bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrethroid and carbamate resistance in Australian Helicoverpa armigera (Lepidoptera: Noctuidae) from 2008 to 2015: what has changed since the introduction of Bt cotton?
Authors: Bird L.J.
Published: January 2018

Pyrethroid and carbamate resistance was evaluated in Helicoverpa armigera from 2008 to 2015. Insects were collected as eggs primarily from cultivated hosts in the major cropping areas of New South Wales and Queensland, Australia. Larvae reared from eggs were tested for resistance to fenvalerate, bifenthrin or methomyl in the F0 generation using a topical application of a discriminating dose of insecticide. In 2008–2009, resistance to fenvalerate was 71% and no resistance to bifenthrin was recorded. In the following two seasons, resistance to pyrethroids was relatively stable with fenvalerate resistance ranging from 63% to 67% and bifenthrin resistance ranging from 5.6% and 6.4% in 2009–2010 and 2010–2011, respectively. However, in 2011–2012, pyrethroid resistance had increased to 91% and 36% for fenvalerate and bifenthrin, respectively. Resistance remained above 90% for fenvalerate and above 35% for bifenthrin in the following three seasons from 2012 to 2015. In 2008–2009, methomyl resistance was 33% and declined to 22% and 15% in 2009–2010 and 2010–2011, respectively. Methomyl resistance remained at moderate levels from 2011–12 to 2014–15, ranging from 21% to 40%. Factors that influenced selection pressure of pyrethroid and carbamate insecticides and impacted resistance frequency in H. armigera may have been associated with changes in the composition of the cropping landscape. The rapid expansion of the pulse industry and the commensurate increased use of insecticide may have played a role in reselection of high-level pyrethroid resistance, and highlights the need for an urgent and strategic response to insecticide resistance management in the Australian grains industry.
Sensing the ground: On the global politics of satellite-based activism
Authors: Rothe Delf , Shim David
Published: January 2018

In recent years, satellite imagery, previously restricted to the defence and intelligence communities, has been made available to a range of non-state actors as well. Non-governmental organisations, journalists, and celebrities such as George Clooney now use remote sensing data like digital Sherlock Holmeses to investigate and reveal human rights abuses, political violence, environmental destruction, and eco-crimes from a distance. It is often said that the increasing availability and applicability of remote sensing technologies has contributed to the rise of what can be called ‘satellite-based activism’ empowering non-state groups to challenge state practices of seeing and showing. In this article we argue that NGO activism is not challenging the sovereign gaze of the state but, on the contrary, actually reinforcing it. We will bolster our arguments in this regard in two prominent fields of non-governmental remote sensing: human rights and environmental governance.
Multiemployer plans: evaluating a proposal to spread the pain
Authors: MUNNELL ALICIA , AUBRY JEAN-PIERRE , HOU WENLIANG , WEBB ANTHONY
Published: January 2018

The Multiemployer Pension Reform Act (MPRA) allows multiemployer plans facing insolvency to apply for approval from the Treasury to cut accrued benefits of plan members to prolong plan solvency—a departure from the benefit protections of Employee Retirement Income Security Act. To assess the law's impact, this paper models Central States Teamsters – by far the largest – plan to have applied under the new law to reduce benefits. Using a stochastic model of future investment returns, the probability of insolvency within 10 years drops from 50% (without cuts) to 6% (with cuts). While benefit cuts increase the overall welfare of participants by extending the plan's life, the welfare of younger retirees (under age 75) worsens and welfare of workers improves.
Beyond fresh and direct: exploring the specialty food industry as a market outlet for small- and medium-sized farms
Authors: Feenstra Gail , Hardesty Shermain , Lev Larry , Houston Laurie , King Robert , Joannides Jan
Published: January 2018

As small- and medium-sized farms struggle to remain viable in a competitive global economy, the expanding specialty food industry provides a potential marketing opportunity. These farms raise many of the farm products that can become the key ingredients in value-added foods. Little research exists about processed specialty foods made from locally/regionally sourced ingredients produced by small- and medium-sized farms. This study investigates the benefits, barriers and challenges for small- and medium-sized farmers who want to sell products to specialty food manufacturers (SFMs). This paper analyzes 240 survey responses from dairy, meat, fruit/vegetable/nuts and grain specialty manufacturers and 60 in-depth interviews of these manufacturers and farmers in California, Minnesota, Wisconsin, Washington and Oregon. We found that almost half of the manufacturers surveyed source primary ingredients directly from farms or from their own farm. More than half of the farms that supply these key ingredients are small or medium-sized, indicating that many farms in this category are already successfully supplying SFMs with key ingredients. The key benefits manufacturers receive from working with these farms included quality assurance, trust, and traceability. Key obstacles to such farmer/manufacturer transactions are: cost, inability to meet volume requirements, unreliable supply and lack of year-round supply. The nature of relationships between manufacturers and farmers emerged as a theme that influences the success of small- and medium-sized farms as ingredient suppliers. Whether they were large or small, most manufacturers purchased their key ingredients from multiple suppliers in order to reduce their risk. Overall, we find evidence that the specialty food industry is an emerging market channel for small- and medium-sized farms. We also find that to be successful suppliers of SFMs, farmers need to have processes in place to ensure the quality of their products; provide the specific attributes the manufacturer requires for its ingredients and be willing to communicate frequently with the manufacturer.
Energy limitation of cyanophage development: implications for marine carbon cycling
Authors: Puxty Richard J , Evans David J , Millard Andrew D , Scanlan David J
Published: January 2018

Marine cyanobacteria are responsible for ~25% of the fixed carbon that enters the ocean biosphere. It is thought that abundant co-occurring viruses play an important role in regulating population dynamics of cyanobacteria and thus the cycling of carbon in the oceans. Despite this, little is known about how viral infections ‘play-out’ in the environment, particularly whether infections are resource or energy limited. Photoautotrophic organisms represent an ideal model to test this since available energy is modulated by the incoming light intensity through photophosphorylation. Therefore, we exploited phototrophy of the environmentally relevant marine cyanobacterium Synechococcus and monitored growth of a cyanobacterial virus (cyanophage). We found that light intensity has a marked effect on cyanophage infection dynamics, but that this is not manifest by a change in DNA synthesis. Instead, cyanophage development appears energy limited for the synthesis of proteins required during late infection. We posit that acquisition of auxiliary metabolic genes (AMGs) involved in light-dependent photosynthetic reactions acts to overcome this limitation. We show that cyanophages actively modulate expression of these AMGs in response to light intensity and provide evidence that such regulation may be facilitated by a novel mechanism involving light-dependent splicing of a group I intron in a photosynthetic AMG. Altogether, our data offers a mechanistic link between diurnal changes in irradiance and observed community level responses in metabolism, i.e., through an irradiance-dependent, viral-induced release of dissolved organic matter (DOM).
Climate change promotes parasitism in a coral symbiosis
Authors: Baker David M , Freeman Christopher J , Wong Jane C Y , Fogel Marilyn L , Knowlton Nancy
Published: January 2018

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals’ sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change.
The real-life costs of emotion regulation in anorexia nervosa: a combined ecological momentary assessment and fMRI study
Authors: Seidel Maria , King Joseph A. , Ritschel Franziska , Boehm Ilka , Geisler Daniel , Bernardoni Fabio , Holzapfel Larissa , Diestel Stefan , Diers Kersten , Strobel Alexander , Goschke Thomas , Walter Henrik , Roessner Veit , Ehrlich Stefan
Published: January 2018

Regulation of emotions is necessary for successful attainment of short-term and long-term goals. However, over-regulation may also have its costs. In anorexia nervosa (AN), forgoing food intake despite emaciation and endocrine signals that promote eating is an example of “too much” self-control. Here we investigated whether voluntary emotion regulation in AN patients comes with associated disorder-relevant costs. Thirty-five patients with acute AN and thirty-five age-matched healthy controls (HCs) performed an established emotion regulation paradigm during functional magnetic resonance imaging after an overnight fast. The task required reducing emotions induced by positively valenced pictures via distancing. We calculated a neural regulation score from responses recorded in a reward-related brain region of interest (ventral striatum; VS) by subtracting activation measured on “positive distance” trials from that elicited under the “positive watch” (baseline) condition. Complementing the imaging data, we used ecological momentary assessment (EMA) to probe disorder-related rumination and affect six times/day for 2 weeks following the scanning session. The neural regulation score indicating reduced VS activation during emotion regulation was used as a predictor in hierarchical linear models with EMA measures as outcomes. No group differences in neural activity were found for the main contrasts of the task. However, regulation of VS activity was associated with increased body-related rumination and increased negative affect in AN, but not in HC. In line with this finding, correlational analysis with longitudinal BMI measurements revealed a link between greater VS regulation and poorer treatment outcome after 60 and 90 days. Together, these results identify a neural correlate of altered emotion regulation in AN, which seems to be detrimental to psychological well-being and may interfere with recovery.
Experimental quantum verification in the presence of temporally correlated noise
Authors: Mavadia S. , Edmunds C. L. , Hempel C. , Ball H. , Roy F. , Stace T. M. , Biercuk M. J.
Published: January 2018

Growth in the capabilities of quantum information hardware mandates access to techniques for performance verification that function under realistic laboratory conditions. Here we experimentally characterise the impact of common temporally correlated noise processes on both randomised benchmarking (RB) and gate-set tomography (GST). Our analysis highlights the role of sequence structure in enhancing or suppressing the sensitivity of quantum verification protocols to either slowly or rapidly varying noise, which we treat in the limiting cases of quasi-DC miscalibration and white noise power spectra. We perform experiments with a single trapped 171Yb+ ion-qubit and inject engineered noise $$\left( { \propto \hat \sigma _z} \right)$$

∝

σ

^

z

to probe protocol performance. Experiments on RB validate predictions that measured fidelities over sequences are described by a gamma distribution varying between approximately Gaussian, and a broad, highly skewed distribution for rapidly and slowly varying noise, respectively. Similarly we find a strong gate set dependence of default experimental GST procedures in the presence of correlated errors, leading to significant deviations between estimated and calculated diamond distances in the presence of correlated $$\hat \sigma _z$$

σ

^

z

errors. Numerical simulations demonstrate that expansion of the gate set to include negative rotations can suppress these discrepancies and increase reported diamond distances by orders of magnitude for the same error processes. Similar effects do not occur for correlated $$\hat \sigma _x$$

σ

^

x

or $$\hat \sigma _y$$

σ

^

y

errors or depolarising noise processes, highlighting the impact of the critical interplay of selected gate set and the gauge optimisation process on the meaning of the reported diamond norm in correlated noise environments.
Optical breakdown of solids by few-cycle laser pulses
Authors: Zhokhov P. A. , Zheltikov A. M.
Published: January 2018

We show that a broadly accepted criterion of laser-induced breakdown in solids, defining the laser-breakdown threshold in terms of the laser fluence or laser intensity needed to generate a certain fraction of the critical electron density rc within the laser pulse, fails in the case of high-intensity few-cycle laser pulses. Such laser pulses can give rise to subcycle oscillations of electron density ρ with peak ρ values well above ρc even when the total energy of the laser pulse is too low to induce a laser damage of material. The central idea of our approach is that, instead of the ρ = ρ
c
ratio, the laser-breakdown threshold connects to the total laser energy coupled to the electron subsystem and subsequently transferred to the crystal lattice. With this approach, as we show in this work, predictions of the physical model start to converge to the available experimental data.
Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human Monoacylglycerol Lipase
Authors: Tyukhtenko Sergiy , Rajarshi Girija , Karageorgos Ioannis , Zvonok Nikolai , Gallagher Elyssia S. , Huang Hongwei , Vemuri Kiran , Hudgens Jeffrey W. , Ma Xiaoyu , Nasr Mahmoud L. , Pavlopoulos Spiro , Makriyannis Alexandros
Published: January 2018

An understanding of how conformational dynamics modulates function and catalysis of human monoacylglycerol lipase (hMGL), an important pharmaceutical target, can facilitate the development of novel ligands with potential therapeutic value. Here, we report the discovery and characterization of an allosteric, regulatory hMGL site comprised of residues Trp-289 and Leu-232 that reside over 18 Å away from the catalytic triad. These residues were identified as critical mediators of long-range communication and as important contributors to the integrity of the hMGL structure. Nonconservative replacements of Trp-289 or Leu-232 triggered concerted motions of structurally distinct regions with a significant conformational shift toward inactive states and dramatic loss in catalytic efficiency of the enzyme. Using a multimethod approach, we show that the dynamically relevant Trp-289 and Leu-232 residues serve as communication hubs within an allosteric protein network that controls signal propagation to the active site, and thus, regulates active-inactive interconversion of hMGL. Our findings provide new insights into the mechanism of allosteric regulation of lipase activity, in general, and may provide alternative drug design possibilities.
One-stage technique for sagittal split ramus osteotomy combined with mandibular angle ostectomy
Authors: Chen Shuo , Zhang Yi , An Jin-gang , He Yang
Published: January 2018

Bilateral sagittal split ramus osteotomy (BSSRO) is commonly used to correct mandibular prognathism or retrognathism. Patients with mandibular prognathism or retrognathism may also present with a prominent mandibular angle. In this paper, we share our experience on BSSRO with mandibular angle resection. Eleven patients who were treated from July 2014 to December 2016 were included in this study. The mandibular angle was resected through the medial side of the mandible after BSSRO. The mandibular angle measurements of the patients changed significantly after surgery (p < 0.05). Unanticipated fractures and mandibular hematoma did not occur. Therefore, BSSRO combined with mandibular angle ostectomy through the medial side of the mandible can be used to safely and effectively correct facial deformity.
Shape evolution of ooids: a geometric model
Authors: Sipos András A. , Domokos Gábor , Jerolmack Douglas J.
Published: January 2018

Striking shapes in nature have been documented to result from chemical precipitation — such as terraced hot springs and stromatolites — which often proceeds via surface-normal growth. Another studied class of objects is those whose shape evolves by physical abrasion — the primary example being river and beach pebbles — which results in shape-dependent surface erosion. While shapes may evolve in a self-similar manner, in neither growth nor erosion can a surface remain invariant. Here we investigate a rare and beautiful geophysical problem that combines both of these processes; the shape evolution of carbonate particles known as ooids. We hypothesize that mineral precipitation, and erosion due to wave-current transport, compete to give rise to novel and invariant geometric forms. We show that a planar (2D) mathematical model built on this premise predicts time-invariant (equilibrium) shapes that result from a balance between precipitation and abrasion. These model results produce nontrivial shapes that are consistent with mature ooids found in nature.
Mechanisms driving the antibacterial and antibiofilm properties of Hp1404 and its analogue peptides against multidrug-resistant Pseudomonas aeruginosa
Authors: Kim Min Kyung , Kang Hee Kyoung , Ko Su Jin , Hong Min Ji , Bang Jeong Kyu , Seo Chang Ho , Park Yoonkyung
Published: January 2018

Hp1404, identified from the venom of the scorpion Heterometrus petersii, displays antimicrobial activity with cytotoxicity. Several synthetic peptides were designed based on the parent peptide Hp1404 to reduce cytotoxicity and improve activity (deletion of glycine and phenylalanine, substitution with leucine and lysine). The analogue peptides generated comprised 12 amino acids and displayed amphipathic α-helical structures, with higher hydrophobic moments and net positive charge than those of the Hp1404. The analogues showed less hemolytic and toxic effects toward mammalian cells than the Hp1404, especially Hp1404-T1e, which exhibited particularly potent antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa (MRPA) strains. The analogue peptide Hp1404-T1e was more stable against salt and trypsin than the Hp1404. Hp1404’s mechanism of action involves binding to lipopolysaccharide (LPS), thereby killing bacteria through membrane disruption. Hp1404-T1e kills bacteria more rapidly than Hp1404 and not only seems to bind more strongly to LPS but may also be able to enter bacterial cells and interact with their DNA. Additionally, Hp1404-T1e can effectively kill bacteria in vivo. The results of this study indicate that Hp1404-T1e not only displays antimicrobial activity, but is also functional in physiological conditions, confirming its potential use as an effective therapeutic agent against MRPA.
3′,4′-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
Authors: Lau Yeh Siang , Mustafa Mohd Rais , Choy Ker Woon , Chan Stanley M. H. , Potocnik Simon , Herbert Terence P. , Woodman Owen L.
Published: January 2018

Endoplasmic reticulum (ER) stress has been implicated in the development of hypertension 3 through the induction of endothelial impairment. As 3′,4′-dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to attenuate ER stress, we investigated whether DiOHF can protect mice from ER stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with tunicamycin to induce ER stress in the presence or absence of either DiOHF or tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin elevated blood pressure and impaired endothelium-dependent relaxation. Moreover, in aortae there was evidence of ER stress, oxidative stress and reduced NO production. This was coincident with increased NOX2 expression and reduced phosphorylation of endothelial nitric oxide synthase (eNOS) on Ser1176. Importantly, the effects of tunicamycin were significantly ameliorated by DiOHF or TUDCA. DiOHF also inhibited tunicamycin-induced ER stress and apoptosis in cultured human endothelial cells (HUVEC). These results provide evidence that ER stress is likely an important initiator of endothelial dysfunction through the induction of oxidative stress and a reduction in NO synthesis and that DiOHF directly protects against ER stress- induced injury. DiOHF may be useful to prevent ER and oxidative stress to preserve endothelial function, for example in hypertension.
Publisher Correction: The burden and challenges of tuberculosis in China: findings from the Global Burden of Disease Study 2015
Authors: Zhu Sui , Xia Lan , Yu Shicheng , Chen Saobing , Zhang Juying
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
SPK1-transfected UCMSC has better therapeutic activity than UCMSC in the treatment of experimental autoimmune encephalomyelitis model of Multiple sclerosis
Authors: Wang Yun-Liang , Xue Peng , Xu Chun-Yang , Wang Zhen , Liu Xin-Shan , Hua Lin-Lin , Bai Hong-Ying , Zeng Zhi-Lei , Duan Hai-Feng , Li Jin-Feng
Published: January 2018

Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+ (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.
Author Correction: Orientational Mapping Augmented Sub-Wavelength Hyper-Spectral Imaging of Silk
Authors: Ryu Meguya , Balčytis Armandas , Wang Xuewen , Vongsvivut Jitraporn , Hikima Yuta , Li Jingliang , Tobin Mark J. , Juodkazis Saulius , Morikawa Junko
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Author Correction: Analytic model for the complex effective index of the leaky modes of tube-type anti-resonant hollow core fibers
Authors: Zeisberger Matthias , Schmidt Markus A.
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
Maturation of Pain Empathy from Child to Adult Shifts from Single to Multiple Neural Rhythms to Support Interoceptive Representations
Authors: Levy Jonathan , Goldstein Abraham , Pratt Maayan , Feldman Ruth
Published: January 2018

While empathy to the pain of conspecific is evolutionary-ancient and is observed in rodents and in primates, it also integrates higher-order affective representations. Yet, it is unclear whether human empathy for pain is inborn or matures during development and what neural processes underpin its maturation. Using magnetoencephalography, we monitored the brain response of children, adolescents, and adults (n = 209) to others’ pain, testing the shift from childhood to adult functioning. Results indicate that children’s vicarious empathy for pain operates via rudimentary sensory predictions involving alpha oscillations in somatosensory cortex, while adults’ response recruits advanced mechanisms of updating sensory predictions and activating affective empathy in viceromotor cortex via higher-level representations involving beta- and gamma-band activity. Our findings suggest that full-blown empathy to others’ pain emerges only in adulthood and involves a shift from sensory self-based to interoceptive other-focused mechanisms that support human altruism, maintain self-other differentiation, modulate feedback to monitor other’s state, and activate a plan of action to alleviate other’s suffering.
Inferences on specificity recognition at the Malus×domestica gametophytic self-incompatibility system
Authors: Pratas Maria I. , Aguiar Bruno , Vieira Jorge , Nunes Vanessa , Teixeira Vanessa , Fonseca Nuno A. , Iezzoni Amy , van Nocker Steve , Vieira Cristina P.
Published: January 2018

In Malus × domestica (Rosaceae) the product of each SFBB gene (the pollen component of the gametophytic self-incompatibility (GSI) system) of a S-haplotype (the combination of pistil and pollen genes that are linked) interacts with a sub-set of non-self S-RNases (the pistil component), but not with the self S-RNase. To understand how the Malus GSI system works, we identified 24 SFBB genes expressed in anthers, and determined their gene sequence in nine M. domestica cultivars. Expression of these SFBBs was not detected in the petal, sepal, filament, receptacle, style, stigma, ovary or young leaf. For all SFBBs (except SFBB15), identical sequences were obtained only in cultivars having the same S-RNase. Linkage with a particular S-RNase was further established using the progeny of three crosses. Such data is needed to understand how other genes not involved in GSI are affected by the S-locus region. To classify SFBBs specificity, the amino acids under positive selection obtained when performing intra-haplotypic analyses were used. Using this information and the previously identified S-RNase positively selected amino acid sites, inferences are made on the S-RNase amino acid properties (hydrophobicity, aromatic, aliphatic, polarity, and size), at these positions, that are critical features for GSI specificity determination.
A scalable approach to the computation of invariant measures for high-dimensional Markovian systems
Authors: Gerber Susanne , Olsson Simon , Noé Frank , Horenko Illia
Published: January 2018

The Markovian invariant measure is a central concept in many disciplines. Conventional numerical techniques for data-driven computation of invariant measures rely on estimation and further numerical processing of a transition matrix. Here we show how the quality of data-driven estimation of a transition matrix crucially depends on the validity of the statistical independence assumption for transition probabilities. Moreover, the cost of the invariant measure computation in general scales cubically with the dimension - and is usually unfeasible for realistic high-dimensional systems. We introduce a method relaxing the independence assumption of transition probabilities that scales quadratically in situations with latent variables. Applications of the method are illustrated on the Lorenz-63 system and for the molecular dynamics (MD) simulation data of the α-synuclein protein. We demonstrate how the conventional methodologies do not provide good estimates of the invariant measure based upon the available α-synuclein MD data. Applying the introduced approach to these MD data we detect two robust meta-stable states of α-synuclein and a linear transition between them, involving transient formation of secondary structure, qualitatively consistent with previous purely experimental reports.
The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF
Authors: Scabia Gaia , Barone Ilaria , Mainardi Marco , Ceccarini Giovanni , Scali Manuela , Buzzigoli Emma , Dattilo Alessia , Vitti Paolo , Gastaldelli Amalia , Santini Ferruccio , Pizzorusso Tommaso , Maffei Lamberto , Maffei Margherita
Published: January 2018

Leptin and Brain Derived Neurotrophic Factor (BDNF) pathways are critical players in body weight homeostasis. Noninvasive treatments like environmental stimulation are able to increase response to leptin and induce BDNF expression in the brain. Emerging evidences point to the antidepressant selective serotonin reuptake inhibitor Fluoxetine (FLX) as a drug with effects similar to environmental stimulation. FLX is known to impact on body weight, with mechanisms yet to be elucidated. We herein asked whether FLX affects energy balance, the leptin system and BDNF function. Adult lean male mice chronically treated with FLX showed reduced weight gain, higher energy expenditure, increased sensitivity to acute leptin, increased hypothalamic BDNF expression, associated to changes in white adipose tissue expression typical of “brownization”. In the Ntrk2tm1Ddg/J model, carrying a mutation in the BDNF receptor Tyrosine kinase B (TrkB), these effects are partially or totally reversed. Wild type obese mice treated with FLX showed reduced weight gain, increased energy output, and differently from untreated obese mice, a preserved acute response to leptin in terms of activation of the intracellular leptin transducer STAT3. In conclusion, FLX impacts on energy balance and induces leptin sensitivity and an intact TrkB function is required for these effects to take place.
Critical aggregation concentration for the formation of early Amyloid-β (1–42) oligomers
Authors: Novo Mercedes , Freire Sonia , Al-Soufi Wajih
Published: January 2018

The oligomers formed during the early steps of amyloid aggregation are thought to be responsible for the neurotoxic damage associated with Alzheimer’s disease. It is therefore of great interest to characterize this early aggregation process and the aggregates formed, especially for the most significant peptide in amyloid fibrils, Amyloid-β(1–42) (Aβ42). For this purpose, we directly monitored the changes in size and concentration of initially monomeric Aβ42 samples, using Fluorescence Correlation Spectroscopy. We found that Aβ42 undergoes aggregation only when the amount of amyloid monomers exceeds the critical aggregation concentration (cac) of about 90 nM. This spontaneous, cooperative process resembles surfactants self-assembly and yields stable micelle-like oligomers whose size (≈50 monomers, R
h
≈ 7–11 nm) and elongated shape are independent of incubation time and peptide concentration. These findings reveal essential features of in vitro amyloid aggregation, which may illuminate the complex in vivo process.
Time Course of Cultural Differences in Spatial Frequency Use for Face Identification
Authors: Estéphan Amanda , Fiset Daniel , Saumure Camille , Plouffe-Demers Marie-Pier , Zhang Ye , Sun Dan , Blais Caroline
Published: January 2018

Several previous studies of eye movements have put forward that, during face recognition, Easterners spread their attention across a greater part of their visual field than Westerners. Recently, we found that culture’s effect on the perception of faces reaches mechanisms deeper than eye movements, therefore affecting the very nature of information sampled by the visual system: that is, Westerners globally rely more than Easterners on fine-grained visual information (i.e. high spatial frequencies; SFs), whereas Easterners rely more on coarse-grained visual information (i.e. low SFs). These findings suggest that culture influences basic visual processes; however, the temporal onset and dynamics of these culture-specific perceptual differences are still unknown. Here, we investigate the time course of SF use in Western Caucasian (Canadian) and East Asian (Chinese) observers during a face identification task. Firstly, our results confirm that Easterners use relatively lower SFs than Westerners, while the latter use relatively higher SFs. More importantly, our results indicate that these differences arise as early as 34 ms after stimulus onset, and remain stable through time. Our research supports the hypothesis that Westerners and Easterners initially rely on different types of visual information during face processing.
Manipulation of Pro-Sociality and Rule-Following with Non-invasive Brain Stimulation
Authors: Gross Jörg , Emmerling Franziska , Vostroknutov Alexander , Sack Alexander T.
Published: January 2018

Decisions are often governed by rules on adequate social behaviour. Recent research suggests that the right lateral prefrontal cortex (rLPFC) is involved in the implementation of internal fairness rules (norms), by controlling the impulse to act selfishly. A drawback of these studies is that the assumed norms and impulses have to be deduced from behaviour and that norm-following and pro-sociality are indistinguishable. Here, we directly confronted participants with a rule that demanded to make advantageous or disadvantageous monetary allocations for themselves or another person. To disentangle its functional role in rule-following and pro-sociality, we divergently manipulated the rLPFC by applying cathodal or anodal transcranial direct current stimulation (tDCS). Cathodal tDCS increased participants’ rule-following, even of rules that demanded to lose money or hurt another person financially. In contrast, anodal tDCS led participants to specifically violate more often those rules that were at odds with what participants chose freely. Brain stimulation over the rLPFC thus did not simply increase or decrease selfishness. Instead, by disentangling rule-following and pro-sociality, our results point to a broader role of the rLPFC in integrating the costs and benefits of rules in order to align decisions with internal goals, ultimately enabling to flexibly adapt social behaviour.
Preferential amplification of a human mitochondrial DNA deletion in vitro and in vivo
Authors: Russell Oliver M. , Fruh Isabelle , Rai Pavandeep K. , Marcellin David , Doll Thierry , Reeve Amy , Germain Mitchel , Bastien Julie , Rygiel Karolina A. , Cerino Raffaele , Sailer Andreas W. , Lako Majlinda , Taylor Robert W. , Mueller Matthias , Lightowlers Robert N. , Turnbull Doug M. , Helliwell Stephen B.
Published: January 2018

We generated induced pluripotent stem cells (iPSCs) from patient fibroblasts to yield cell lines containing varying degrees of heteroplasmy for a m.13514 A > G mtDNA point mutation (2 lines) and for a ~6 kb single, large scale mtDNA deletion (3 lines). Long term culture of the iPSCs containing a single, large-scale mtDNA deletion showed consistent increase in mtDNA deletion levels with time. Higher levels of mtDNA heteroplasmy correlated with increased respiratory deficiency. To determine what changes occurred in deletion level during differentiation, teratomas comprising all three embryonic germ layers were generated from low (20%) and intermediate heteroplasmy (55%) mtDNA deletion clones. Regardless of whether iPSCs harbouring low or intermediate mtDNA heteroplasmy were used, the final levels of heteroplasmy in all teratoma germ layers increased to a similar high level (>60%). Thus, during human stem cell division, cells not only tolerate high mtDNA deletion loads but seem to preferentially replicate deleted mtDNA genomes. This has implications for the involvement of mtDNA deletions in both disease and ageing.
Arms race of temporal partitioning between carnivorous and herbivorous mammals
Authors: Wu Yonghua , Wang Haifeng , Wang Haitao , Feng Jiang
Published: January 2018

Reciprocal coevolutionary changes in predation and anti-predator behaviours have long been hypothesized, but evolutionary-scale evidence is rare. Here, we reconstructed the evolutionary-scale changes in the diel activity patterns of a predator-prey system (carnivorous and herbivorous mammals) based on a molecular phyloecological approach, providing evidence of long-term antagonistic coevolutionary changes in their diel activities. Our molecular reconstruction of diel activity patterns, which is supported by morphological evidence, consistently showed that carnivorous mammals were subjected to a shift from diurnality to nocturnality, while herbivorous mammals experienced a shift from nocturnality to diurnality during their evolutionary histories. A shift in the diel activity of the herbivores as a result of carnivore avoidance is hypothesized based on molecular, morphological and behavioural evidence, and our results suggest an evolutionary-scale arms race of diel activity shifts between carnivorous and herbivorous mammals.
Three-dimensional label-free imaging and analysis of Pinus pollen grains using optical diffraction tomography
Authors: Kim Geon , Lee SangYun , Shin Seungwoo , Park YongKeun
Published: January 2018

The structure of pollen grains is related to the reproductive function of the plants. Here, three-dimensional (3D) refractive index maps were obtained for individual conifer pollen grains using optical diffraction tomography (ODT). The 3D morphological features of pollen grains from pine trees were investigated using measured refractive index maps, in which distinct substructures were clearly distinguished and analyzed. Morphological and physiochemical parameters of the pollen grains were quantified from the obtained refractive index (RI) maps and used to quantitatively study the interspecific differences of pollen grains from different strains. Our results demonstrate that ODT can assess the structure of pollen grains. This label-free and rapid 3D imaging approach may provide a new platform for understanding the physiology of pollen grains.
Operation of a P300-based brain-computer interface in patients with Duchenne muscular dystrophy
Authors: Utsumi Kota , Takano Kouji , Okahara Yoji , Komori Tetsuo , Onodera Osamu , Kansaku Kenji
Published: January 2018

A brain-computer interface (BCI) or brain-machine interface is a technology that enables the control of a computer and other external devices using signals from the brain. This technology has been tested in paralysed patients, such as those with cervical spinal cord injuries or amyotrophic lateral sclerosis, but it has not been tested systematically in Duchenne muscular dystrophy (DMD), which is a severe type of muscular dystrophy due to the loss of dystrophin and is often accompanied by progressive muscle weakness and wasting. Here, we investigated the efficacy of a P300-based BCI for patients with DMD. Eight bedridden patients with DMD and eight age- and gender-matched able-bodied controls were instructed to input hiragana characters. We used a region-based, two-step P300-based BCI with green/blue flicker stimuli. EEG data were recorded, and a linear discriminant analysis distinguished the target from other non-targets. The mean online accuracy of inputted characters (accuracy for the two-step procedure) was 71.6% for patients with DMD and 80.6% for controls, with no significant difference between the patients and controls. The P300-based BCI was operated successfully by individuals with DMD in an advanced stage and these findings suggest that this technology may be beneficial for patients with this disease.
Automatic Knee Osteoarthritis Diagnosis from Plain Radiographs: A Deep Learning-Based Approach
Authors: Tiulpin Aleksei , Thevenot Jérôme , Rahtu Esa , Lehenkari Petri , Saarakkala Simo
Published: January 2018

Knee osteoarthritis (OA) is the most common musculoskeletal disorder. OA diagnosis is currently conducted by assessing symptoms and evaluating plain radiographs, but this process suffers from subjectivity. In this study, we present a new transparent computer-aided diagnosis method based on the Deep Siamese Convolutional Neural Network to automatically score knee OA severity according to the Kellgren-Lawrence grading scale. We trained our method using the data solely from the Multicenter Osteoarthritis Study and validated it on randomly selected 3,000 subjects (5,960 knees) from Osteoarthritis Initiative dataset. Our method yielded a quadratic Kappa coefficient of 0.83 and average multiclass accuracy of 66.71% compared to the annotations given by a committee of clinical experts. Here, we also report a radiological OA diagnosis area under the ROC curve of 0.93. Besides this, we present attention maps highlighting the radiological features affecting the network decision. Such information makes the decision process transparent for the practitioner, which builds better trust toward automatic methods. We believe that our model is useful for clinical decision making and for OA research; therefore, we openly release our training codes and the data set created in this study.
Alternative use of Bacillus subtilis spores: protection against environmental oxidative stress in human normal keratinocytes
Authors: Petruk Ganna , Donadio Giuliana , Lanzilli Mariamichela , Isticato Rachele , Monti Daria Maria
Published: January 2018

Inorganic trivalent arsenic is a major environmental pollutant and exposure to human results in many pathologies, including keratosis and carcinoma. Here, we analyzed the effects of B. subtilis spores on human normal keratinocytes in the presence of sodium arsenite oxidative stress. Pre-treatment of cells with spores before inducing oxidative stress was able to keep normal levels of intracellular ROS, GSH and lipid peroxidation, as well as to inhibit the activation of the MAPK cascade. Moreover, spores showed a positive effect on cell proliferation, probably due to their binding on the cell surface and the activation of intracellular catalases. We found that spores exert their protective effect by the nuclear translocation of Nrf-2, involved in the activation of stress response genes. This, in turn, resulted in a protective effect against sodium arsenite stress injury, as oxidative stress markers were reported to physiological levels when cells were stressed before incubating them with spores. Therefore, B. subtilis spores can be considered as a new agent to counteract oxidative stress on normal human keratinocytes.
Aerobic Exercise for a Duration of 90 min or Longer Per Week may Reduce the Atherogenic Index of Plasma
Authors: Shen Shiwei , Qi Huajin , He Xingxian , Lu Yun , Yang Chengjian , Li Feng , Wang Ling , Qiang Dongchang , Shui Kedong , Zhou Lin , Weng Xiaofeng , Shen Zhenhai , Wu Liuxin
Published: January 2018

The correlation between the weekly duration of aerobic exercise and atherogenic index of plasma (AIP) is still unknown. A cross-sectional study was conducted involving 27,827 middle-aged Chinese men who had health examinations in our hospital. The correlation between the duration of moderate-intensity aerobic exercise and AIP was determined. The mean AIP levels were 0.1166 ± 0.34475, 0.1167 ± 0.32637, and 0.0765 ± 0.32872 in the non-exercise (PA1), occasional exercise (PA2), and frequent exercise groups (PA3), respectively. Significantly higher AIP levels were observed in the PA1 and PA2 groups than the PA3 group, while no significant difference existed between the PA1 and PA2 groups. Physical activity significantly reduced the AIP after adjustment for age, body mass index, diastolic blood pressure, and fasting blood glucose and uric acid levels. In addition, the percentage of the population at high risk for atherosclerosis (AIP ≥ 0.21) was significantly lower in the PA3 group than the PA1 and PA2 groups. Moderate-intensity aerobic exercise at a weekly duration of 90 min or longer is associated with the reduction of AIP among middle-aged men in southeastern China.
Exploration of the role of the virulence factor ElrA during Enterococcus faecalis cell infection
Authors: Nunez Natalia , Derré-Bobillot Aurélie , Gaubert Stéphane , Herry Jean-Marie , Deschamps Julien , Wei Yu , Baranek Thomas , Si-Tahar Mustapha , Briandet Romain , Serror Pascale , Archambaud Cristel
Published: January 2018

Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E. faecalis also known as a virulence factor. ElrA was previously shown to prevent adhesion to macrophages. We show that ElrA does not inhibit the basic phagocytic process, but is able to prevent sensing and migration of macrophages toward E. faecalis. Presence or absence of FHL2, a eukaryotic partner of ElrA, does not affect the ElrA-dependent mechanism preventing macrophage migration. However, we highlight a partial contribution of FHL2 in ElrA-mediated virulence in vivo. Our results indicate that ElrA plays at least a dual role of which anti-phagocytic activity may contribute to dissemination of extracellular E. faecalis during infection.
Early modulation of intra-cortical inhibition during the observation of action mistakes
Authors: Cardellicchio Pasquale , Hilt Pauline M. , Olivier Etienne , Fadiga Luciano , D’Ausilio Alessandro
Published: January 2018

Errors while performing an action are fundamental for learning. During interaction others’ errors must be monitored and taken into account to allow joint action coordination and imitation learning. This monitoring relies on an action observation network (AON) mainly based on parietofrontal recurrent circuits. Although different studies suggest that inappropriate actions may rapidly be inhibited during execution, little is known about the modulation of the AON when an action misstep is shown. Here we used single and paired pulse transcranial magnetic stimulation to assess corticospinal excitability, intracortical facilitation and intracortical inhibition at different time intervals (120, 180, 240 ms) after the visual presentation of a motor execution error. Results show a specific and early (120 ms) decrease of intracortical inhibition likely because of a significant mismatch between the observed erroneous action and observer’s expectations. Indeed, as proposed by the top-down predictive framework, the motor system may be involved in the generation of these error signals and our data show that this mechanism could rely on the early decrease of intracortical inhibition within the corticomotor system.