bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective association between cancer risk and an individual dietary index based on the British Food Standards Agency Nutrient Profiling System
Authors: Donnenfeld Mathilde , Julia Chantal , Kesse-Guyot Emmanuelle , Méjean Caroline , Ducrot Pauline , Péneau Sandrine , Deschasaux Mélanie , Latino-Martel Paule , Fezeu Léopold , Hercberg Serge , Touvier Mathilde
Published: September 2015

The Food Standards Agency Nutrient Profiling System (FSA-NPS) constitutes the basis for the Five-Colour Nutrition Label suggested in France to be put on the front-of-pack of food products. At the individual level, a dietary index (FSA-NPS DI) has been derived and validated and corresponds to a weighted mean of all FSA-NPS scores of foods usually consumed by the individual, reflecting the nutritional quality of his/her diet. Our aim was to investigate the association between the FSA-NPS DI and cancer risk in a large cohort. This prospective study included 6435 participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (1994–2007) who completed at least six 24 h dietary records during the first 2 years of follow-up. FSA-NPS DI was computed for each subject (higher values representing lower nutritional quality of the diet). After a median follow-up of 12·6 years, 453 incident cancers were diagnosed. Associations were characterised by multivariate Cox proportional hazards models. The FSA-NPS DI was directly associated with overall cancer risk (hazard ratio (HR)for a 1-point increment=1·08 (95 % CI 1·01, 1·15), Ptrend=0·02; HRQ5 v. Q1=1·34 (95 % CI 1·00, 1·81), Ptrend=0·03). This association tended to be more specifically observed in subjects with moderate energy intake (≤median, HRfor a 1-point increment=1·10 (95 % CI 1·01-1·20), Ptrend=0·03). No association was observed in subjects with higher energy intake (Ptrend=0·3). Results were not statistically significant for breast and prostate cancer risks. For the first time, this study investigated the prospective association between the FSA-NPS individual score and cancer risk. The results suggest that unhealthy food choices may be associated with a 34 % increase in overall cancer risk, supporting the public health relevance of developing front-of-pack nutrition labels based on this score.
Next generation sequencing for newborn screening: are we there yet?
Authors: FRIEDMAN EITAN
Published: September 2015

Screening programs for asymptomatic newborns (newborn screening – NBS) have increasingly been implemented in many westernized countries since the end of the 20th century (Wilson et al., 2010). The major goal of these programs is to unselectively screen all newborns for a well defined group of severe, rare, clearly identifiable and actionable conditions. These conditions should be diagnosed and treated in a timely fashion to ensure short and long term health of the newborn as an infant and an adult. As such, NBS programs are one of the pivotal public health achievements of the past decade (Centers for Disease Control and Prevention, 2011) that have led to the saving of lives and improving quality of life as well as posing less financial burden on the health care system. Technically the currently practiced screening process is performed 48 hours after birth, using a minute amount of blood collected on a dried blood spot card, which is subsequently subjected to biochemical analysis predominantly using mass spectrometry assays.
Incidence of severe diarrhoea due toVibrio choleraein the catchment area of six surveillance hospitals in Bangladesh
Authors: PAUL R. C. , FARUQUE A. S. G. , ALAM M. , IQBAL A. , ZAMAN K. , ISLAM N. , SOBHAN A. , DAS S. K. , MALEK M. A. , QADRI F. , CRAVIOTO A. , LUBY S.P.
Published: September 2015

Cholera is an important public health problem in Bangladesh. Interventions to prevent cholera depend on their cost-effectiveness which in turn depends on cholera incidence. Hospital-based diarrhoeal disease surveillance has been ongoing in six Bangladeshi hospitals where a systematic proportion of patients admitted with diarrhoea were enrolled and tested forVibrio cholerae.However, incidence calculation using only hospital data underestimates the real disease burden because many ill persons seek treatment elsewhere. We conducted a healthcare utilization survey in the catchment areas of surveillance hospitals to estimate the proportion of severe diarrhoeal cases that were admitted to surveillance hospitals and estimated the population-based incidence of severe diarrhoea due toV. choleraeby combining both hospital surveillance and catchment area survey data. The estimated incidence of severe diarrhoea due to cholera ranged from 0·3 to 4·9/1000 population in the catchment area of surveillance hospitals. In children aged <5 years, incidence ranged from 1·0 to 11·0/1000 children. Diarrhoeal deaths were most common in the Chhatak Hospital's catchment area (18·5/100 000 population). This study provides a credible estimate of the incidence of severe diarrhoea due to cholera in Bangladesh, which can be used to assess the cost-effectiveness of cholera prevention activities.
Energy restriction and potential energy restriction mimetics
Authors: Nikolai Sibylle , Pallauf Kathrin , Huebbe Patricia , Rimbach Gerald
Published: September 2015

Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy-d-glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.
Pour (ne) pas que:une locution conjonctive entre norme(s) et usages
Authors: ADLER SILVIA
Published: September 2015

Cette étude se propose dans un premier temps de faire un tour d'horizon de la question du statut indécis de la tournure finale négativepour (ne) pas queet de celle relative à sa motivation. Chemin faisant, seront exposés des observables qui montreront à quel point cette tournure est productive. Dans un deuxième temps, on évaluera les avantages de la motivation du déplacement du (des) marqueur(s) de négation (ne+pasoupastout seul) à l'extérieur du complexe verbal à la lumière du principe de l'iconicité, piste qui reste moins exploitée dans le traitement depour (ne) pas que.
Contributing to Healing the World
Authors: Dénes Iván Zoltán
Published: September 2015

This paper investigates the resistance, and life-saving activities during the Shoah, of the greatest Hungarian democratic political thinker of the 20th century, István Bibó – one of the most original political theorists of his time. It places this in the context of his intellectual development, and provides an overview of his later thought on Anti-Semitism and the various forms of Jewish identity.
Assessing the Potential Effects of the European Union Multilevel Approach to the Coexistence Policy
Authors: Rodríguez-Entrena Macario , Salazar-Ordóñez Melania
Published: September 2015

European Union (EU) coexistence policy is based on the principle of subsidiarity, which implies a multilevel governance framework. Different legislative approaches have been developed in EU Member States. These legal rules are oriented to both preventing on-farm adventitious admixture (ex-ante regulations) and reducing potential economic consequences (ex-post liability). So coexistence deals with a subject of negative externalities involving an issue of property-right allocation between farmers. Considering the impacts that coexistence policy has on GM (genetically modified) crop adoption rates and the generation of trade distortions, potential effects of the EU coexistence framework are reviewed from a theoretical property-right allocation view. Derived from the analysis, property-right allocation is focused on non-GM farmers according to EU regulation enforcement, which tends to rigid coexistence measures. Nonetheless, the multilevel EU framework has led Member States to pursue their aims: trade interests and social legitimation.
TRANSITION TO TURBULENCE FROM PLANE COUETTE FLOW
Authors: FORBES L. K.
Published: September 2015

Modelling fluid turbulence is perhaps one of the hardest problems in Applied Mathematics. In a recent paper, the author argued that the classical Navier–Stokes equation is not sufficient to describe the transition to turbulence, but that a Reiner–Rivlin type equation is needed instead. This is explored here for the simplest of all viscous fluid flows, the Couette flow, which is a simple shear between two moving plates. It is found that at high wavenumbers, the transition to unstable flow at the critical Reynolds number is characterized by a large number of eigenvalues of the Orr–Sommerfeld equation moving into the unstable zone essentially simultaneously. This would generate high-dimensional chaos almost immediately, and is a suggested mechanism for the transition to turbulence. Stability zones are illustrated for the flow, and a simple asymptotic solution confirms some of the features of these numerical results.
Association of Attention deficit hyperactivity disorder and Kawasaki disease: a nationwide population-based cohort study
Authors: Kuo H.-C. , Chang W.-C. , Wang L.-J. , Li S.-C. , Chang W.-P.
Published: September 2015

Aims.

The association between Kawasaki disease (KD) and Attention deficit hyperactivity disorder (ADHD) has rarely been studied. In this study, we investigated the hypothesis that KD may increase the risk of ADHD using a nationwide Taiwanese population-based claims database.

Methods.

Our study cohort consisted of patients who were diagnosed with KD between January 1997 and December 2005 (N = 651). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 3255). The cumulative incidence of ADHD was 3.89/1000 (from 0.05 to 0.85) in this study. All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed ADHD. Cox proportional hazard regression analysis was performed to evaluate 5-year ADHD-free survival rates.

Results.

Of all patients, 83 (2.1%) developed ADHD during the 5-year follow-up period, of whom 21 (3.2%) had KD and 62 (1.9%) were in the comparison cohort. The patients with KD seemed to be at an increased risk of developing ADHD (crude hazard ratio (HR): 1.71; 95% confidence interval (CI) = 1.04–2.80; p < 0.05). However, after adjusting for gender, age, asthma, allergic rhinitis, atopic dermatitis and meningitis, the adjusted hazard ratios (AHR) of the ADHD in patients with KD showed no association with the controls (AHR: 1.59; 95% CI = 0.96–2.62; p = 0.07). We also investigated whether or not KD was a gender-dependent risk factor for ADHD, and found that male patients with KD did not have an increased risk of ADHD (AHR: 1.62; 95% CI = 0.96–2.74; p = 0.07) compared with the female patients.

Conclusions.

The findings of this population-based study suggest that patients with KD may not have an increased risk of ADHD and whether or not there is an association between KD and ADHD remains uncertain.
EZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway
Authors: Murai Fumihiko , Koinuma Daizo , Shinozaki-Ushiku Aya , Fukayama Masashi , Miyaozono Kohei , Ehata Shogo
Published: September 2015

Transforming growth factor-β (TGF-β) induces apoptosis in many types of cancer cells and acts as a tumor suppressor. We performed a functional analysis of TGF-β signaling to identify a molecular mechanism that regulated survival in small cell lung cancer cells. Here, we found low expression of TGF-β type II receptor (TβRII) in most small cell lung cancer cells and tissues compared to normal lung epithelial cells and normal lung tissues, respectively. When wild-type TβRII was overexpressed in small cell lung cancer cells, TGF-β suppressed cell growth in vitro and tumor formation in vivo through induction of apoptosis. Components of polycomb repressive complex 2, including enhancer of zeste 2 (EZH2), were highly expressed in small cell lung cancer cells; this led to epigenetic silencing of TβRII expression and suppression of TGF-β-mediated apoptosis. Achaete-scute family bHLH transcription factor 1 (ASCL1; also known as ASH1), a Smad-dependent target of TGF-β, was found to induce survival in small cell lung cancer cells. Thus, EZH2 promoted small cell lung cancer progression by suppressing the TGF-β-Smad-ASCL1 pathway.
Common alleles contribute to schizophrenia in CNV carriers
Authors: Tansey K E , Rees E , Linden D E , Ripke S , Chambert K D , Moran J L , McCarroll S A , Holmans P , Kirov G , Walters J , Owen M J , O'Donovan M C
Published: September 2015

The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10−17) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely.
Non-random patterns in viral diversity
Authors: Anthony Simon J. , Islam Ariful , Johnson Christine , Navarrete-Macias Isamara , Liang Eliza , Jain Komal , Hitchens Peta L. , Che Xiaoyu , Soloyvov Alexander , Hicks Allison L. , Ojeda-Flores Rafael , Zambrana-Torrelio Carlos , Ulrich Werner , Rostal Melinda K. , Petrosov Alexandra , Garcia Joel , Haider Najmul , Wolfe Nathan , Goldstein Tracey , Morse Stephen S. , Rahman Mahmudur , Epstein Jonathan H. , Mazet Jonna K. , Daszak Peter , Lipkin W. Ian
Published: September 2015

It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stochastic (not predictable) processes. We sample macaque faeces across nine sites in Bangladesh and use consensus PCR and sequencing to discover 184 viruses from 14 viral families. We then use network modelling and statistical null-hypothesis testing to show the presence of non-random deterministic patterns at different scales, between sites and within individuals. We show that the effects of determinism are not absolute however, as stochastic patterns are also observed. In showing that determinism is an important process in viral community assembly we conclude that it should be possible to forecast changes to some portion of a viral community, however there will always be some portion for which prediction will be unlikely.
An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands
Authors: Jiang Jiefeng , Beck Jeffrey , Heller Katherine , Egner Tobias
Published: September 2015

The anterior cingulate and lateral prefrontal cortices have been implicated in implementing context-appropriate attentional control, but the learning mechanisms underlying our ability to flexibly adapt the control settings to changing environments remain poorly understood. Here we show that human adjustments to varying control demands are captured by a reinforcement learner with a flexible, volatility-driven learning rate. Using model-based functional magnetic resonance imaging, we demonstrate that volatility of control demand is estimated by the anterior insula, which in turn optimizes the prediction of forthcoming demand in the caudate nucleus. The caudate’s prediction of control demand subsequently guides the implementation of proactive and reactive attentional control in dorsal anterior cingulate and dorsolateral prefrontal cortices. These data enhance our understanding of the neuro-computational mechanisms of adaptive behaviour by connecting the classic cingulate-prefrontal cognitive control network to a subcortical control-learning mechanism that infers future demands by flexibly integrating remote and recent past experiences.
An insight into non-emissive excited states in conjugated polymers
Authors: Hu Zhongjian , Willard Adam P. , Ono Robert J. , Bielawski Christopher W. , Rossky Peter J. , Vanden Bout David A.
Published: September 2015

Conjugated polymers in the solid state usually exhibit low fluorescence quantum yields, which limit their applications in many areas such as light-emitting diodes. Despite considerable research efforts, the underlying mechanism still remains controversial and elusive. Here, the nature and properties of excited states in the archetypal polythiophene are investigated via aggregates suspended in solvents with different dielectric constants (ɛ). In relatively polar solvents (ɛ>∼ 3), the aggregates exhibit a low fluorescence quantum yield (QY) of 2–5%, similar to bulk films, however, in relatively nonpolar solvents (ɛ<∼ 3) they demonstrate much higher fluorescence QY up to 20–30%. A series of mixed quantum-classical atomistic simulations illustrate that dielectric induced stabilization of nonradiative charge-transfer (CT) type states can lead to similar drastic reduction in fluorescence QY as seen experimentally. Fluorescence lifetime measurement reveals that the CT-type states exist as a competitive channel of the formation of emissive exciton-type states.
Experimental observation of N00N state Bloch oscillations
Authors: Lebugle Maxime , Gräfe Markus , Heilmann René , Perez-Leija Armando , Nolte Stefan , Szameit Alexander
Published: September 2015

Bloch oscillations of quantum particles manifest themselves as periodic spreading and relocalization of the associated wave functions when traversing lattice potentials subject to external gradient forces. Albeit this phenomenon is deeply rooted into the very foundations of quantum mechanics, all experimental observations so far have only contemplated dynamics of one and two particles initially prepared in separable local states. Evidently, a more general description of genuinely quantum Bloch oscillations will be achieved on excitation of a Bloch oscillator by nonlocal states. Here we report the observation of Bloch oscillations of two-particle N00N states, and discuss the nonlocality on the ground of Bell-like inequalities. The time evolution of two-photon N00N states in Bloch oscillators, whether symmetric, antisymmetric or partially symmetric, reveals transitions from particle antibunching to bunching. Consequently, the initial states can be tailored to produce spatial correlations akin to those of bosons, fermions and anyons, presenting potential applications in photonic quantum simulation.
Atomic description of the immune complex involved in heparin-induced thrombocytopenia
Authors: Cai Zheng , Yarovoi Serge V. , Zhu Zhiqiang , Rauova Lubica , Hayes Vincent , Lebedeva Tatiana , Liu Qun , Poncz Mortimer , Arepally Gowthami , Cines Douglas B. , Greene Mark I.
Published: September 2015

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. The atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.
Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores
Authors: Sanders Jon G. , Beichman Annabel C. , Roman Joe , Scott Jarrod J. , Emerson David , McCarthy James J. , Girguis Peter R.
Published: September 2015

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.
Strong interface-induced spin–orbit interaction in graphene on WS2
Authors: Wang Zhe , Ki Dong–Keun , Chen Hua , Berger Helmuth , MacDonald Allan H. , Morpurgo Alberto F.
Published: September 2015

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in graphene on hexagonal boron nitride substrates. Ongoing research strives to explore interfacial interactions with other materials to engineer targeted electronic properties. Here we show that with a tungsten disulfide (WS2) substrate, the strength of the spin–orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization effect and to a spin-relaxation time two to three orders of magnitude smaller than in graphene on conventional substrates. To interpret our findings we have performed first-principle electronic structure calculations, which confirm that carriers in graphene on WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.
Structural permeability of complex networks to control signals
Authors: Lo Iudice Francesco , Garofalo Franco , Sorrentino Francesco
Published: September 2015

Many biological, social and technological systems can be described as complex networks. The goal of affecting their behaviour has motivated recent work focusing on the relationship between the network structure and its propensity to be controlled. While this work has provided insight into several relevant problems, a comprehensive approach to address partial and complete controllability of networks is still lacking. Here, we bridge this gap by developing a framework to maximize the diffusion of the control signals through a network, while taking into account physical and economic constraints that inevitably arise in applications. This approach allows us to introduce the network permeability, a unified metric of the propensity of a network to be controllable. The analysis of the permeability of several synthetic and real networks enables us to extract some structural features that deepen our quantitative understanding of the ease with which specific controllability requirements can be met.
Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls
Authors: Zhu Zezhang , Tang Nelson Leung-Sang , Xu Leilei , Qin Xiaodong , Mao Saihu , Song Yueming , Liu Limin , Li Fangcai , Liu Peng , Yi Long , Chang Jiang , Jiang Long , Ng Bobby Kin-Wah , Shi Benlong , Zhang Wen , Qiao Jun , Sun Xu , Qiu Xusheng , Wang Zhou , Wang Fei , Xie Dingding , Chen Ling , Chen Zhonghui , Jin Mengran , Han Xiao , Hu Zongshan , Zhang Zhen , Liu Zhen , Zhu Feng , Qian Bang-ping , Yu Yang , Wang Bing , Lee K. M. , Lee Wayne Y.W. , Lam T. P. , Qiu Yong , Cheng Jack Chun-Yiu
Published: September 2015

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.
Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum
Authors: Kim Sangwoo , Jang Yu-Sin , Ha Sung-Chul , Ahn Jae-Woo , Kim Eun-Jung , Hong Lim Jae , Cho Changhee , Shin Ryu Yong , Kuk Lee Sung , Lee Sang Yup , Kim Kyung-Jin
Published: September 2015

Thiolase is the first enzyme catalysing the condensation of two acetyl-coenzyme A (CoA) molecules to form acetoacetyl-CoA in a dedicated pathway towards the biosynthesis of n-butanol, an important solvent and biofuel. Here we elucidate the crystal structure of Clostridium acetobutylicum thiolase (CaTHL) in its reduced/oxidized states. CaTHL, unlike those from other aerobic bacteria such as Escherichia coli and Zoogloea ramegera, is regulated by the redox-switch modulation through reversible disulfide bond formation between two catalytic cysteine residues, Cys88 and Cys378. When CaTHL is overexpressed in wild-type C. acetobutylicum, butanol production is reduced due to the disturbance of acidogenic to solventogenic shift. The CaTHLV77Q/N153Y/A286K mutant, which is not able to form disulfide bonds, exhibits higher activity than wild-type CaTHL, and enhances butanol production upon overexpression. On the basis of these results, we suggest that CaTHL functions as a key enzyme in the regulation of the main metabolism of C. acetobutylicum through a redox-switch regulatory mechanism.
Highly efficient and ultra-broadband graphene oxide ultrathin lenses with three-dimensional subwavelength focusing
Authors: Zheng Xiaorui , Jia Baohua , Lin Han , Qiu Ling , Li Dan , Gu Min
Published: September 2015

Nanometric flat lenses with three-dimensional subwavelength focusing are indispensable in miniaturized optical systems. However, they are fundamentally challenging to achieve because of the difficulties in accurately controlling the optical wavefront by a film with nanometric thickness. Based on the unique and giant refractive index and absorption modulations of the sprayable graphene oxide thin film during its laser reduction process, we demonstrate a graphene oxide ultrathin (∼200 nm) flat lens that shows far-field three-dimensional subwavelength focusing (λ3/5) with an absolute focusing efficiency of >32% for a broad wavelength range from 400 to 1,500 nm. Our flexible graphene oxide lenses are mechanically robust and maintain excellent focusing properties under high stress. The simple and scalable fabrication approach enables wide potential applications in on-chip nanophotonics. The wavefront shaping concept opens up new avenues for easily accessible, highly precise and efficient optical beam manipulations with a flexible and integratable planar graphene oxide ultrathin film.
Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes
Authors: Groen Bart , van der Wijk Anne-Eva , van den Berg Paul P. , Lefrandt Joop D. , Gerrit van den Berg  , Sollie Krystina M. , de Vos Paul , Links Thera P. , Faas Marijke M.
Published: September 2015

Despite adequate glycemic control, pregnancy outcome of women with type 1 diabetes (T1D) is still unfavorable as compared to healthy women. In a rat-model of T1D under normoglycemic conditions, adverse pregnancy outcome was also observed, which was associated with aberrant immunological adaptations to pregnancy. Because similar processes may occur in women with T1D we studied the systemic immune response in non-pregnant and pregnant women with and without T1D. The systemic immune response was assessed by using flow cytometry to evaluate the number and activational status of subpopulations of lymphocytes, Natural Killer cells and monocytes in peripheral blood of non-pregnant and pregnant women with and without T1D. An increased white blood cell count, an increased Th1/Th2 ratio, increased Natural Killer cell expression of CD335 and enhanced activation of intermediate and non-classical monocytes was observed in pregnant women with T1D vs. healthy pregnant women. Also, the pregnancy outcome (i.e. incidence of preterm delivery and macrosomia) of women with T1D was unfavorable as compared to healthy women. This study showed that in T1D, the immunological adaptations to pregnancy are disturbed. In addition to hyperglycemia, these different immunological adaptations may be responsible for the greater frequency of complications in pregnant women with T1D.
Correction: Corrigendum: Hidden non-Fermi liquid behavior caused by magnetic phase transition in Ni-doped Ba-122 pnictides
Authors: Lee Seokbae , Choi Ki-Young , Jung Eilho , Roh Seulki , Shin Soohyeon , Park Tuson , Hwang Jungseek
Published: September 2015

We studied two BaFe2−xNixAs2 (Ni-doped Ba-122) single crystals at two different doping levels (underdoped and optimally doped) using an optical spectroscopic technique. The underdoped sample shows a magnetic phase transition around 80 K. We analyze the data with a Drude-Lorentz model with two Drude components (D1 and D2). It is known that the narrow D1 component originates from electron carriers in the electron-pockets and the broad D2 mode is from hole carriers in the hole-pockets. While the plasma frequencies of both Drude components and the static scattering rate of the broad D2 component show negligible temperature dependencies, the static scattering rate of the D1 mode shows strong temperature dependence for the both samples. We observed a hidden quasi-linear temperature dependence in the scattering rate of the D1 mode above and below the magnetic transition temperature while in the optimally doped sample the scattering rate shows a more quadratic temperature dependence. The hidden non-Fermi liquid behavior in the underdoped sample seems to be related to the magnetic phase of the material.
Self make-up: the influence of self-referential processing on attention orienting
Authors: Zhao Shuo , Uono Shota , Yoshimura Sayaka , Toichi Motomi
Published: September 2015

For humans, both eye gaze and arrows serve as powerful signals for orienting attention. Recent studies have shown important differences between gaze and arrows in attention orienting; however, the mechanisms underlying these differences are not known. One such mechanism may be self-referential processing. To investigate this possibility, we trained participants to associate two cues (a red and green arrow in Experiment 1A and two different faces in Experiment 1B) with distinct words (“self” and “other”). Then, we manipulated two types of sound (voice and tone) as targets to investigate whether the cueing effect to self- and other-referential cues differs in a manner similar to that reported for gaze and arrows. We found that self-, but not other-, referential cues induced an enhanced cueing effect to the voice target relative to the tone target regardless of the cue characteristic (i.e., biological or non-biological). Our results suggest that the difference between gaze and arrows in orienting attention can be explained, at least in part, by the self-referentiality of gaze. Furthermore, in Experiment 2, we found a reverse cueing pattern between gaze and arrow cues by manipulating subjects’ experiences, suggesting that differences in the self-referentiality of gaze and arrow cues are not inherent.
Combining Small-Vertebrate, Marine and Stable-Isotope Data to Reconstruct Past Environments
Authors: Rofes Juan , Garcia-Ibaibarriaga Naroa , Aguirre Mikel , Martínez-García Blanca , Ortega Luis , Zuluaga María Cruz , Bailon Salvador , Alonso-Olazabal Ainhoa , Castaños Jone , Murelaga Xabier
Published: September 2015

Three very different records are combined here to reconstruct the evolution of environments in the Cantabrian Region during the Upper Pleistocene, covering ~35.000 years. Two of these records come from Antoliñako Koba (Bizkaia, Spain), an exceptional prehistoric deposit comprising 9 chrono-cultural units (Aurignacian to Epipaleolithic). The palaeoecological signal of small-vertebrate communities and red deer stable-isotope data (δ13C and δ15N) from this mainland site are contrasted to marine microfaunal evidence (planktonic and benthic foraminifers, ostracods and δ18O data) gathered at the southern Bay of Biscay. Many radiocarbon dates for the Antoliña’s sequence, made it possible to compare the different proxies among them and with other well-known North-Atlantic records. Cooling and warming events regionally recorded, mostly coincide with the climatic evolution of the Upper Pleistocene in the north hemisphere.
Post-conflict affiliation as conflict management in captive bottlenose dolphins (Tursiops truncatus)
Authors: Yamamoto Chisato , Morisaka Tadamichi , Furuta Keisuke , Ishibashi Toshiaki , Yoshida Akihiko , Taki Michihiro , Mori Yoshihisa , Amano Masao
Published: September 2015

Post-conflict affiliation between former opponents or between one of the former opponents and bystanders might have the function of conflict management, which reduces the costs associated with aggressions. One of the suggested functions of post-conflict affiliation is decreased renewed aggressions directed from aggressors to victims. However, the effect of post-conflict affiliation on renewed aggressions by victims has not been investigated. We examined whether post-conflict affiliations decreased the number of renewed aggressions initiated by winners or losers in captive bottlenose dolphins. Both winners and losers initiated renewed aggressions. However, these aggressions decreased after post-conflict affiliation between former opponents, initiated by bystanders to winners, initiated by losers to bystanders and initiated by bystanders to losers. Post-conflict affiliation between former opponents is suggested to function as reconciliation. Post–conflict affiliation initiated by losers to bystanders is suggested to function as the protection of losers. Post-conflict affiliations initiated by bystanders to one of former opponents are suggested to function as both appeasement and protection of the opponent who affiliates with bystanders.
Surface-Engineered Graphene Quantum Dots Incorporated into Polymer Layers for High Performance Organic Photovoltaics
Authors: Kim Jung Kyu , Kim Sang Jin , Park Myung Jin , Bae Sukang , Cho Sung-Pyo , Du Qing Guo , Wang Dong Hwan , Park Jong Hyeok , Hong Byung Hee
Published: September 2015

Graphene quantum dots (GQDs), a newly emerging 0-dimensional graphene based material, have been widely exploited in optoelectronic devices due to their tunable optical and electronic properties depending on their functional groups. Moreover, the dispersibility of GQDs in common solvents depending on hydrophobicity or hydrophilicity can be controlled by chemical functionalization, which is particularly important for homogeneous incorporation into various polymer layers. Here we report that a surface-engineered GQD-incorporated polymer photovoltaic device shows enhanced power conversion efficiency (PCE), where the oxygen-related functionalization of GQDs enabled good dispersity in a PEDOT:PSS hole extraction layer, leading to significantly improved short circuit current density (Jsc) value. To maximize the PCE of the device, hydrophobic GQDs that are hydrothermally reduced (rGQD) were additionally incorporated in a bulk-heterojunction layer, which is found to promote a synergistic effect with the GQD-incorporated hole extraction layer.
T cell immunity to glatiramer acetate ameliorates cognitive deficits induced by chronic cerebral hypoperfusion by modulating the microenvironment
Authors: Chen Li , Yao Yang , Wei Changjuan , Sun Yanan , Ma Xiaofeng , Zhang Rongxin , Xu Xiaolin , Hao Junwei
Published: September 2015

Vascular dementia (VaD) is a progressive and highly prevalent disorder. However, in a very large majority of cases, a milieu of cellular and molecular events common for multiple neurodegenerative diseases is involved. Our work focused on whether the immunomodulating effect of glatiramer acetate (GA) could restore normalcy to the microenvironment and ameliorate cognitive decline induced by chronic cerebral hypoperfusion. We assessed cognitive function by rats’ performance in a Morris water maze (MWM), electrophysiological recordings and by pathologic changes. The results suggest that GA reduced cognitive deficits by reestablishing an optimal microenvironment such as increasing expression of the brain-derived neurotrophic factor (BDNF) and modulating the Th1/Th2 cytokine balance in the hippocampus. When microenvironmental homeostasis is restored, cholinergic activity becomes involved in ameliorating cellular damage. Since vaccination with GA can boost “protective autoimmunity” in this way, a similar strategy may have therapeutic potential for alleviating VaD disease.
A novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo
Authors: Figueiredo Carlos R. , Matsuo Alisson L. , Azevedo Ricardo A. , Massaoka Mariana H. , Girola Natalia , Polonelli Luciano , Travassos Luiz R.
Published: September 2015

Short peptide sequences from complementarity-determining regions (CDRs) of different immunoglobulins may exert anti-infective, immunomodulatory and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). In this sense, they resemble early molecules of innate immunity. C36L1 was identified as a bioactive light-chain CDR1 peptide by screening 19 conserved CDR sequences targeting murine B16F10-Nex2 melanoma. The 17-amino acid peptide is readily taken up by melanoma cells and acts on microtubules causing depolymerization, stress of the endoplasmic reticulum and intrinsic apoptosis. At low concentrations, C36L1 inhibited migration, invasion and proliferation of B16F10-Nex2 cells with cell cycle arrest at G2/M phase, by regulating the PI3K/Akt signaling axis involving Rho-GTPase and PTEN mediation. Peritumor injection of the peptide delayed growth of subcutaneously grafted melanoma cells. Intraperitoneal administration of C36L1 induced a significant immune-response dependent anti-tumor protection in a syngeneic metastatic melanoma model. Dendritic cells stimulated ex-vivo by the peptide and transferred to animals challenged with tumor cells were equally effective. The C36 VL CDR1 peptide is a promising microtubule-interacting drug that induces tumor cell death by apoptosis and inhibits metastases of highly aggressive melanoma cells.
Visualization of expanding warm dense gold and diamond heated rapidly by laser-generated ion beams
Authors: Bang W. , Albright B. J. , Bradley P. A. , Gautier D. C. , Palaniyappan S. , Vold E. L. , Cordoba M. A. Santiago , Hamilton C. E. , Fernández J. C.
Published: September 2015

With the development of several novel heating sources, scientists can now heat a small sample isochorically above 10,000 K. Although matter at such an extreme state, known as warm dense matter, is commonly found in astrophysics (e.g., in planetary cores) as well as in high energy density physics experiments, its properties are not well understood and are difficult to predict theoretically. This is because the approximations made to describe condensed matter or high-temperature plasmas are invalid in this intermediate regime. A sufficiently large warm dense matter sample that is uniformly heated would be ideal for these studies, but has been unavailable to date. Here we have used a beam of quasi-monoenergetic aluminum ions to heat gold and diamond foils uniformly and isochorically. For the first time, we visualized directly the expanding warm dense gold and diamond with an optical streak camera. Furthermore, we present a new technique to determine the initial temperature of these heated samples from the measured expansion speeds of gold and diamond into vacuum. We anticipate the uniformly heated solid density target will allow for direct quantitative measurements of equation-of-state, conductivity, opacity and stopping power of warm dense matter, benefiting plasma physics, astrophysics and nuclear physics.
Predictive diagnosis of the risk of breast cancer recurrence after surgery by single-particle quantum dot imaging
Authors: Gonda Kohsuke , Miyashita Minoru , Higuchi Hideo , Tada Hiroshi , Watanabe Tomonobu M. , Watanabe Mika , Ishida Takanori , Ohuchi Noriaki
Published: September 2015

In breast cancer, the prognosis of human epidermal growth factor receptor 2 (HER2)-positive patients (20–25%) has been dramatically improved by the clinical application of the anti-HER2 antibody drugs trastuzumab and pertuzumab. However, the clinical outcomes of HER2-negative cases with a poor prognosis have not improved and novel therapeutic antibody drugs or diagnostic molecular markers of prognosis are urgently needed. Here, we targeted protease-activated receptor 1 (PAR1) as a new biomarker for HER2-negative patients. The developed anti-PAR1 antibody inhibited PAR1 activation by matrix metalloprotease 1 and thereby prevented cancer-cell migration and invasion. To estimate PAR1 expression levels in HER2-negative patient tissues using the antibody, user-friendly immunohistochemistry with fluorescence nanoparticles or quantum dots (QDs) was developed. Previously, immunohistochemistry with QDs was affected by tissue autofluorescence, making quantitative measurement extremely difficult. We significantly improved the quantitative sensitivity of immunohistochemistry with QDs by using an autofluorescence-subtracted image and single-QD imaging. The immunohistochemistry showed that PAR1 expression was strongly correlated with relapse-free survival time in HER2-negative breast cancer patients. Therefore, the developed anti-PAR1 antibody is a strong candidate for use as an anticancer drug and a prognostic biomarker for HER2-negative patients.
Shared functional defect in IP3R-mediated calcium signaling in diverse monogenic autism syndromes
Authors: Schmunk G , Boubion B J , Smith I F , Parker I , Gargus J J
Published: September 2015

Autism spectrum disorder (ASD) affects 2% of children, and is characterized by impaired social and communication skills together with repetitive, stereotypic behavior. The pathophysiology of ASD is complex due to genetic and environmental heterogeneity, complicating the development of therapies and making diagnosis challenging. Growing genetic evidence supports a role of disrupted Ca2+ signaling in ASD. Here, we report that patient-derived fibroblasts from three monogenic models of ASD—fragile X and tuberous sclerosis TSC1 and TSC2 syndromes—display depressed Ca2+ release through inositol trisphosphate receptors (IP3Rs). This was apparent in Ca2+ signals evoked by G protein-coupled receptors and by photoreleased IP3 at the levels of both global and local elementary Ca2+ events, suggesting fundamental defects in IP3R channel activity in ASD. Given the ubiquitous involvement of IP3R-mediated Ca2+ signaling in neuronal excitability, synaptic plasticity, gene expression and neurodevelopment, we propose dysregulated IP3R signaling as a nexus where genes altered in ASD converge to exert their deleterious effect. These findings highlight potential pharmaceutical targets, and identify Ca2+ screening in skin fibroblasts as a promising technique for early detection of individuals susceptible to ASD.
Synthesis and characterization of a magnetic molecularly imprinted polymer for the selective extraction of nicotine and cotinine from urine samples followed by GC-MS analysis
Authors: Franqui Lidiane Silva , Santos Mariane Gonçalves , Virtuoso Luciano Sindra , Maia Patrícia Penido , Figueiredo Eduardo Costa
Published: September 2015

A magnetic molecularly imprinted polymer (MMIP) was synthesized, characterized and used in the selective extraction of nicotine and cotinine from urine samples.
Single-cell migration as studied by scanning electrochemical microscopy
Authors: Ummadi J. Ganesh , Joshi Vrushali S. , Gupta Priya R. , Indra Arup K. , Koley Dipankar
Published: September 2015

An SECM based analytical method to study single-cell biomechanics is reported to differentiate between migrating and stationary cancer cells.
Bioimaging of microRNA34c in a single sperm using a molecular beacon
Authors: Ko Hae Young , Lee Jonghwan , Moon Sung Ung , Lee Yong Seung , Cho Sujeong , Kim Soonhag
Published: September 2015

The VisuFect-conjugated molecular beacon was developed for non-invasive visualization of microRNA34c in a living single mouse sperm.
From self-sorted coordination libraries to networking nanoswitches for catalysis
Authors: Schmittel Michael
Published: September 2015

This feature article sketches our long way from the development of dynamic heteroleptic coordination motifs to the self-sorting of multi-component libraries and finally the design of a new family of triangular nanomechanical switches, which are useful for ON–OFF control of catalysis and in bidirectional communication.
Water-assisted self-photoredox of 2-(1-hydroxyethyl)-9,10-anthraquinone through a triplet excited state intra-molecular proton transfer pathway
Authors: Dai Jingze , Han Juan , Chen Xuebo , Fang Weihai , Ma Jiani , Phillips David Lee
Published: September 2015

A novel self-photoredox reaction for 2-(1-hydroxyethyl)-9,10-anthraquinone has been theoretically rationalized to take place through two steps of triplet excited state intra-molecular proton transfer aided by water wires.