bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of an experimental geoid at Deception Island, South Shetland Islands, Antarctica
Authors: Jigena Bismarck , Berrocoso Manuel , Torrecillas Cristina , Vidal Juan , Barbero Ignacio , Fernandez-Ros Alberto
Published: February 2016

Deception Island is an active volcano located in Bransfield Strait. Its volcanic activity is linked to the presence of gravity anomalies that influence the definition of the geoid. In this paper, a precise undulation geoid model (GeoiDEC14) has been computed from GPS, gravimetric and levelling measurements. GeoiDEC14 highlights local anomalies of the island that match with hot spots, such as the minimum values shown in Fumarole Bay and Whalers Bay (fumarole areas), or the maximum values found in the remains of lava at Colatinas, Black Glacier and Murature Point. Comparison of GeoiDEC14 with global models always shows negative values due to an average of 18.80 m for our model compared to 19.80–20.60 m for models such as ITSG-Grace2014s, EGM08, AIUG-Grace03s or EGM96. This difference is due to the lack of resolution of global models and to the volcanic activity on the island. To confirm the results, the same measurements were taken on nearby Livingston Island. The values of geoid undulation on this island reaffirm the lack of detail in the global geoid in the area, presenting an average of 18.90 m, similar to the average value of GeoiDEC14.
The impact and efficacy of routine pulse oximetry screening for CHD in a local hospital
Authors: Jones Andrew J. , Howarth Claire , Nicholl Richard , Mat-Ali Ezam , Knowles Rachel
Published: February 2016

Objectives

The objective of this study was to evaluate the impact and efficacy of pulse oximetry screening for CHD in a level-two neonatal unit without on-site access to paediatric echocardiography.

Methods

All neonatal unit admissions between 1 September, 2011 and 31 August, 2013 were reviewed to determine the outcomes of newborns identified by pulse oximetry screening. Record linkage with the National Congenital Heart Disease Audit allowed follow-up of newborns with a negative screening result.

Results

There were 11,233 live births during the study period, with 973 neonatal unit admissions unrelated to pulse oximetry screening. From the remaining screening population of 10,260 newborns, 23 were admitted on the basis of a screen-positive result; three of the 23 patients went on to have urgent echocardiograms, and two were found to have critical CHD. In the 21 newborns without critical CHD, an alternative diagnosis was made in 16 cases. Record linkage with the National Congenital Heart Disease Audit indicated that no newborns born in the hospital during the study period received surgery for critical CHD following negative screening. The estimated sensitivity of screening was 100% (95% confidence interval 15.81–100%) and specificity was 99.80% (95% confidence interval 99.69–99.87%), with a false-positive rate of 0.20% (95% confidence interval 0.13–0.31%).

Conclusion

The introduction of pulse oximetry screening to a hospital where paediatric echocardiography services are not available is practical, results in very few referrals to the regional paediatric cardiology centre, and detects cases of CHD that would otherwise go undiagnosed. Record linkage with a national CHD database provides a straightforward method for tracking cases of CHD that may have been missed by screening.
Italian Bipolar II vs I patients have better individual functioning, in spite of overall similar illness severity
Authors: Dell’Osso Bernardo , Dobrea Cristina , Cremaschi Laura , Buoli Massimiliano , Miller Shefali , Ketter Terence A. , Altamura A. Carlo
Published: February 2016

Introduction

Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles.

Methods

A sample of 217 outpatients withDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)–described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared.

Results

BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity.

Conclusion

BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field.
Prevalence of grade 1, 2 and 3 thinness is associated with lower socio-economic status in children in Shanghai, China
Authors: Chen Chang , Jin Zhijuan , Yang You , Jiang Fan , Jin Xingming , Huang Hong , Liu Shijian
Published: February 2016

Objective

We aimed to investigate the prevalence of grade 1, 2 and 3 thinness among Chinese children and to explore their associations with socio-economic status (SES).

Design

A population, school-based cross-sectional study using multistage, stratified cluster random sampling. Grade 1, 2 and 3 thinness, overweight, obesity and severe obesity were defined by the International Obesity Task Force BMI cut-offs.

Setting

Seven districts of Shanghai, China.

Subjects

Chinese children aged 3–12 years (n 84 075).

Results

In boys and girls, respectively, the prevalence of grade 1 thinness was 8·89 % and 11·78 %, of grade 2 thinness was 2·80 % and 3·74 %, and of grade 3 thinness was 2·23 % and 2·93 %. Compared with urban children, suburban children had higher prevalence of thinness. Children whose parent had low education had higher prevalence of grade 1, 2 and 3 thinness than those whose parent had high education. The prevalence of grade 2 and 3 thinness, obesity and severe obesity in low-SES children was higher than that in high-SES children, and the prevalence of grade 1 thinness was lower than that in high-SES children. Particular patterns of prevalence of grade 1, 2 and 3 thinness appeared in low-, middle- and high-SES children.

Conclusions

The study describes associations of SES with grade 1, 2 and 3 thinness, overweight, obesity and severe obesity in Shanghai children. The patterns of thinness and obesity in Shanghai provide further insights into BMI patterns in mega-cities in developing countries.
Prevalence and trends in the childhood dual burden of malnutrition in low- and middle-income countries, 1990–2012
Authors: Tzioumis Emma , Kay Melissa C , Bentley Margaret E , Adair Linda S
Published: February 2016

Objective

To describe trends in country- and individual-level dual burden of malnutrition in children <5 years, and age-stratified (<2 years, ≥2 years) country-level trends, in thirty-six low- and middle-income countries (LMIC).

Design

Using repeated cross-sectional nationally representative data, we calculated the prevalence of malnutrition (stunting, wasting, overweight) at each survey wave, annualized rates of prevalence change for each country over time, and trends before and after 2000, for all children <5 years and separately for those </≥2 years. We examined country- (ratio of stunting to overweight) and individual-level (coexistence of stunting and overweight) dual burden in children <5 years.

Setting

Demographic and Health Surveys from thirty-six LMIC between 1990 and 2012.

Subjects

Children <5 years.

Results

Overall malnutrition prevalence decreased in children <5 years, driven by stunting decreases. Stunting rates decreased in 78 % of countries, wasting rates decreased in 58 % of countries and overweight rates increased in 36 % of countries. Rates of change differed for children </≥2 years, with children <2 years experiencing decreases in stunting in fewer countries yet increases in overweight in more countries. Countries with nearly equal prevalences of stunting and overweight in children <5 years increased from 2000 to the final year. Within a country, 0·3–10·9 % of children <5 years were stunted and overweight, and 0·6–37·8 % of stunted children <5 years were overweight.

Conclusions

The dual burden exists in children <5 years on both country and individual levels, indicating a shift is needed in policies and programmes to address both sides of malnutrition. Children <2 years should be identified as a high-risk demographic.
The TPP and Good Regulatory Practices: An Opportunity for Regulatory Coherence to Promote Regulatory Autonomy?
Authors: SHEARGOLD ELIZABETH , MITCHELL ANDREW D.
Published: February 2016

Chapters relating to regulatory coherence or cooperation are likely to be significant features of new preferential trade agreements, including the Trans-Pacific Partnership (TPP). While the potential for harmonization of standards or institutional cooperation to impact on the regulatory autonomy of treaty parties has been well considered, this article focuses on those elements of regulatory coherence that relate to domestic processes for the development of regulations. It examines whether the adoption of ‘good regulatory practices’ in accordance with the TPP will help to ensure that measures states enact to protect non-economic interests (such as the environment or public health) are consistent with other key obligations of international trade and investment law. Although many elements of good regulatory practice mirror the criteria used to distinguish legitimate regulatory measures from disguised protectionism, there is no guarantee that a tribunal will come to the same conclusions as those reached during a domestic impact assessment.
Cost-effectiveness thresholds in health care: a bookshelf guide to their meaning and use
Authors: Culyer Anthony J.
Published: February 2016

There is misunderstanding about both the meaning and the role of cost-effectiveness thresholds in policy decision making. This article dissects the main issues by use of a bookshelf metaphor. Its main conclusions are as follows: it must be possible to compare interventions in terms of their impact on a common measure of health; mere effectiveness is not a persuasive case for inclusion in public insurance plans; public health advocates need to address issues of relative effectiveness; a ‘first best’ benchmark or threshold ratio of health gain to expenditure identifies the least effective intervention that should be included in a public insurance plan; the reciprocal of this ratio – the ‘first best’ cost-effectiveness threshold – will rise or fall as the health budget rises or falls (ceteris paribus); setting thresholds too high or too low costs lives; failure to set any cost-effectiveness threshold at all also involves avertable deaths and morbidity; the threshold cannot be set independently of the health budget; the threshold can be approached from either the demand side or the supply side – the two are equivalent only in a health-maximising equilibrium; the supply-side approach generates an estimate of a ‘second best’ cost-effectiveness threshold that is higher than the ‘first best’; the second best threshold is the one generally to be preferred in decisions about adding or subtracting interventions in an established public insurance package; multiple thresholds are implied by systems having distinct and separable health budgets; disinvestment involves eliminatingeffectivetechnologies from the insured bundle; differential weighting of beneficiaries’ health gains may affect the threshold; anonymity and identity are factors that may affect the interpretation of the threshold; the true opportunity cost of health care in a community, where the effectiveness of interventions is determined by their impact on health, is not to be measured in money – but in health itself.
Religion and Secularism among American Party Activists
Authors: Layman Geoffrey C. , Weaver Christopher L.
Published: February 2016

Prior work has shown party activists and religious divisions to be two of the leading causes of party polarization in American politics. Using the Convention Delegate Studies, we examine the interaction between these two culprits and their impact on party polarization. We leverage a novel measure of secularism in the latest wave of the Convention Delegate Studies to demonstrate that active secularism is distinct both conceptually and statistically from low religiosity. Furthermore, we show that both religiosity and secularism drive party activists to take more extreme policy positions, to identify themselves as more ideologically extreme, and to exhibit less support for compromise. As the Democratic and Republican Parties have become more secular and religious, respectively, these results suggest religious polarization may compound existing divisions between the two parties and exacerbate the partisan divide in American politics.
Super-crystals in composite ferroelectrics
Authors: Pierangeli D. , Ferraro M. , Di Mei F. , Di Domenico G. , de Oliveira C. E. M. , Agranat A. J. , DelRe E.
Published: February 2016

As atoms and molecules condense to form solids, a crystalline state can emerge with its highly ordered geometry and subnanometric lattice constant. In some physical systems, such as ferroelectric perovskites, a perfect crystalline structure forms even when the condensing substances are non-stoichiometric. The resulting solids have compositional disorder and complex macroscopic properties, such as giant susceptibilities and non-ergodicity. Here, we observe the spontaneous formation of a cubic structure in composite ferroelectric potassium–lithium–tantalate–niobate with micrometric lattice constant, 104 times larger than that of the underlying perovskite lattice. The 3D effect is observed in specifically designed samples in which the substitutional mixture varies periodically along one specific crystal axis. Laser propagation indicates a coherent polarization super-crystal that produces an optical X-ray diffractometry, an ordered mesoscopic state of matter with important implications for critical phenomena and applications in miniaturized 3D optical technologies.
Multiscale deformations lead to high toughness and circularly polarized emission in helical nacre-like fibres
Authors: Zhang Jia , Feng Wenchun , Zhang Huangxi , Wang Zhenlong , Calcaterra Heather A. , Yeom Bongjun , Hu Ping An , Kotov Nicholas A.
Published: February 2016

Nacre-like composites have been investigated typically in the form of coatings or free-standing sheets. They demonstrated remarkable mechanical properties and are used as ultrastrong materials but macroscale fibres with nacre-like organization can improve mechanical properties even further. The fiber form or nacre can, simplify manufacturing and offer new functional properties unknown yet for other forms of biomimetic materials. Here we demonstrate that nacre-like fibres can be produced by shear-induced self-assembly of nanoplatelets. The synergy between two structural motifs—nanoscale brick-and-mortar stacking of platelets and microscale twisting of the fibres—gives rise to high stretchability (>400%) and gravimetric toughness (640 J g−1). These unique mechanical properties originate from the multiscale deformation regime involving solid-state self-organization processes that lead to efficient energy dissipation. Incorporating luminescent CdTe nanowires into these fibres imparts the new property of mechanically tunable circularly polarized luminescence. The nacre-like fibres open a novel technological space for optomechanics of biomimetic composites, while their continuous spinning methodology makes scalable production realistic.
Creating single-atom Pt-ceria catalysts by surface step decoration
Authors: Dvořák Filip , Farnesi Camellone Matteo , Tovt Andrii , Tran Nguyen-Dung , Negreiros Fabio R. , Vorokhta Mykhailo , Skála Tomáš , Matolínová Iva , Mysliveček Josef , Matolín Vladimír , Fabris Stefano
Published: February 2016

Single-atom catalysts maximize the utilization of supported precious metals by exposing every single metal atom to reactants. To avoid sintering and deactivation at realistic reaction conditions, single metal atoms are stabilized by specific adsorption sites on catalyst substrates. Here we show by combining photoelectron spectroscopy, scanning tunnelling microscopy and density functional theory calculations that Pt single atoms on ceria are stabilized by the most ubiquitous defects on solid surfaces—monoatomic step edges. Pt segregation at steps leads to stable dispersions of single Pt2+ ions in planar PtO4 moieties incorporating excess O atoms and contributing to oxygen storage capacity of ceria. We experimentally control the step density on our samples, to maximize the coverage of monodispersed Pt2+ and demonstrate that step engineering and step decoration represent effective strategies for understanding and design of new single-atom catalysts.
Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability
Authors: Ngo Thuy T. M. , Yoo Jejoong , Dai Qing , Zhang Qiucen , He Chuan , Aksimentiev Aleksei , Ha Taekjip
Published: February 2016

Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility.
The role of kinetic context in apparent biased agonism at GPCRs
Authors: Klein Herenbrink Carmen , Sykes David A. , Donthamsetti Prashant , Canals Meritxell , Coudrat Thomas , Shonberg Jeremy , Scammells Peter J. , Capuano Ben , Sexton Patrick M. , Charlton Steven J. , Javitch Jonathan A. , Christopoulos Arthur , Lane J. Robert
Published: February 2016

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism.
Subnanometre enzyme mechanics probed by single-molecule force spectroscopy
Authors: Pelz Benjamin , Žoldák Gabriel , Zeller Fabian , Zacharias Martin , Rief Matthias
Published: February 2016

Enzymes are molecular machines that bind substrates specifically, provide an adequate chemical environment for catalysis and exchange products rapidly, to ensure fast turnover rates. Direct information about the energetics that drive conformational changes is difficult to obtain. We used subnanometre single-molecule force spectroscopy to study the energetic drive of substrate-dependent lid closing in the enzyme adenylate kinase. Here we show that in the presence of the bisubstrate inhibitor diadenosine pentaphosphate (AP5A), closing and opening of both lids is cooperative and tightly coupled to inhibitor binding. Surprisingly, binding of the substrates ADP and ATP exhibits a much smaller energetic drive towards the fully closed state. Instead, we observe a new dominant energetic minimum with both lids half closed. Our results, combining experiment and molecular dynamics simulations, give detailed mechanical insights into how an enzyme can cope with the seemingly contradictory requirements of rapid substrate exchange and tight closing, to ensure efficient catalysis.
Differences in the Pulsatile Component of the Skin Hemodynamic Response to Verbal Fluency Tasks in the Forehead and the Fingertip
Authors: Takahashi Toshimitsu , Takikawa Yoriko , Kawagoe Reiko
Published: February 2016

Several studies have claimed that hemodynamic signals measured by near-infrared spectroscopy (NIRS) on the forehead exhibit different patterns during a verbal fluency task (VFT) in various psychiatric disorders, whereas many studies have noted that NIRS signals can reflect task-related changes in skin blood flow. If such a task-related skin hemodynamic response is also observed in the fingertip, a simpler biomarker may be developed. Furthermore, determining the difference in the response pattern may provide physiological insights into the condition. We found that the magnitude of the pulsatile component in skin hemodynamic signals increased on the forehead (p < 0.001 for N = 50, p = 0.073 for N = 8) but decreased on the fingertip (p < 0.001, N = 8) during the VFT, whereas the rate in both areas increased (p < 0.02, N = 8). We also did not find a repetition effect in both the rate and the magnitude on the fingertip, whereas the effect was present in the magnitude (p < 0.02, N = 8) but not in the rate on the forehead. These results suggest that the skin vasomotor system in the forehead could have a different vessel mechanism to psychological tasks compared to the fingertip.
Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging
Authors: Oza Goldie , Ravichandran M. , Merupo Victor-Ishrayelu , Shinde Sachin , Mewada Ashmi , Ramirez Jose Tapia , Velumani S. , Sharon Madhuri , Sharon Maheshwar
Published: February 2016

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.
Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation
Authors: Caliari Steven R. , Perepelyuk Maryna , Cosgrove Brian D. , Tsai Shannon J. , Lee Gi Yun , Mauck Robert L. , Wells Rebecca G. , Burdick Jason A.
Published: February 2016

Tissue fibrosis contributes to nearly half of all deaths in the developed world and is characterized by progressive matrix stiffening. Despite this, nearly all in vitro disease models are mechanically static. Here, we used visible light-mediated stiffening hydrogels to investigate cell mechanotransduction in a disease-relevant system. Primary hepatic stellate cell-seeded hydrogels stiffened in situ at later time points (following a recovery phase post-isolation) displayed accelerated signaling kinetics of both early (Yes-associated protein/Transcriptional coactivator with PDZ-binding motif, YAP/TAZ) and late (alpha-smooth muscle actin, α-SMA) markers of myofibroblast differentiation, resulting in a time course similar to observed in vivo activation dynamics. We further validated this system by showing that α-SMA inhibition following substrate stiffening resulted in attenuated stellate cell activation, with reduced YAP/TAZ nuclear shuttling and traction force generation. Together, these data suggest that stiffening hydrogels may be more faithful models for studying myofibroblast activation than static substrates and could inform the development of disease therapeutics.
A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative
Authors: Mononen Mika E. , Tanska Petri , Isaksson Hanna , Korhonen Rami K.
Published: February 2016

We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group’s joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R2 = 0.95, p < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0–2 years, p < 0.001) was followed by a slow or negligible degeneration (2–4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.
Different pollinator assemblages ensure reproductive success of Cleisostoma linearilobatum (Orchidaceae) in fragmented holy hill forest and traditional tea garden
Authors: Zhou Xiang , Liu Qiang , Han Jessie Yc , Gao JiangYun
Published: February 2016

Orchids are generally recognized to have specialist pollination systems and low fruit set is often thought to be characteristic of the family. In this study, we investigated the reproductive ecology of Cleisostoma linearilobatum, an epiphytic tropical orchid, in a holy hill forest fragment and a traditional tea garden in SW China using comparable methods. C. linearilobatum is self-compatible and dependent on insects for pollination. Fruit production in natural conditions was both pollinator- and resource-limited. However, the natural fruit set remained stable over multiple years at both sites. Pollination observations showed that C. linearilobatum has a generalized pollination system and seven insect species were observed as legitimate pollinators. Although the visit frequencies of different pollinators were different in the two sites, the pollinator assemblages ensured reproductive success of C. linearilobatum in both study sites over multiple years. The results partly explain why C. linearilobatum is so successful in the area and also suggest that holy hill forest fragments and traditional tea gardens in Xishuangbanna are important in preserving orchids, especially those with generalist pollination.
Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification
Authors: Liu Ling , Liu Xu , Ren Xudong , Tian Yue , Chen Zhenyu , Xu Xiangjie , Du Yanhua , Jiang Cizhong , Fang Yujiang , Liu Zhongliang , Fan Beibei , Zhang Quanbin , Jin Guohua , Yang Xiao , Zhang Xiaoqing
Published: February 2016

The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.
The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression
Authors: de Bruin Ruben G. , van der Veer Eric P. , Prins Jurriën , Lee Dae Hyun , Dane Martijn J. C. , Zhang Huayu , Roeten Marko K. , Bijkerk Roel , de Boer Hetty C. , Rabelink Ton J. , van Zonneveld Anton Jan , van Gils Janine M.
Published: February 2016

Proper regulation of endothelial cell-cell contacts is essential for physiological functioning of the endothelium. Interendothelial junctions are actively involved in the control of vascular leakage, leukocyte diapedesis and the initiation and progression of angiogenesis. We found that the RNA-binding protein quaking is highly expressed by endothelial cells and that its expression was augmented by prolonged culture under laminar flow and the transcription factor KLF2 binding to the promoter. Moreover, we demonstrated that quaking directly binds to the mRNA of VE-cadherin and β-catenin and can induce mRNA translation mediated by the 3′UTR of these genes. Reduced quaking levels attenuated VE-cadherin and β-catenin expression and endothelial barrier function in vitro and resulted in increased bradykinin-induced vascular leakage in vivo. Taken together, we report that quaking is essential in maintaining endothelial barrier function. Our results provide novel insight into the importance of post-transcriptional regulation in controlling vascular integrity.
Erratum: Obesity changes the human gut mycobiome
Authors: Mar Rodríguez M. , Pérez Daniel , Javier Chaves Felipe , Esteve Eduardo , Marin-Garcia Pablo , Xifra Gemma , Vendrell Joan , Jové Mariona , Pamplona Reinald , Ricart Wifredo , Portero-Otin Manuel , Chacón Matilde R. , Fernández Real José Manuel
Published: February 2016

Scientific Reports 5: Article number: 14600; published online: 12 October 2015; updated: 24 February 2016. In this Article, Figure 4g is a duplication of Figure 5a. The correct Figure 4g appears below as Fig. 1.
The uncoupled ATPase activity of the ABC transporter BtuC2D2 leads to a hysteretic conformational change, conformational memory and improved activity
Authors: Livnat-Levanon Nurit , I. Gilson Amy , Ben-Tal Nir , Lewinson Oded
Published: February 2016

ABC transporters comprise a large and ubiquitous family of proteins. From bacteria to man they translocate solutes at the expense of ATP hydrolysis. Unlike other enzymes that use ATP as an energy source, ABC transporters are notorious for having high levels of basal ATPase activity: they hydrolyze ATP also in the absence of their substrate. It is unknown what are the effects of such prolonged and constant activity on the stability and function of ABC transporters or any other enzyme. Here we report that prolonged ATP hydrolysis is beneficial to the ABC transporter BtuC2D2. Using ATPase assays, surface plasmon resonance interaction experiments and transport assays we observe that the constantly active transporter remains stable and functional for much longer than the idle one. Remarkably, during extended activity the transporter undergoes a slow conformational change (hysteresis) and gradually attains a hyperactive state in which it is more active than it was to begin with. This phenomenon is different from stabilization of enzymes by ligand binding: the hyperactive state is only reached through ATP hydrolysis and not ATP binding. BtuC2D2 displays a strong conformational memory for this excited state and takes hours to return to its basal state after catalysis terminates.
Carbonate-based Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ
Authors: Guix Maria , Meyer Anne K. , Koch Britta , Schmidt Oliver G.
Published: February 2016

Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems.
Unique Loss of the PYHIN Gene Family in Bats Amongst Mammals: Implications for Inflammasome Sensing
Authors: Ahn Matae , Cui Jie , Irving Aaron T. , Wang Lin-Fa
Published: February 2016

Recent genomic analysis of two bat species (Pteropus alecto and Myotis davidii) revealed the absence of the PYHIN gene family. This family is recognized as important immune sensors of intracellular self and foreign DNA and activators of the inflammasome and/or interferon pathways. Further assessment of a wider range of bat genomes was necessary to determine if this is a universal pattern for this large mammalian group. Here we expanded genomic analysis of this gene family to include ten bat species. We confirmed the complete loss of this gene family, with only a truncated AIM2 remaining in one species (Pteronotus parnellii). Divergence of the PYHIN gene loci between the bat lineages infers different loss-of-function histories during bat evolution. While all other major groups of placental mammals have at least one gene member, only bats have lost the entire family. This removal of inflammasome DNA sensors may indicate an important adaptation that is flight-induced and related, at least in part, to pathogen-host co-existence.
Picosecond optical vortex pulse illumination forms a monocrystalline silicon needle
Authors: Takahashi Fuyuto , Miyamoto Katsuhiko , Hidai Hirofumi , Yamane Keisaku , Morita Ryuji , Omatsu Takashige
Published: February 2016

The formation of a monocrystalline silicon needle by picosecond optical vortex pulse illumination was demonstrated for the first time in this study. The dynamics of this silicon needle formation was further revealed by employing an ultrahigh-speed camera. The melted silicon was collected through picosecond pulse deposition to the dark core of the optical vortex, forming the silicon needle on a submicrosecond time scale. The needle was composed of monocrystalline silicon with the same lattice index (100) as that of the silicon substrate and had a height of approximately 14 μm and a thickness of approximately 3 μm. Overlaid vortex pulses allowed the needle to be shaped with a height of approximately 40 μm without any changes to the crystalline properties. Such a monocrystalline silicon needle can be applied to devices in many fields, such as core–shell structures for silicon photonics and photovoltaic devices as well as nano- or microelectromechanical systems.
Spin-communication channels between Ln(III) bis-phthalocyanines molecular nanomagnets and a magnetic substrate
Authors: Candini A. , Klar D. , Marocchi S. , Corradini V. , Biagi R. , De Renzi V. , del Pennino U. , Troiani F. , Bellini V. , Klyatskaya S. , Ruben M. , Kummer K. , Brookes N. B. , Huang H. , Soncini A. , Wende H. , Affronte M.
Published: February 2016

Learning the art of exploiting the interplay between different units at the atomic scale is a fundamental step in the realization of functional nano-architectures and interfaces. In this context, understanding and controlling the magnetic coupling between molecular centers and their environment is still a challenging task. Here we present a combined experimental-theoretical work on the prototypical case of the bis(phthalocyaninato)-lanthanide(III) (LnPc2) molecular nanomagnets magnetically coupled to a Ni substrate. By means of X-ray magnetic circular dichroism we show how the coupling strength can be tuned by changing the Ln ion. The microscopic parameters of the system are determined by ab-initio calculations and then used in a spin Hamiltonian approach to interpret the experimental data. By this combined approach we identify the features of the spin communication channel: the spin path is first realized by the mediation of the external (5d) electrons of the Ln ion, keeping the characteristic features of the inner 4 f orbitals unaffected, then through the organic ligand, acting as a bridge to the external world.
Expression of the innate immune receptor LILRB5 on monocytes is associated with mycobacteria exposure
Authors: Hogan Louise E. , Jones Des C. , Allen Rachel L.
Published: February 2016

Antigen presenting cells (APC) are critical components of innate immunity and consequently shape the adaptive response. Leukocyte Ig Like Receptors (LILR) are innate immune receptors predominantly expressed on myeloid cells. LILR can influence the antigen presenting phenotype of monocytic cells to determine the nature of T cell responses in infections including Mycobaterium leprae. We therefore investigated the relevance of LILR in the context of Mycobacterium tuberculosis. Real-time PCR studies indicated that the transcriptional profile of the orphan receptor LILRB5 was significantly up-regulated following exposure to mycobacteria. Furthermore, LILRA1 and LILRB5 were able to trigger signalling through direct engagement of mycobacteria using tranfectant cells incorporating a reporter system. We describe for the first time the expression of this receptor on T cells, and highlight the potential relevance to mycobacterial recognition. Furthermore, we demonstrate that crosslinking of this receptor on T cells increases proliferation of cytotoxic, but not helper, T cells.
Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis
Authors: Zhang Hongyu , Siegel Christopher T. , Shuai Ling , Lai Jiejuan , Zeng Linli , Zhang Yujun , Lai Xiangdong , Bie Ping , Bai Lianhua
Published: February 2016

NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration.
Topological Crystalline Insulator in a New Bi Semiconducting Phase
Authors: Munoz F. , Vergniory M. G. , Rauch T. , Henk J. , Chulkov E. V. , Mertig I. , Botti S. , Marques M. A. L. , Romero A. H.
Published: February 2016

Topological crystalline insulators are a type of topological insulators whose topological surface states are protected by a crystal symmetry, thus the surface gap can be tuned by applying strain or an electric field. In this paper we predict by means of ab initio calculations a new phase of Bi which is a topological crystalline insulator characterized by a mirror Chern number nM = −2, but not a "Equation missing" strong topological insulator. This system presents an exceptional property: at the (001) surface its Dirac cones are pinned at the surface high-symmetry points. As a consequence they are also protected by time-reversal symmetry and can survive against weak disorder even if in-plane mirror symmetry is broken at the surface. Taking advantage of this dual protection, we present a strategy to tune the band-gap based on a topological phase transition unique to this system. Since the spin-texture of these topological surface states reduces the back-scattering in carrier transport, this effective band-engineering is expected to be suitable for electronic and optoelectronic devices with reduced dissipation.
Protective V127 prion variant prevents prion disease by interrupting the formation of dimer and fibril from molecular dynamics simulations
Authors: Zhou Shuangyan , Shi Danfeng , Liu Xuewei , Liu Huanxiang , Yao Xiaojun
Published: February 2016

Recent studies uncovered a novel protective prion protein variant: V127 variant, which was reported intrinsically resistant to prion conversion and propagation. However, the structural basis of its protective effect is still unknown. To uncover the origin of the protective role of V127 variant, molecular dynamics simulations were performed to explore the influence of G127V mutation on two key processes of prion propagation: dimerization and fibril formation. The simulation results indicate V127 variant is unfavorable to form dimer by reducing the main-chain H-bond interactions. The simulations of formed fibrils consisting of β1 strand prove V127 variant will make the formed fibril become unstable and disorder. The weaker interaction energies between layers and reduced H-bonds number for V127 variant reveal this mutation is unfavorable to the formation of stable fibril. Consequently, we find V127 variant is not only unfavorable to the formation of dimer but also unfavorable to the formation of stable core and fibril, which can explain the mechanism on the protective role of V127 variant from the molecular level. Our findings can deepen the understanding of prion disease and may guide the design of peptide mimetics or small molecule to mimic the protective effect of V127 variant.
Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)
Authors: Liu Xiao , Li Zesong , Su Zheng , Zhang Junjie , Li Honggang , Xie Jun , Xu Hanshi , Jiang Tao , Luo Liya , Zhang Ruifang , Zeng Xiaojing , Xu Huaiqian , Huang Yi , Mou Lisha , Hu Jingchu , Qian Weiping , Zeng Yong , Zhang Xiuqing , Xiong Chengliang , Yang Huanming , Kristiansen Karsten , Cai Zhiming , Wang Jun , Gui Yaoting
Published: February 2016

Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.
3D visualization of the lumbar facet joint after degeneration using propagation phase contrast micro-tomography
Authors: Cao Yong , Zhang Yi , Yin Xianzhen , Lu Hongbin , Hu Jianzhong , Duan Chunyue
Published: February 2016

Lumbar facet joint (LFJ) degeneration is believed to be an important cause of low back pain (LBP). Identifying the morphological changes of the LFJ in the degeneration process at a high-resolution level could be meaningful for our better understanding of the possible mechanisms underlying this process. In the present study, we determined the 3D morphology of the LFJ using propagation phase contrast micro-tomography (PPCT) in rats to assess the subtle changes that occur during the degeneration process. PPCT provides vivid 3D images of micromorphological changes in the LFJ during its degeneration process, and the changes in the subchondral bone occurred earlier than in the cartilage during the early stage of degeneration of the LFJ. The delineation of this alteration was similar to that with the histological method. Our findings demonstrated that PPCT could serve as a valuable tool for 3D visualization of the morphology of the LFJ by providing comprehensive information about the cartilage and the underlying subchondral bone and their changes during degeneration processes. It might also have great potential for providing effective diagnostic tools to track changes in the cartilage and to evaluate the effects of therapeutic interventions for LFJ degeneration in preclinical studies.