additional reductants and agents
Authors: Kang Jun , Kim Yeonwon , Kim Hye-min , Hu Xiulan , Saito Nagahiro , Choi Jae-Hyuk , Lee Myeong-Hoon
Published: December 2016

C-encapsulated highly pure Ni, Co, and Fe magnetic nanoparticles (MNPs/C) were synthesized by an innovative one-step in-situ plasma in liquid method (solution plasma processing, SPP) without any additional reductants, agents, or treatment. Successful encapsulation of MNPs was demonstrated by using inductively coupled plasma-atomic emission spectrometry and cyclic voltammetry techniques. The obtained X-ray diffraction patterns and transmission electron microscopy images corresponded to MNPs with average diameters of 5 nm and good crystalline structure. The C capsules with spherical shapes (containing onion-like layers) were characterized by uniform sizes (ranging from 20 nm to 30 nm) and chain-like morphologies. The synthesized MNPs/C exhibited superparamagnetic properties at room temperature and might be utilized in data storage, biomedical, and energy applications since various NPs (including bimetallic ones) could be easily prepared by changing working electrodes. This study shows the potential of SPP to be a candidate for the next-generation synthesis method of NPs/C.
Comparison of 432 Pseudomonas strains through integration of genomic, functional, metabolic and expression data
Authors: Koehorst Jasper J. , van Dam Jesse C. J. , van Heck Ruben G. A. , Saccenti Edoardo , dos Santos Vitor A. P. Martins , Suarez-Diez Maria , Schaap Peter J.
Published: December 2016

Pseudomonas is a highly versatile genus containing species that can be harmful to humans and plants while others are widely used for bioengineering and bioremediation. We analysed 432 sequenced Pseudomonas strains by integrating results from a large scale functional comparison using protein domains with data from six metabolic models, nearly a thousand transcriptome measurements and four large scale transposon mutagenesis experiments. Through heterogeneous data integration we linked gene essentiality, persistence and expression variability. The pan-genome of Pseudomonas is closed indicating a limited role of horizontal gene transfer in the evolutionary history of this genus. A large fraction of essential genes are highly persistent, still non essential genes represent a considerable fraction of the core-genome. Our results emphasize the power of integrating large scale comparative functional genomics with heterogeneous data for exploring bacterial diversity and versatility.
IP3 accumulation and/or inositol depletion: two downstream lithium’s effects that may mediate its behavioral and cellular changes
Authors: Sade Y , Toker L , Kara N Z , Einat H , Rapoport S , Moechars D , Berry G T , Bersudsky Y , Agam G
Published: December 2016

Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate—the consequences of lithium’s inhibition of inositol monophosphatase at therapeutically relevant concentrations (the ‘inositol depletion’ hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol depletion per se, or phosphoinositols accumulation induces the beneficial effects, we utilized knockout mice of either of two inositol metabolism-related genes—IMPA1 or SMIT1, both mimic several lithium’s behavioral and biochemical effects. We assessed in vivo, under non-agonist-stimulated conditions, 3H-inositol incorporation into brain phosphoinositols and phosphoinositides in wild-type, lithium-treated, IMPA1 and SMIT1 knockout mice. Lithium treatment increased frontal cortex and hippocampal phosphoinositols labeling by several fold, but decreased phosphoinositides labeling in the frontal cortex of the wild-type mice of the IMPA1 colony strain by ~50%. Inositol metabolites were differently affected by IMPA1 and SMIT1 knockout. Inositoltrisphosphate administered intracerebroventricularly affected bipolar-related behaviors and autophagy markers in a lithium-like manner. Namely, IP3 but not IP1 reduced the immobility time of wild-type mice in the forced swim test model of antidepressant action by 30%, an effect that was reversed by an antagonist of all three IP3 receptors; amphetamine-induced hyperlocomotion of wild-type mice (distance traveled) was 35% reduced by IP3 administration; IP3 administration increased hippocampal messenger RNA levels of Beclin-1 (required for autophagy execution) and hippocampal and frontal cortex protein levels ratio of Beclin-1/p62 by about threefold (p62 is degraded by autophagy). To conclude, lithium affects the phosphatidylinositol signaling system in two ways: depleting inositol, consequently decreasing phosphoinositides; elevating inositol monophosphate levels followed by phosphoinositols accumulation. Each or both may mediate lithium-induced behavior.