bluuebunny/crossref_metadata_2025 huggingface dataset:
Early improvement in food cravings are associated with long-term weight loss success in a large clinical sample
Authors: Dalton M , Finlayson G , Walsh B , Halseth A E , Duarte C , Blundell J E
Published: April 2017

Background:

Food cravings are associated with dysregulated eating behaviour and obesity, and may impede successful weight loss attempts. Gaining control over food craving is therefore a component in the management of obesity. The current paper examined whether early changes in control over food craving (assessed using the Craving Control subscale on the Control of Eating Questionnaire (CoEQ)) was predictive of weight loss in four phase 3 clinical trials investigating a sustained-release combination of naltrexone/bupropion (NB) in obese adults. The underlying component structure of the CoEQ was also examined.

Method:

In an integrated analysis of four 56-week phase 3 clinical trials, subjects completed the CoEQ and had their body weight measured at baseline and at weeks 8, 16, 28 and 56. All analyses were conducted on subjects who had complete weight and CoEQ measurements at baseline and week 56, and had completed 56 weeks of NB (n=1310) or placebo (n=736). A latent growth curve model was used to examine whether early changes in the CoEQ subscales were associated with decreases in weight loss over time. Confirmatory factor analysis (CFA) was used to determine the psychometric properties of the CoEQ.

Results:

The factor structure of the CoEQ was consistent with previous findings with a four-factor solution being confirmed: Craving Control, Positive Mood, Craving for Sweet and Craving for Savoury with good internal consistency (Cronbach’sα=0.72–0.92). Subjects with the greatest improvement in Craving Control at week 8 exhibited a greater weight loss at week 56.

Conclusions:

These findings highlight the importance of the experience of food cravings in the treatment of obesity and support the use of the CoEQ as a psychometric tool for the measurement of food cravings in research and the pharmacological management of obesity.
The evolution of bacterial cell size: the internal diffusion-constraint hypothesis
Authors: Gallet Romain , Violle Cyrille , Fromin Nathalie , Jabbour-Zahab Roula , Enquist Brian J , Lenormand Thomas
Published: April 2017

Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski’s LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent ‘external diffusion’ theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative ‘internal diffusion-constraint’ (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.
Mechano-regulated surface for manipulating liquid droplets
Authors: Tang Xin , Zhu Pingan , Tian Ye , Zhou Xuechang , Kong Tiantian , Wang Liqiu
Published: April 2017

The effective transfer of tiny liquid droplets is vital for a number of processes such as chemical and biological microassays. Inspired by the tarsi of meniscus-climbing insects, which can climb menisci by deforming the water/air interface, we developed a mechano-regulated surface consisting of a background mesh and a movable microfibre array with contrastive wettability. The adhesion of this mechano-regulated surface to liquid droplets can be reversibly switched through mechanical reconfiguration of the microfibre array. The adhesive force can be tuned by varying the number and surface chemistry of the microfibres. The in situ adhesion of the mechano-regulated surface can be used to manoeuvre micro-/nanolitre liquid droplets in a nearly loss-free manner. The mechano-regulated surface can be scaled up to handle multiple droplets in parallel. Our approach offers a miniaturized mechano-device with switchable adhesion for handling micro-/nanolitre droplets, either in air or in a fluid that is immiscible with the droplets.
Remarkable catalytic activity of dinitrogen-bridged dimolybdenum complexes bearing NHC-based PCP-pincer ligands toward nitrogen fixation
Authors: Eizawa Aya , Arashiba Kazuya , Tanaka Hiromasa , Kuriyama Shogo , Matsuo Yuki , Nakajima Kazunari , Yoshizawa Kazunari , Nishibayashi Yoshiaki
Published: April 2017

Intensive efforts for the transformation of dinitrogen using transition metal–dinitrogen complexes as catalysts under mild reaction conditions have been made. However, limited systems have succeeded in the catalytic formation of ammonia. Here we show that newly designed and prepared dinitrogen-bridged dimolybdenum complexes bearingN-heterocyclic carbene- and phosphine-based PCP-pincer ligands [{Mo(N2)2(PCP)}2(μ-N2)] (1) work as so far the most effective catalysts towards the formation of ammonia from dinitrogen under ambient reaction conditions, where up to 230 equiv. of ammonia are produced based on the catalyst. DFT calculations on1reveal that the PCP-pincer ligand serves as not only a strongσ-donor but also aπ-acceptor. These electronic properties are responsible for a solid connection between the molybdenum centre and the pincer ligand, leading to the enhanced catalytic activity for nitrogen fixation.
Human seizures couple across spatial scales through travelling wave dynamics
Authors: Martinet L-E , Fiddyment G. , Madsen J. R. , Eskandar E. N. , Truccolo W. , Eden U. T. , Cash S. S. , Kramer M. A.
Published: April 2017

Epilepsy—the propensity toward recurrent, unprovoked seizures—is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms—namely, the effects of an increased extracellular potassium concentration diffusing in space—that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures—and connecting these dynamics to specific biological mechanisms—promises new insights to treat this devastating disease.
Quantitative 3D analysis of complex single border cell behaviors in coordinated collective cell migration
Authors: Cliffe Adam , Doupé David P. , Sung HsinHo , Lim Isaac Kok Hwee , Ong Kok Haur , Cheng Li , Yu Weimiao
Published: April 2017

Understanding the mechanisms of collective cell migration is crucial for cancer metastasis, wound healing and many developmental processes. Imaging a migrating cluster in vivo is feasible, but the quantification of individual cell behaviours remains challenging. We have developed an image analysis toolkit, CCMToolKit, to quantify the Drosophila border cell system. In addition to chaotic motion, previous studies reported that the migrating cells are able to migrate in a highly coordinated pattern. We quantify the rotating and running migration modes in 3D while also observing a range of intermediate behaviours. Running mode is driven by cluster external protrusions. Rotating mode is associated with cluster internal cell extensions that could not be easily characterized. Although the cluster moves slower while rotating, individual cells retain their mobility and are in fact slightly more active than in running mode. We also show that individual cells may exchange positions during migration.
IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population
Authors: Nascimento Daniele C. , Melo Paulo H. , Piñeros Annie R. , Ferreira Raphael G. , Colón David F. , Donate Paula B. , Castanheira Fernanda V. , Gozzi Aline , Czaikoski Paula G. , Niedbala Wanda , Borges Marcos C. , Zamboni Dario S. , Liew Foo Y. , Cunha Fernando Q. , Alves-Filho Jose C.
Published: April 2017

Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.
Quinuclidinium salt ferroelectric thin-film with duodecuple-rotational polarization-directions
Authors: You Yu-Meng , Tang Yuan-Yuan , Li Peng-Fei , Zhang Han-Yue , Zhang Wan-Ying , Zhang Yi , Ye Heng-Yun , Nakamura Takayoshi , Xiong Ren-Gen
Published: April 2017

Ferroelectric thin-films are highly desirable for their applications on energy conversion, data storage and so on. Molecular ferroelectrics had been expected to be a better candidate compared to conventional ferroelectric ceramics, due to its simple and low-cost film-processability. However, most molecular ferroelectrics are mono-polar-axial, and the polar axes of the entire thin-film must be well oriented to a specific direction to realize the macroscopic ferroelectricity. To align the polar axes, an orientation-controlled single-crystalline thin-film growth method must be employed, which is complicated, high-cost and is extremely substrate-dependent. In this work, we discover a new molecular ferroelectric of quinuclidinium periodate, which possesses six-fold rotational polar axes. The multi-axes nature allows the thin-film of quinuclidinium periodate to be simply prepared on various substrates including flexible polymer, transparent glasses and amorphous metal plates, without considering the crystallinity and crystal orientation. With those benefits and excellent ferroelectric properties, quinuclidinium periodate shows great potential in applications like wearable devices, flexible materials, bio-machines and so on.
Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior
Authors: Leclercq Sophie , Mian Firoz M. , Stanisz Andrew M. , Bindels Laure B. , Cambier Emmanuel , Ben-Amram Hila , Koren Omry , Forsythe Paul , Bienenstock John
Published: April 2017

There is increasing concern about potential long-term effects of antibiotics on children’s health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.
A phase field model for snow crystal growth in three dimensions
Authors: Demange Gilles , Zapolsky Helena , Patte Renaud , Brunel Marc
Published: April 2017

Snowflake growth provides a fascinating example of spontaneous pattern formation in nature. Attempts to understand this phenomenon have led to important insights in non-equilibrium dynamics observed in various active scientific fields, ranging from pattern formation in physical and chemical systems, to self-assembly problems in biology. Yet, very few models currently succeed in reproducing the diversity of snowflake forms in three dimensions, and the link between model parameters and thermodynamic quantities is not established. Here, we report a modified phase field model that describes the subtlety of the ice vapour phase transition, through anisotropic water molecules attachment and condensation, surface diffusion, and strong anisotropic surface tension, that guarantee the anisotropy, faceting and dendritic growth of snowflakes. We demonstrate that this model reproduces the growth dynamics of the most challenging morphologies of snowflakes from the Nakaya diagram. We find that the growth dynamics of snow crystals matches the selection theory, consistently with previous experimental observations.
Quantum parameter estimation with general dynamics
Authors: Yuan Haidong , Fung Chi-Hang Fred
Published: April 2017

One of the main quests in quantum metrology, and quantum parameter estimation in general, is to find out the highest achievable precision with given resources and design schemes to attain it. In this article we present a general framework for quantum parameter estimation and provide systematic methods for computing the ultimate precision limit, which is more general and efficient than conventional methods.
TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
Authors: Wallmeyer Leonie , Dietert Kristina , Sochorová Michaela , Gruber Achim D. , Kleuser Burkhard , Vávrová Kateřina , Hedtrich Sarah
Published: April 2017

Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4+ T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.
3D field-shaping lens using all-dielectric gradient refractive index materials
Authors: Ding Tongyu , Yi Jianjia , Li Haoyu , Zhang Hailin , Burokur Shah Nawaz
Published: April 2017

A novel three-dimensional (3D) optical lens structure for electromagnetic field shaping based on spatial light transformation method is proposed at microwave frequencies. The lens is capable of transforming cylindrical wavefronts into planar ones, and generating a directive emission. Such manipulation is simulated and analysed by solving Laplace’s equation, and the deformation of the medium during the transformation is theoretically described in detail. The two-dimensional (2D) design method producing quasi-isotropic parameters is further extended to a potential 3D realization with all-dielectric gradient refractive index metamaterials. Numerical full-wave simulations are performed on both 2D and 3D models to verify the functionality and broadband characteristics of the calculated lens. Far-field radiation patterns and near-field distributions demonstrate a highly radiated directive beam when the lens is applied to a conical horn antenna.
Phase heterogeneity in carbonate production by marine fish influences their roles in sediment generation and the inorganic carbon cycle
Authors: Salter Michael A. , Harborne Alastair R. , Perry Chris T. , Wilson Rod W.
Published: April 2017

Marine teleost fish are important carbonate producers in neritic and oceanic settings. However, the fates of the diverse carbonate phases (i.e., mineral and amorphous forms of CaCO3) they produce, and their roles in sediment production and marine inorganic carbon cycling, remain poorly understood. Here we quantify the carbonate phases produced by 22 Bahamian fish species and integrate these data with regional fish biomass data from The Bahamas to generate a novel platform-scale production model that resolves these phases. Overall carbonate phase proportions, ordered by decreasing phase stability, are: ~20% calcite, ~6% aragonite, ~60% high-Mg calcite, and ~14% amorphous carbonate. We predict that these phases undergo differing fates, with at least ~14% (amorphous carbonate) likely dissolving rapidly. Results further indicate that fisheries exploitation in The Bahamas has potentially reduced fish carbonate production by up to 58% in certain habitats, whilst also driving a deviation from natural phase proportions. These findings have evident implications for understanding sedimentary processes in shallow warm-water carbonate provinces. We further speculate that marked phase heterogeneity may be a hitherto unrecognised feature of fish carbonates across a wide range of neritic and oceanic settings, with potentially major implications for understanding their role in global marine inorganic carbon cycling.
Social media reveal that charismatic species are not the main attractor of ecotourists to sub-Saharan protected areas
Authors: Hausmann Anna , Toivonen Tuuli , Heikinheimo Vuokko , Tenkanen Henrikki , Slotow Rob , Di Minin Enrico
Published: April 2017

Charismatic megafauna are arguably considered the primary attractor of ecotourists to sub-Saharan African protected areas. However, the lack of visitation data across the whole continent has thus far prevented the investigation of whether charismatic species are indeed a key attractor of ecotourists to protected areas. Social media data can now be used for this purpose. We mined data from Instagram, and used generalized linear models with site- and country-level deviations to explore which socio-economic, geographical and biological factors explain social media use in sub-Saharan African protected areas. We found that charismatic species richness did not explain social media usage. On the other hand, protected areas that were more accessible, had sparser vegetation, where human population density was higher, and that were located in wealthier countries, had higher social media use. Interestingly, protected areas with lower richness in non-charismatic species had more users. Overall, our results suggest that more factors than simply charismatic species might explain attractiveness of protected areas, and call for more in-depth content analysis of the posts. With African countries projected to develop further in the near-future, more social media data will become available, and could be used to inform protected area management and marketing.
Association between education and the risk of incident coronary heart disease among middle-aged and older Chinese: the Dongfeng-Tongji Cohort
Authors: Wang Hao , Yuan Yu , Song Lulu , Qiu Gaokun , Lai Xuefeng , Yang Liangle , Xiao Yang , Zhou Lue , Yang Handong , Li Xiulou , Xu Chengwei , Zhang Xiaomin , He Mei-an , Wu Tangchun
Published: April 2017

Educational achievement was related to cardiovascular disease in some western populations, but prospective evidence on the relationship between education and the risk of incident coronary heart disease (CHD) in Asians is scarce. We aimed to explore this association and the potential modifying effect of major CHD risk factors related to education in middle-aged and older Chinese adults. We included 18,551 participants with mean age 62.8 years at baseline between September 2008 and June 2010, and followed the population until October 2013. Cox proportional hazard models and log-binomial regression models were used for multivariate analyses. Compared with participants with low education, the adjusted hazard ratio (HR) and 95% confidence interval (95% CI) for incident CHD in those with high education was 0.89 (95% CI: 0.80, 0.98). In addition, such inverse association between education and the risk of incident CHD was more evident among individuals who were more than 60 years, physically active, overweight, and hypertension. Besides, decreases in the relative index of inequality with high education versus low education were from 0.83 to 0.76 for hypertension, from 0.85 to 0.82 for diabetes. In conclusion, education was inversely associated with the risk of incident CHD among middle-aged and older Chinese adults.
Modulation of glucose metabolism by a natural compound from Chloranthus japonicus via activation of AMP-activated protein kinase
Authors: Hu Rongkuan , Yan Huan , Fei Xiaoyan , Liu Haiyang , Wu Jiarui
Published: April 2017

AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose metabolism. Here, we demonstrated that shizukaol F, a natural compound isolated from Chloranthus japonicus, can activate AMPK and modulate glucose metabolism both in vitro and in vivo. Shizukaol F increased glucose uptake in differentiated C2C12 myotubes by stimulating glucose transporter-4 (GLUT-4) membraned translocation. Treatment of primary mouse hepatocytes with shizukaol F decreased the expression of phosphoenolpyruvate carboxykinase 2 (PEPCK), glucose-6-phosphatase (G6Pase) and suppressed hepatic gluconeogenesis. Meanwhile, a single oral dose of shizukaol F reduced gluconeogenesis in C57BL/6 J mice. Further studies indicated that shizukaol F modulates glucose metabolism mainly by AMPKa phosphorylation activity. In addition, we also found that shizukaol F depolarizes the mitochondrial membrane and inhibits respiratory complex I, which may result in AMPK activation. Our results highlight the potential value of shizukaol F as a possible treatment of metabolic syndrome.
Impacts of the removal of shrubs on the physiological and biochemical characteristics of Syntrichia caninervis Mitt: in a temperate desert
Authors: Yin Ben-feng , Zhang Yuan-ming , Lou An-ru
Published: April 2017

Moss crusts play important roles in biological soil crusts biomass and soil surface stabilization. However, because of increasingly intensive human activities, especially grazing, the growth and survival of shrubs are seriously threatened. This study aimed to test whether the presence of shrubs affects the physiological state of the bryophyte Syntrichia caninervis Mitt. in this desert ecosystem. We simulated animal-grazed shrubs at three levels in the Gurbantunggut Desert and compared these simulations to exposed areas, measuring the indicators of growth and stress tolerance exhibited by bryophytes. The results showed that the removal of shrubs significantly decreased chlorophyll fluorescence activity and soluble protein content in S. caninervis, especially under the total shrub removal treatment. The ratio between the total removal of shrubs and other treatments in antioxidative enzymes and in osmotic adjustment substances of S. caninervis exhibited two types of responses. With the exception of malonyldialdehyde (MDA) and superoxide dismutase (SOD), the variables examined fitted as downward parabolic then upward parabolic temporal dynamics. The removal of shrubs is harmful to the survival of S.caninervis. In resource-constrained conditions, SOD is an important antioxidant enzyme that of peroxidase (POD), catalase (CAT) and osmotic adjustment substances, for S. caninervis survival.
Weakly-coupled quasi-1D helical modes in disordered 3D topological insulator quantum wires
Authors: Dufouleur J. , Veyrat L. , Dassonneville B. , Xypakis E. , Bardarson J. H. , Nowka C. , Hampel S. , Schumann J. , Eichler B. , Schmidt O. G. , Büchner B. , Giraud R.
Published: April 2017

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi2Te3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder.
Evolution of opto-electronic properties during film formation of complex semiconductors
Authors: Heinemann M. D. , Mainz R. , Österle F. , Rodriguez-Alvarez H. , Greiner D. , Kaufmann C. A. , Unold T.
Published: April 2017

Optical and electrical properties of complex semiconducting alloys like Cu(In,Ga)Se2 (CIGS) are strongly influenced by the reaction pathways occurring during their deposition process. This makes it desirable to observe and control these properties in real-time during the deposition. Here we show for the first time the evolution of the band gap and the sub-band-gap defect absorption of CIGS thin film as well as surface roughness during a three-stage co-evaporation process by means of an optical analysis technique, based on white light reflectometry (WLR). By simultaneously recording structural information with in-situ energy dispersive X-ray diffraction and X-ray fluorescence we can directly correlate the evolution of opto-electronic material parameters with the structural properties of the film during growth. We find that the surface roughness and the sub-gap light absorption can be correlated with the phase evolution during the transformation from (In,Ga)2Se3 to Cu(In,Ga)Se2 by the incorporation of Cu into the film. Sub-bandgap light absorption is found to be influenced by the Cu-saturated growth phase and is lowered close to the points of stoichiometry, allowing for an advanced process design.
Dynamic metabolic profiling together with transcription analysis reveals salinity-induced starch-to-lipid biosynthesis in alga Chlamydomonas sp. JSC4
Authors: Ho Shih-Hsin , Nakanishi Akihito , Kato Yuichi , Yamasaki Hiroaki , Chang Jo-Shu , Misawa Naomi , Hirose Yuu , Minagawa Jun , Hasunuma Tomohisa , Kondo Akihiko
Published: April 2017

Biodiesel production using microalgae would play a pivotal role in satisfying future global energy demands. Understanding of lipid metabolism in microalgae is important to isolate oleaginous strain capable of overproducing lipids. It has been reported that reducing starch biosynthesis can enhance lipid accumulation. However, the metabolic mechanism controlling carbon partitioning from starch to lipids in microalgae remains unclear, thus complicating the genetic engineering of algal strains. We here used “dynamic” metabolic profiling and essential transcription analysis of the oleaginous green alga Chlamydomonas sp. JSC4 for the first time to demonstrate the switching mechanisms from starch to lipid synthesis using salinity as a regulator, and identified the metabolic rate-limiting step for enhancing lipid accumulation (e.g., pyruvate-to-acetyl-CoA). These results, showing salinity-induced starch-to-lipid biosynthesis, will help increase our understanding of dynamic carbon partitioning in oleaginous microalgae. Moreover, we successfully determined the changes of several key lipid-synthesis-related genes (e.g., acetyl-CoA carboxylase, pyruvate decarboxylase, acetaldehyde dehydrogenase, acetyl-CoA synthetase and pyruvate ferredoxin oxidoreductase) and starch-degradation related genes (e.g., starch phosphorylases), which could provide a breakthrough in the marine microalgal production of biodiesel.
Claudin expression in the rat endolymphatic duct and sac - first insights into regulation of the paracellular barrier by vasopressin
Authors: Runggaldier Daniel , Pradas Lidia Garcia , Neckel Peter H. , Mack Andreas F. , Hirt Bernhard , Gleiser Corinna
Published: April 2017

Hearing and balance functions of the inner ear rely on the homeostasis of the endolymphatic fluid. When disturbed, pathologic endolymphatic hydrops evolves as observed in Menière’s disease. The molecular basis of inner ear fluid regulation across the endolymphatic epithelium is largely unknown. In this study we identified the specific expression of the tight junction (TJ) molecules Claudin 3, 4, 6, 7, 8, 10, and 16 in epithelial preparations of the rat inner ear endolymphatic duct (ED) and endolymphatic sac (ES) by high-throughput qPCR and immunofluorescence confocal microscopy. Further we showed that Claudin 4 in the ES is a target of arginine-vasopressin (AVP), a hormone elevated in Menière’s disease. Moreover, our transmission-electron microscopy (TEM) analysis revealed that the TJs of the ED were shallow and shorter compared to the TJ of the ES indicating facilitation of a paracellular fluid transport across the ED epithelium. The significant differences in the subcellular localization of the barrier-forming protein Claudin 3 between the ED and ES epithelium further support the TEM observations. Our results indicate a high relevance of Claudin 3 and Claudin 4 as important paracellular barrier molecules in the ED and ES epithelium with potential involvement in the pathophysiology of Menière’s disease.
A Gate Hinge Controls the Epithelial Calcium Channel TRPV5
Authors: van der Wijst Jenny , Leunissen Elizabeth H. , Blanchard Maxime G. , Venselaar Hanka , Verkaart Sjoerd , Paulsen Candice E. , Bindels René J. , Hoenderop Joost G.
Published: April 2017

TRPV5 is unique within the large TRP channel family for displaying a high Ca2+ selectivity together with Ca2+-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonstrates that W583 is part of the gate for Ca2+ permeation. The W583 mutants show increased cell death due to profoundly enhanced Ca2+ influx, resulting from altered channel function. A glycine residue above W583 might act as flexible linker to rearrange the tryptophan gate. Furthermore, we hypothesize functional crosstalk between the pore region and carboxy terminus, involved in Ca2+-calmodulin-mediated inactivation. This study proposes a unique channel gating mechanism and delivers detailed molecular insight into the Ca2+ permeation pathway that can be extrapolated to other Ca2+-selective channels.
Giant Magnetoresistive Biosensors for Time-Domain Magnetorelaxometry: A Theoretical Investigation and Progress Toward an Immunoassay
Authors: Huang Chih-Cheng , Zhou Xiahan , Hall Drew A.
Published: April 2017

Magnetorelaxometry (MRX) is a promising new biosensing technique for point-of-care diagnostics. Historically, magnetic sensors have been primarily used to monitor the stray field of magnetic nanoparticles bound to analytes of interest for immunoassays and flow cytometers. In MRX, the magnetic nanoparticles (MNPs) are first magnetized and then the temporal response is monitored after removing the magnetic field. This new sensing modality is insensitive to the magnetic field homogeneity making it more amenable to low-power portable applications. In this work, we systematically investigated time-domain MRX by measuring the signal dependence on the applied field, magnetization time, and magnetic core size. The extracted characteristic times varied for different magnetic MNPs, exhibiting unique magnetic signatures. We also measured the signal contribution based on the MNP location and correlated the coverage with measured signal amplitude. Lastly, we demonstrated, for the first time, a GMR-based time-domain MRX bioassay. This approach validates the feasibility of immunoassays using GMR-based MRX and provides an alternative platform for point-of-care diagnostics.
Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography
Authors: Lemoine Laetitia , Saint-Aubert Laure , Nennesmo Inger , Gillberg Per-Göran , Nordberg Agneta
Published: April 2017

Hyperphosphorylated tau protein deposits and, inflammatory processes are characteristic components of Alzheimer disease (AD) pathology. We here aimed to visualize in vitro the distribution of tau deposits and activated astrocytes across the cortical layers in autopsy AD brain tissue using the radiotracers 3H-THK5117 and 3H-deprenyl. 3H-THK5117 and 3H-deprenyl autoradiographies were carried out on frozen brain sections from three AD patients and one healthy control. 3H-THK5117 showed a distinct laminar cortical binding similar to 3H-deprenyl autoradiography, with an extensive binding in the superficial and deep layers of the temporal neocortices, whereas the middle frontal gyrus showed an even binding throughout the layers. Globally, eventhough some differences could be observed, AT8 (tau) and GFAP (astrocyte) immunostaining showed a laminar pattern comparable to their corresponding radiotracers within each AD case. Some variability was observed between the AD cases reflecting differences in disease phenotype. The similar laminar cortical brain distribution of tau deposits and activated astrocytes supports the hypothesis of a close pathological interconnection. The difference in regional binding patterns of 3H-THK5117 and AT8 antibody staining suggest additional tau binding sites detectable by 3H-THK5117.
Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk
Authors: Suchon P. , Germain M. , Delluc A. , Smadja D. , Jouven X. , Gyorgy B. , Saut N. , Ibrahim M. , Deleuze J. F. , Alessi M. C. , Morange P. E. , Trégouët D. A.
Published: April 2017

Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06–10.64] (p = 1.73 10−14). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10−6, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.
Atomic structure and electronic properties of MgO grain boundaries in tunnelling magnetoresistive devices
Authors: Bean Jonathan J. , Saito Mitsuhiro , Fukami Shunsuke , Sato Hideo , Ikeda Shoji , Ohno Hideo , Ikuhara Yuichi , McKenna Keith P.
Published: April 2017

Polycrystalline metal oxides find diverse applications in areas such as nanoelectronics, photovoltaics and catalysis. Although grain boundary defects are ubiquitous their structure and electronic properties are very poorly understood since it is extremely challenging to probe the structure of buried interfaces directly. In this paper we combine novel plan-view high-resolution transmission electron microscopy and first principles calculations to provide atomic level understanding of the structure and properties of grain boundaries in the barrier layer of a magnetic tunnel junction. We show that the highly [001] textured MgO films contain numerous tilt grain boundaries. First principles calculations reveal how these grain boundaries are associated with locally reduced band gaps (by up to 3 eV). Using a simple model we show how shunting a proportion of the tunnelling current through grain boundaries imposes limits on the maximum magnetoresistance that can be achieved in devices.
The classical correlation limits the ability of the measurement-induced average coherence
Authors: Zhang Jun , Yang Si-ren , Zhang Yang , Yu Chang-shui
Published: April 2017

Coherence is the most fundamental quantum feature in quantum mechanics. For a bipartite quantum state, if a measurement is performed on one party, the other party, based on the measurement outcomes, will collapse to a corresponding state with some probability and hence gain the average coherence. It is shown that the average coherence is not less than the coherence of its reduced density matrix. In particular, it is very surprising that the extra average coherence (and the maximal extra average coherence with all the possible measurements taken into account) is upper bounded by the classical correlation of the bipartite state instead of the quantum correlation. We also find the sufficient and necessary condition for the null maximal extra average coherence. Some examples demonstrate the relation and, moreover, show that quantum correlation is neither sufficient nor necessary for the nonzero extra average coherence within a given measurement. In addition, the similar conclusions are drawn for both the basis-dependent and the basis-free coherence measure.
Model-independent particle species disentanglement by X-ray cross-correlation scattering
Authors: Pedrini B. , Menzel A. , Guzenko V. A. , David C. , Abela R. , Gutt C.
Published: April 2017

Mixtures of different particle species are often investigated using the angular averages of the scattered X-ray intensity. The number of species is deduced by singular value decomposition methods. The full disentanglement of the data into per-species contributions requires additional knowledge about the system under investigation. We propose to exploit higher-order angular X-ray intensity correlations with a new computational protocol, which we apply to synchrotron data from two-species mixtures of two-dimensional static test nanoparticles. Without any other information besides the correlations, we demonstrate the assessment of particle species concentrations in the measured data sets, as well as the full ab initio reconstruction of both particle structures. The concept extends straightforwardly to more species and to the three-dimensional case, whereby the practical application will require the measurements to be performed at an X-ray free electron laser.
Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device
Authors: Qasaimeh Mohammad A. , Wu Yichao C. , Bose Suman , Menachery Anoop , Talluri Srikanth , Gonzalez Gabriel , Fulciniti Mariateresa , Karp Jeffrey M. , Prabhala Rao H. , Karnik Rohit
Published: April 2017

The necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40–70%, permitting detection of <10 CPCs/mL using 1-mL sample volumes, which is difficult using existing techniques. In bone marrow samples, the microfluidic-based plasma cell counts exhibited excellent correlation with flow cytometry analysis. In peripheral blood samples, the device detected a baseline of 2–5 CD138+ cells/mL in healthy donor blood, with significantly higher numbers in blood samples of MM patients in remission (20–24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45–184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.
Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection
Authors: Sakurai Fuminori , Mitani Seiji , Yamamoto Tatsuro , Takayama Kazuo , Tachibana Masashi , Watashi Koichi , Wakita Takaji , Iijima Sayuki , Tanaka Yasuhito , Mizuguchi Hiroyuki
Published: April 2017

In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a usefulin vitrocell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existingin vitroHBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as anin vitroHBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs. The mRNA levels of these genes were comparable between primary human hepatocytes (PHHs) and iPS-HLCs. Following inoculation with HBV, we found significant production of HBV proteins and viral RNAs in iPS-HLCs. The three major forms of the HBV genome were detected in iPS-HLCs by Southern blotting analysis. Anti-HBV agents entecavir and Myrcludex-B, which are a nucleoside analogue reverse transcriptase inhibitor and a synthetic pre-S1 peptide, respectively, significantly inhibited HBV infection in iPS-HLCs. These data demonstrate that iPS-HLCs can be used as a promisingin vitroHBV infection model.
Signatures of a macroscopic switching transition for a dynamic microtubule
Authors: Aparna J. S. , Padinhateeri Ranjith , Das Dibyendu
Published: April 2017

Characterising complex kinetics of non-equilibrium self-assembly of bio-filaments is of general interest. Dynamic instability in microtubules, consisting of successive catastrophes and rescues, is observed to occur as a result of the non-equilibrium conversion of GTP-tubulin to GDP-tubulin. We study this phenomenon using a model for microtubule kinetics with GTP/GDP state-dependent polymerisation, depolymerisation and hydrolysis of subunits. Our results reveal a sharp switch-like transition in the mean velocity of the filaments, from a growth phase to a shrinkage phase, with an associated co-existence of the two phases. This transition is reminiscent of the discontinuous phase transition across the liquid-gas boundary. We probe the extent of discontinuity in the transition quantitatively using characteristic signatures such as bimodality in velocity distribution, variance and Binder cumulant, and also hysteresis behaviour of the system. We further investigate ageing behaviour in catastrophes of the filament, and find that the multi-step nature of catastrophes is intensified in the vicinity of the switching transition. This assumes importance in the context of Microtubule Associated Proteins which have the potential of altering kinetic parameter values.
Identification of conserved proteins from diverse shell matrix proteome in Crassostrea gigas: characterization of genetic bases regulating shell formation
Authors: Feng Dandan , Li Qi , Yu Hong , Kong Lingfeng , Du Shaojun
Published: April 2017

The calcifying shell is an excellent model for studying biomineralization and evolution. However, the molecular mechanisms of shell formation are only beginning to be elucidated in Mollusca. It is known that shell matrix proteins (SMPs) play important roles in shell formation. With increasing data of shell matrix proteomes from various species, we carried out a BLASTp bioinformatics analysis using the shell matrix proteome from Crassostrea gigas against 443 SMPs from nine other species. The highly conserved tyrosinase and chitin related proteins were identified in bivalve. In addition, the relatively conserved proteins containing domains of carbonic anhydrase, Sushi, Von Willebrand factor type A, and chitin binding, were identified from all the ten species. Moreover, 25 genes encoding SMPs were annotated and characterized that are involved in CaCO3 crystallization and represent chitin related or ECM related proteins. Together, data from these analyses provide new knowledge underlying the molecular mechanism of shell formation in C.gigas, supporting a refined shell formation model including chitin and ECM-related proteins.
The impact of deep-tier burrow systems in sediment mixing and ecosystem engineering in early Cambrian carbonate settings
Authors: Zhang Li-Jun , Qi Yong-An , Buatois Luis A. , Mángano M. Gabriela , Meng Yao , Li Da
Published: April 2017

Bioturbation plays a substantial role in sediment oxygen concentration, chemical cycling, regeneration of nutrients, microbial activity, and the rate of organic matter decomposition in modern oceans. In addition, bioturbators are ecosystem engineers which promote the presence of some organisms, while precluding others. However, the impact of bioturbation in deep time remains controversial and limited sediment mixing has been indicated for early Paleozoic seas. Our understanding of the actual impact of bioturbation early in the Phanerozoic has been hampered by the lack of detailed analysis of the functional significance of specific burrow architectures. Integration of ichnologic and sedimentologic evidence from North China shows that deep-tierThalassinoidesmazes occur in lower Cambrian nearshore carbonate sediments, leading to intense disruption of the primary fabric. Comparison with modern studies suggest that some of the effects of this style of Cambrian bioturbation may have included promotion of nitrogen and ammonium fluxes across the sediment-water interface, average deepening of the redox discontinuity surface, expansion of aerobic bacteria, and increase in the rate of organic matter decomposition and the regeneration of nutrients. Our study suggests that early Cambrian sediment mixing in carbonate settings may have been more significant than assumed in previous models.