bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative analysis of the restaurant consumer food environment in Rochester (NY, USA) and London (ON, Canada): assessing children’s menus by neighbourhood socio-economic characteristics
Authors: DuBreck Catherine M , Sadler Richard C , Arku Godwin , Seabrook Jamie , Gilliland Jason
Published: February 2019

Objective

To assess restaurant children’s menus for content and nutritional quality; and to investigate the relationship between the restaurant consumer food environment for children and neighbourhood-level socio-economic characteristics within and between one Canadian city and one US city.

Design

Cross-sectional observational study.

Setting

London, ON, Canada and Rochester, NY, USA.

Participants

Restaurant children’s menus were assessed, scored and compared using the Children’s Menu Assessment tool. We quantified neighbourhood accessibility to restaurants by calculating 800 m road-network buffers around the centroid of each city census block and created a new Neighbourhood Restaurant Quality Index for Children (NRQI-C) comprising the sum of restaurant menu scores divided by the total number of restaurants within each area. After weighting by population, we examined associations between NRQI-C and neighbourhood socio-economic characteristics using correlations and multiple regression analyses.

Results

Nutritional quality of children’s menus was greater, on average, in Rochester compared with London. Only one variable remained significant in the regression analyses for both cities: proportion of visible minorities had a positive effect on neighbourhood NRQI-C scores in London, whereas the reverse was true in Rochester.

Conclusions

Results suggest the presence of a socio-economic disparity within Rochester, where children in more disadvantaged areas have poorer access to better nutritional quality restaurant choices. In London, results suggest an inverse relationship across the city where children in more disadvantaged areas have better access to better nutritional quality restaurant choices. Given these disparate results, research on restaurant nutritional quality for children requires additional consideration.
Development and testing of a scale to evaluate diet according to the recommendations of the Dietary Guidelines for the Brazilian Population
Authors: Gabe Kamila Tiemann , Jaime Patricia Constante
Published: February 2019

Objective

To develop and test a scale for healthy eating practices measurement according to the Dietary Guidelines for the Brazilian Population recommendations.

Design

Methodological study. The current Brazilian food-based dietary guideline highlights the importance of choosing foods, combining foods to create meals and modes of eating. These recommendations formed the main domains of the scale and served as a basis for the development of ninety-six items, each with a 4-point Likert response option. Content and face validity were tested. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to determine construct validity. Internal consistency was determined using α and ω coefficients, and reproducibility was tested using test–retest.

Setting

Brazil.

Participants

A ten-member expert panel was used to assess content validity. Adults aged 18–60 years were included in the face validity (n 20), EFA (n 352), CFA and reliability tests (n 900).

Results

Of the ninety-six initial items, twenty-four were excluded and fifty-five were reworded following the content and face validations. EFA detected a four-domain structure (Food choices, Modes of eating, Planning and Domestic organization), which explained 41 % of the variance. CFA led to a final twenty-four-item model with acceptable goodness-of-fit indices and good reliability measures (α=0·77; ω=0·83). Intraclass correlation coefficient for the total score (0·82) and analysis of the Bland–Altman plot suggested good reproducibility of the scale.

Conclusions

The scale presents good evidence of validity and reliability. This innovative study created a useful tool for evaluation of the impact of the Dietary Guidelines for the Brazilian Population.
Russian “Federalism”: Illiberal? Imperial? Exceptionalist?
Authors: Makarychev Andrey , Yatsyk Alexandra
Published: February 2019

Relations between the center and regions in Russia, being always in the limelight of attention in political science literature, remain a battlefield of different scholarly interpretations. Several narratives shape the current debate on Russian subnational regionalism or, in very legalistic terms, “federalism.” One is bent on applying to Russia such normatively-loaded concepts as multilevel and networked governance, meta-governance, indigenous governance, civil society participation, and others with strong liberal and institutional pedigrees. In this vein, Russia might be referred to—for example, along with Germany and France—as a “post-imperial democracy,” with an implicit anticipation of the prefix “post-” to signify Moscow's commitment to a democratic, rather than imperial, future. Seen from this perspective, with all its specificity Russia still conforms to basic standards of democratic rule and therefore can be approached, described, and analyzed in the language applicable to the liberal west, where institutions mitigate controversies over interests and create consensus over rules of the game.
Affirmative Action in the Western Borderlands of the Late Russian Empire?
Authors: Staliūnas Darius
Published: February 2019

This article argues that apart from a couple of cases, there were no situations where the Russian imperial government would have supported Lithuanian national culture as a counterbalance against Poles, and more generally, that the policy of “divide and rule” was in principle not applied on the empire's western periphery regarding other non-dominant ethnic groups. A more general reason for not implementing such a policy was related to many officials’ belief that the government should seek integration, acculturation, or even assimilation of non-Russian ethnicities. At the same time, on the Russian mental map, the Northwest Region was understood not just as part of the empire, but as part of Russian national territory. In such a territory, most of the government subscribed to a discourse of nationalism that permitted no means of support for the strengthening of non-Russian nationalisms. Finally, social radicalism of the Lithuanian, Latvian, or Estonian national movements was another obstacle for tsarist officials to support these “peasant” nationalities.
Physicochemical properties and health benefits of pistachio nuts
Authors: Esmaeili Nadimi Ali , Ahmadi Zahra , Falahati-pour Soudeh Khanamani , Mohamadi Maryam , Nazari Alireza , Hassanshahi Gholamhossein , Ekramzadeh Maryam
Published: February 2019

Abstract. The genus of Pistacia plant systematically fits into the family of Anacardiaceae. Pistachios contain protein, carbohydrate, dietary fibers, fat, folic acid, vitamin K, magnesium and potassium, gama-tocopherols, phytochemicals, and polyphenols. Collectively, these constituents have been shown to possess antioxidant and anti-inflammatory functions to improve overall health when consumed as a healthy diet. We searched the following keywords within the literature databases: pistachio, heart disorders, lipids, weight, antioxidants, and allergy. Further searching theses keywords, we have found 50 articles in PubMed, 40 articles in ISI web of knowledge and 30 articles in Google Scholar. We have selected 100 articles, among them 80 articles were used as the references of this review. In the current article, we have discussed the most recent data published regarding the regulatory effects of pistachios on several clinical states such as heart related disorders, hyperlipidemia, hypertension, vascular stiffness and endothelial and gut functions, weight management, glucose metabolism, kidney function and finally allergies.
In search for an alternative to sugar to reduce obesity
Authors: Mooradian Arshag D.
Published: February 2019

Abstract. Consumption of table sugar has been increasing despite the warnings of public health officials as to the potential adverse consequences of sugar consumption. The World Health Organization recommends restricting consumption of sugars to no more than 10% of daily caloric intake, with a proposal to lower this level to 5% or less for optimal health. Unfortunately substituting sugar with the currently available artificial sweeteners does not appear to have favorable clinical effects. Given the health-related concerns with the currently available sweeteners such as increased risk of obesity and type 2 diabetes there is renewed interest in identifying a safe and palatable sweetener. The sweet extracts of natural plants such as stevia and monk fruit as well as naturally occurring rare sugars have become attractive alternatives. Although most of the sweeteners are sugars, there are some proteins such as braziien and miraculin that have intense sweetness and are being developed as sweeteners. Several companies are pursuing the development of “bitterness-blockers” to remove flavor defects. Other novel approaches include coating mineral carriers with sugar or hollowing out the sugar crystals. Naturally occurring rare sugars such as D-allulose (D-psicose), D-tagatose, D-sorbose and D-allose are attractive sweeteners. They do have the bulk and the mouth fill of table sugar with reduced caloric content (0.2 kcal/g for D-allulose). Additional randomized controlled trials are necessary to define the long term safety and efficacy of these sugars.
Adequate or elevated dietary folate does not ameliorate the reduced antioxidant capacity induced by vitamin B12 deficiency in aged rats
Authors: Úbeda Natalia , Partearroyo Teresa , Varela-Moreiras Gregorio
Published: February 2019

Abstract. Folate could have an antioxidant role but also may be detrimental under vitamin B12 deficiency. The aim was to investigate the effect of different dietary folic acid (FA) levels, on oxidative stress in B12 induced deficient aged rats. Thirty-five male aged Sprague–Dawley rats, were fed either a vitamin B12 deficient (n = 27) or a control diet (n = 8) during eight weeks. Then, animals were divided into four groups: B12 and FA deficient diet (DBDF), B12 deficient diet and FA control diet (DBCF), B12 deficient diet and FA supplemented diet (DBSF), and control diet (CBCF) for a 30 days period. Methionine metabolism and antioxidant status were evaluated. Both vitamins deficiencies elevated serum homocysteine (Hcy) (7.7 vs. 4.3 μmol/L, p < 0.05) and reduced S-adenosylmethionine hepatic content (283.7 vs. 581.9 μg/g protein, p < 0.05), the total antioxidant capacity (155.7 vs. 189.3 μmol/L, p < 0.05), glutathione (GSH) (120.5 vs. 419.9 μg/mg protein, p < 0.05) and oxidized glutathione (0.9 vs. 2.6 μg/mg protein, p < 0.05) compared to control. Activities of glutathione peroxidase and glutathione reductase enzymes or damage to macromolecules were unaffected. Adequate or elevated dietary FA in B12 deficiency rats decreased Hcy (5.7 and 6.3 μmol/L, respectively) and increased total antioxidant capacity (189.8 and 192.6 μmol/L, respectively) to values similar to control group, whereas GSH concentration was significantly lower than control (209.1 and 208.0 μg/mg protein respectively, p < 0.05). In conclusion, in a vitamin B12 deficiency status, adequate or elevated FA prevented impairment in one-carbon metabolism, but does not fully reverse the decrease in antioxidant capacity.
Water on Mars, With a Grain of Salt: Local Heat Anomalies Are Required for Basal Melting of Ice at the South Pole Today
Authors: Sori Michael M. , Bramson Ali M.
Published: February 2019

Recent analysis of radar data from the Mars Express spacecraft has interpreted bright subsurface radar reflections as indicators of local liquid water at the base of the south polar layered deposits (SPLD). However, the physical and geological conditions required to produce melting at this location were not quantified. Here we use thermophysical models to constrain parameters necessary to generate liquid water beneath the SPLD. We show that no concentration of salt is sufficient to melt ice at the base of the SPLD in the present day under typical Martian conditions. Instead, a local enhancement in the geothermal heat flux of >72 mW/m2 is required, even under the most favorable compositional considerations. This heat flow is most simply achieved via the presence of a subsurface magma chamber emplaced 100 s of kyr ago. Thus, if the liquid water interpretation of the observations is correct, magmatism on Mars may have been active extremely recently.
Exchange Processes Induced by Large Horizontal Coherent Structures in Floodplain Vegetated Channels
Authors: Truong S. H. , Uijttewaal W. S. J. , Stive M. J. F.
Published: February 2019

Mangrove forests along the Mekong delta estuaries are usually observed to degrade together with the increasing extension of fish farms. In this limited‐width condition, the formation of coherent structures, their interactions with mangroves, the role of the width of the mangrove forest, and their effects on the exchange processes between the open channel and the adjacent floodplain are still not well examined. In order to obtain more insight, a unique laboratory experiment of a vegetated compound channel mimicking estuarine mangroves has been conducted. The results show that in a compound vegetated channel with a very gentle transverse slope, the vegetated shear layer dynamics resembled that associated with vegetation rather than that associated with a depth differential. Furthermore, the flow field under the effect of large horizontal coherent structures (LHCSs) shows a spatially and temporally cycloid motion with associated flow events, namely, sweep, ejection, stagnant, and reverse flows. It is also suggested that the coherent structures can have an influence on a broader area than the vegetation area into which the eddy structures can penetrate. In terms of the exchange processes, the momentum transfer and the intensity of transverse fluctuations induced by the LHCSs can be related to this phenomenon. Consequently, decreasing the mangrove width can significantly affect the pattern of the LHCSs, disturb the transverse exchange processes induced by these structures, and thereby changing the shear layer, creating unfavorable conditions for sedimentation inside forests and for river bank stability.
Improving Permafrost Modeling by Assimilating Remotely Sensed Soil Moisture
Authors: Zwieback S. , Westermann S. , Langer M. , Boike J. , Marsh P. , Berg A.
Published: February 2019

Knowledge of soil moisture conditions is important for modeling soil temperatures, as soil moisture influences the thermal dynamics in multiple ways. However, in permafrost regions, soil moisture is highly heterogeneous and difficult to model. Satellite soil moisture data may fill this gap, but the degree to which they can improve permafrost modeling is unknown. To explore their added value for modeling soil temperatures, we assimilate fine‐scale satellite surface soil moisture into the CryoGrid‐3 permafrost model, which accounts for the soil moisture's influence on the soil thermal properties and the surface energy balance. At our study site in the Canadian Arctic, the assimilation improves the estimates of deeper (>10 cm) soil temperatures during summer but not consistently those of the near‐surface temperatures. The improvements in the deeper temperatures are strongly contingent on soil type: They are largest for porous organic soils (30%), smaller for thin organic soil covers (20%), and they essentially vanish for mineral soils (only synthetic data available). That the improvements are greatest over organic soils reflects the strong coupling between soil moisture and deeper temperatures. The coupling arises largely from the diminishing soil thermal conductivity with increasing desiccation thanks to which the deeper soil is kept cool. It is this association of dry organic soils being cool at depth that lets the assimilation revise the simulated soil temperatures toward the actually measured ones. In the future, the increasing availability of satellite soil moisture data holds promise for the operational monitoring of soil temperatures, hydrology, and biogeochemistry.
Controls on Near‐Surface Hydraulic Conductivity in a Raised Bog
Authors: Morris Paul J. , Baird Andy J. , Eades Phil A. , Surridge Ben W. J.
Published: February 2019

Shallow water tables protect northern peatlands and their important carbon stocks from aerobic decomposition. Hydraulic conductivity, K, is a key control on water tables. The controls on K, particularly in degraded and restored peatlands, remain a subject of ongoing research. We took 29 shallow (~50 cm) peat cores from an estuarine raised bog in Wales, UK. Parts of the bog are in close‐to‐natural condition, while other areas have undergone shallow peat cutting for fuel and drainage, followed by restoration through ditch blocking. In the laboratory we measured horizontal (Kh) and vertical (Kv) hydraulic conductivity. We fitted linear multiple regression models to describe log10‐transformed Kh and Kv on the basis of simple, easy‐to‐measure predictors. Dry bulk density and degree of decomposition were the strongest predictors of Kh and Kv. Perhaps surprisingly, the independent effect of hummocks was to produce higher‐Kv peat than in lawns; while the independent effect of restored diggings was to produce higher‐K peat than in uncut locations. Our models offer high explanatory power for Kh (adjusted r2 = 0.740) and Kv (adjusted r2 = 0.787). Our findings indicate that generalizable predictive models of peat K, similar to pedotransfer functions for mineral soils, may be attainable. Kh and Kv possess subtly different controls that are consistent with the contrasting roles of these two properties in peatland water budgets. Our near‐surface samples show no evidence for the low‐K marginal peat previously observed in deeper layers at the same site, indicating that such structures may be less important than previously believed.
Immunoglobulin G modulation of the melanocortin 4 receptor signaling in obesity and eating disorders
Authors: Lucas Nicolas , Legrand Romain , Bôle-Feysot Christine , Breton Jonathan , Coëffier Moïse , Akkermann Kirsti , Järv Anu , Harro Jaanus , Déchelotte Pierre , Fetissov Sergueï O.
Published: February 2019

Melanocortin 4 receptor (MC4R) plays a key role in regulation of appetite activated by its main ligand α-melanocyte-stimulating hormone (α-MSH) in both central and peripheral targets. α-MSH also binds to circulating immunoglobulins (Igs) but the functional significance of such immune complexes (ICs) in MC4R signaling in normal and pathological conditions of altered appetite has remained unknown. To address this question, we analyzed plasma levels, affinity kinetics, and binding epitopes of α-MSH-reactive IgG extracted from plasma samples of female patients with hyperphagic obesity, anorexia nervosa, bulimia nervosa, binge-eating disorder, and healthy controls. Ability of α-MSH/IgG IC to bind and activate human MC4R were studied in vitro and to influence feeding behavior in vivo in rodents. We found that α-MSH-reactive IgG were low in obese but increased in anorectic and bulimic patients and displayed different epitope and kinetics of IC formation. Importantly, while α-MSH/IgG IC from all subjects were binding and activating MC4R, the receptor binding affinity was decreased in obesity. Additionally, α-MSH/IgG IC had lower MC4R-mediated cAMP activation threshold as compared with α-MSH alone in all but not obese subjects. Furthermore, the cellular internalization rate of α-MSH/IgG IC by MC4R-expressing cells was decreased in obese but increased in patients with anorexia nervosa. Moreover, IgG from obese patients prevented central anorexigenic effect of α-MSH. These findings reveal that MC4R is physiologically activated by IC formed by α-MSH/IgG and that different levels and molecular properties of α-MSH-reactive IgG underlie biological activity of such IC relevant to altered appetite in obesity and eating disorders.
Autophagic flux blockage in alveolar epithelial cells is essential in silica nanoparticle-induced pulmonary fibrosis
Authors: Zhao Xinyuan , Wei Saisai , Li Zhijian , Lin Chen , Zhu Zhenfeng , Sun Desen , Bai Rongpan , Qian Jun , Gao Xiangwei , Chen Guangdi , Xu Zhengping
Published: February 2019

Silica nanoparticles (SiNPs) have been reported to induce pulmonary fibrosis (PF) with an unknown mechanism. Recently, the activation of autophagy, a lysosome-dependent cell degradation pathway, by SiNPs has been identified in alveolar epithelial cells (AECs). However, the underlying mechanism and the relevance of SiNPs-induced autophagy to the development of PF remain elusive. Here, we report that autophagy dysfunction and subsequent apoptosis in AECs are involved in SiNPs-induced PF. SiNPs engulfed by AECs enhance autophagosome accumulation and apoptosis both in vivo and in vitro. Mechanically, SiNPs block autophagy flux through impairing lysosomal degradation via acidification inhibition. Lysosomal reacidification by cyclic-3′,5′-adenosine monophosphate (cAMP) significantly enhances autophagic degradation and attenuate apoptosis. Importantly, enhancement of autophagic degradation by rapamycin protects AECs from apoptosis and attenuates SiNPs-induced PF in the mouse model. Altogether, our data demonstrate a repressive effect of SiNPs on lysosomal acidification, contributing to the decreased autophagic degradation in AECs, thus leading to apoptosis and subsequent PF. These findings may provide an improved understanding of SiNPs-induced PF and molecular targets to antagonize it.
Hemi-methylated CpG sites connect Dnmt1-knockdown-induced and Tet1-induced DNA demethylation during somatic cell reprogramming
Authors: He Songwei , Wang Fuhui , Zhang Yixin , Chen Jinlong , Liang Lining , Li Yuan , Zhang Mengdan , Yang Xiao , Pang Hongshen , Li Yingying , Huang Xiaofen , Qin Dajiang , Pei Duanqing , Sun Hao , Zheng Hui
Published: February 2019

The relationship between active DNA demethylation induced by overexpressing Tet1 and passive DNA demethylation induced by suppressing Dnmt1 remains unclear. Here, we found that DNMT1 preferentially methylated, but TET1 preferentially demethylated, hemi-methylated CpG sites. These phenomena resulted in a significant overlap in the targets of these two types of DNA demethylation and the counteractions of Dnmt1 and Tet1 during somatic cell reprogramming. Since the hemi-methylated CpG sites generated during cell proliferation were enriched at core pluripotency loci, DNA demethylation induced by Tet1 or sh-RNA against Dnmt1 (sh-Dnmt1) was enriched in these loci, which, in combination with Yamanaka factors, led to the up-regulation of these genes and promoted somatic cell reprogramming. In addition, since sh-Dnmt1 induces DNA demethylation by impairing the further methylation of hemi-methylated CpG sites generated during cell proliferation, while Tet1 induced DNA demethylation by demethylating these hemi-methylated CpG sites, Tet1-induced DNA demethylation, compared with sh-Dnmt1-induced DNA demethylation, exhibited a higher ability to open the chromatin structure and up-regulate gene expression. Thus, Tet1-induced but not sh-Dnmt1-induced DNA demethylation led to the up-regulation of an additional set of genes that can promote the epithelial-mesenchymal transition and impair reprogramming. When vitamin C was used to further increase the demethylation ability of TET1 during reprogramming, Tet1 induced a larger up-regulation of these genes and significantly impaired reprogramming. Therefore, the current studies provide additional information regarding DNA demethylation during somatic cell reprogramming.
Contemporary climatic analogs for 540 North American urban areas in the late 21st century
Authors: Fitzpatrick Matthew C. , Dunn Robert R.
Published: February 2019

A major challenge in articulating human dimensions of climate change lies in translating global climate forecasts into impact assessments that are intuitive to the public. Climate-analog mapping involves matching the expected future climate at a location (e.g., a person’s city of residence) with current climate of another, potentially familiar, location - thereby providing a more relatable, place-based assessment of climate change. For 540 North American urban areas, we used climate-analog mapping to identify the location that has a contemporary climate most similar to each urban area’s expected 2080’s climate. We show that climate of most urban areas will shift considerably and become either more akin to contemporary climates hundreds of kilometers away and mainly to the south or will have no modern equivalent. Combined with an interactive web application, we provide an intuitive means of raising public awareness of the implications of climate change for 250 million urban residents.
Whole-genome sequencing identifies ADGRG6 enhancer mutations and FRS2 duplications as angiogenesis-related drivers in bladder cancer
Authors: Wu Song , Ou Tong , Xing Nianzeng , Lu Jiang , Wan Shengqing , Wang Changxi , Zhang Xi , Yang Feiya , Huang Yi , Cai Zhiming
Published: February 2019

Bladder cancer is one of the most common and highly vascularized cancers. To better understand its genomic structure and underlying etiology, we conduct whole-genome and targeted sequencing in urothelial bladder carcinomas (UBCs, the most common type of bladder cancer). Recurrent mutations in noncoding regions affecting gene regulatory elements and structural variations (SVs) leading to gene disruptions are prevalent. Notably, we find recurrentADGRG6enhancer mutations andFRS2duplications which are associated with higher protein expression in the tumor and poor prognosis. Functional assays demonstrate that depletion ofADGRG6orFRS2expression in UBC cells compromise their abilities to recruit endothelial cells and induce tube formation. Moreover, pathway assessment reveals recurrent alterations in multiple angiogenesis-related genes. These results illustrate a multidimensional genomic landscape that highlights noncoding mutations and SVs in UBC tumorigenesis, and suggest ADGRG6 and FRS2 as novel pathological angiogenesis regulators that would facilitate vascular-targeted therapies for UBC.
Direct solution-phase synthesis of 1T’ WSe2 nanosheets
Authors: Sokolikova Maria S. , Sherrell Peter C. , Palczynski Pawel , Bemmer Victoria L. , Mattevi Cecilia
Published: February 2019

Crystal phase control in layered transition metal dichalcogenides is central for exploiting their different electronic properties. Access to metastable crystal phases is limited as their direct synthesis is challenging, restricting the spectrum of reachable materials. Here, we demonstrate the solution phase synthesis of the metastable distorted octahedrally coordinated structure (1T’ phase) of WSe2 nanosheets. We design a kinetically-controlled regime of colloidal synthesis to enable the formation of the metastable phase. 1T’ WSe2 branched few-layered nanosheets are produced in high yield and in a reproducible and controlled manner. The 1T’ phase is fully convertible into the semiconducting 2H phase upon thermal annealing at 400 °C. The 1T’ WSe2 nanosheets demonstrate a metallic nature exhibited by an enhanced electrocatalytic activity for hydrogen evolution reaction as compared to the 2H WSe2 nanosheets and comparable to other 1T’ phases. This synthesis design can potentially be extended to different materials providing direct access of metastable phases.
Publisher Correction: Migration alters oscillatory dynamics and promotes survival in connected bacterial populations
Authors: Gokhale Shreyas , Conwill Arolyn , Ranjan Tanvi , Gore Jeff
Published: February 2019

In the original version of this Article, an additional double-headed arrow was inadvertently included within Fig. 3e. This error has been corrected in both the PDF and HTML versions of the Article.
Direct dehydrogenative alkyl Heck-couplings of vinylarenes with umpolung aldehydes catalyzed by nickel
Authors: Lv Leiyang , Zhu Dianhu , Li Chao-Jun
Published: February 2019

Alkenes are fundamental functionalities in nature and highly useful intermediates in organic synthesis, medicinal chemistry and material sciences. Transition-metal-catalyzed Heck couplings with organic halides as electrophiles have been established as a powerful protocol for the synthesis of this valuable building block. However, the requirement of organic halides and the generation of stoichiometric hazardous halide wastes may cause significant sustainable concerns. The halide-free oxidative Heck alkenylations involving organometallics or arenes as the coupling partners provide a facile and alternative pathway. Nonetheless, stoichiometric amounts of extra oxidant are essential in most cases. Herein, we present a direct dehydrogenative alkyl Heck-coupling reaction under oxidant-free conditions, liberating hydrogen, nitrogen and water as the side products. Excellent regioselectivity is achieved via neighboring oxygen atom coordination. Broad substrate scope, great functional group (ketone, ester, phenol, free amine, amide etc) tolerance and modification of pharmaceutical candidates and biological molecules exemplified its generality and practicability.
Quantum magnetisms in uniform triangular lattices Li2AMo3O8 (A = In, Sc)
Authors: Iida Kazuki , Yoshida Hiroyuki , Okabe Hirotaka , Katayama Naoyuki , Ishii Yuto , Koda Akihiro , Inamura Yasuhiro , Murai Naoki , Ishikado Motoyuki , Kadono Ryosuke , Kajimoto Ryoichi
Published: February 2019

Molecular based spin-1/2 triangular lattice systems such as LiZn2Mo3O8 have attracted research interest. Distortions, defects, and intersite disorder are suppressed in such molecular-based magnets, and intrinsic geometrical frustration gives rise to unconventional and unexpected ground states. Li2AMo3O8 (A = In or Sc) is such a compound where spin-1/2 Mo3O13 clusters in place of Mo ions form the uniform triangular lattice. Their ground states are different according to the A site. Li2InMo3O8 undergoes conventional 120° long-range magnetic order below TN = 12 K whereas isomorphic Li2ScMo3O8 exhibits no long-range magnetic order down to 0.5 K. Here, we report exotic magnetisms in Li2InMo3O8 and Li2ScMo3O8 investigated by muon spin rotation (μSR) and inelastic neutron scattering (INS) spectroscopies using polycrystalline samples. Li2InMo3O8 and Li2ScMo3O8 show completely different behaviors observed in both μSR and INS measurements, representing their different ground states. Li2InMo3O8 exhibits spin wave excitation which is quantitatively described by the nearest neighbor anisotropic Heisenberg model based on the 120° spin structure. In contrast, Li2ScMo3O8 undergoes short-range magnetic order below 4 K with quantum-spin-liquid-like magnetic fluctuations down to the base temperature. Origin of the different ground states is discussed in terms of anisotropies of crystal structures and magnetic interactions.
Cardiac fibroblast activation and hyaluronan synthesis in response to hyperglycemia and diet-induced insulin resistance
Authors: Gorski Daniel J. , Petz Anne , Reichert Christina , Twarock Sören , Grandoch Maria , Fischer Jens W.
Published: February 2019

Diabetic patients are at a greater risk of heart failure due to diabetic cardiomyopathy and worsened outcome post-myocardial infarction. While the molecular mechanisms remain unclear, fibrosis and chronic inflammation are common characteristics of both conditions. Diabetes mellitus (types I and II) results in excessive hyaluronan (HA) deposition in vivo, and hyperglycemia stimulates HA synthesis for several cell types in vitro. HA-rich extracellular matrix contributes to fibrotic, hyperplastic and inflammatory disease progression. We hypothesized that excessive hyperglycemia-driven HA accumulation may contribute to pathological fibroblast activation and fibrotic remodelling in diabetic patients. Therefore, we analysed the impact of both hyperglycemia and diet-induced obesity and insulin resistance on HA matrix formation and cardiac fibroblast activation. Here we report that cardiac fibroblasts isolated from mice on a diabetogenic diet acquire pro-fibrotic gene expression without a concomitant increase in HA matrix deposition. Additionally, hyperglycemia alone does not stimulate HA synthesis or cardiac fibroblast activation in vitro, suggesting that the direct effect of hyperglycemia on fibroblasts is not the primary driver of fibrotic remodelling in cardiac diabetic maladaptation.
Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data
Authors: Mistry Akshitkumar M. , Wooten David J. , Davis L. Taylor , Mobley Bret C. , Quaranta Vito , Ihrie Rebecca A.
Published: February 2019

Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ − GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ − GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. TCGA molecular data analyses revealed that VSVZ contact by GBM was independent of mutational, DNA methylation, gene expression, and protein expression signatures in the bulk tumor. Therefore, while survival of GBM patients is independently stratified by VSVZ contact, with VSVZ + GBM patients displaying a poor prognosis, the VSVZ + GBMs do not possess a distinct molecular signature at the bulk sample level. Focused examination of the interplay between the VSVZ microenvironment and subsets of GBM cells proximal to this region is warranted.
Catalytic preparation of levulinic acid from cellobiose via Brønsted-Lewis acidic ionic liquids functional catalysts
Authors: Liu Shiwei , Wang Kai , Yu Hailong , Li Binghan , Yu Shitao
Published: February 2019

Brønsted-Lewis acidic ionic liquids (ILs) were applied to catalyze cellobiose to prepare levulinic acid (LA) in one pot under hydrothermal conditions. Under the optimum conditions, the highest LA yield of 67.51% was obtained when low [HO3S-(CH2)3-mim]Cl-FeCl3 (molar fraction of FeCl3 x = 0.60) was used. This indicated the Brønsted-Lewis acidic ILs played an active role in the conversion of cellobiose to LA. The catalytic mechanism of ILs had been established, disclosing that the Brønsted-Lewis acidic ILs had the catalytic synergistic effect originating from its double acid sites. During the reaction process, the Lewis acid sites improved the isomerization of glucose to fructose, then the Brønsted and Lewis acid sites simultaneously enhanced the dehydration of fructose to produce hydroxymethylfurfural (HMF), which was propitious to the synthesize LA with high yield. In addition, LA could be easily extracted by methyl isobutyl ketone (MIBK), and the ILs could retain its basic activity after 5 cycles. The solid residues were characterized using SEM, FT-IR and TG-DTG spectroscopy. It was the conclusion that a large amount of humins were produced during the cellobiose conversion process. In this reaction, the ILs not only overcomes the problems of the conventional catalyst, but also completes the reaction-separation integration and the recycling of the catalyst. This paper provided an important theoretical basis for the application of ILs in the field of biomass.
Distinct Subsets of Lateral Hypothalamic Neurotensin Neurons are Activated by Leptin or Dehydration
Authors: Brown Juliette A. , Wright Anna , Bugescu Raluca , Christensen Lyndsay , Olson David P. , Leinninger Gina M.
Published: February 2019

The lateral hypothalamic area (LHA) is essential for ingestive behavior but it remains unclear how LHA neurons coordinate feeding vs. drinking. Most LHA populations promote food and water consumption but LHA neurotensin (Nts) neurons preferentially induce water intake while suppressing feeding. We identified two molecularly and projection-specified subpopulations of LHA Nts neurons that are positioned to coordinate either feeding or drinking. One subpopulation co-expresses the long form of the leptin receptor (LepRb) and is activated by the anorectic hormone leptin (NtsLepRb neurons). A separate subpopulation lacks LepRb and is activated by dehydration (NtsDehy neurons). These molecularly distinct LHA Nts subpopulations also differ in connectivity: NtsLepRb neurons project to the ventral tegmental area and substantia nigra compacta but NtsDehy neurons do not. Intriguingly, the LHA Nts subpopulations cannot be discriminated via their classical neurotransmitter content, as we found that all LHA Nts neurons are GABAergic. Collectively, our data identify two molecularly- and projection-specified subpopulations of LHA Nts neurons that intercept either leptin or dehydration cues, and which conceivably could regulate feeding vs. drinking behavior. Selective regulation of these LHA Nts subpopulations might be useful to specialize treatment for ingestive disorders such as polydipsia or obesity.
Using Memristors for Robust Local Learning of Hardware Restricted Boltzmann Machines
Authors: Ernoult Maxence , Grollier Julie , Querlioz Damien
Published: February 2019

One of the biggest stakes in nanoelectronics today is to meet the needs of Artificial Intelligence by designing hardware neural networks which, by fusing computation and memory, process and learn from data with limited energy. For this purpose, memristive devices are excellent candidates to emulate synapses. A challenge, however, is to map existing learning algorithms onto a chip: for a physical implementation, a learning rule should ideally be tolerant to the typical intrinsic imperfections of such memristive devices, and local. Restricted Boltzmann Machines (RBM), for their local learning rule and inherent tolerance to stochasticity, comply with both of these constraints and constitute a highly attractive algorithm towards achieving memristor-based Deep Learning. On simulation grounds, this work gives insights into designing simple memristive devices programming protocols to train on chip Boltzmann Machines. Among other RBM-based neural networks, we advocate using a Discriminative RBM, with two hardware-oriented adaptations. We propose a pulse width selection scheme based on the sign of two successive weight updates, and show that it removes the constraint to precisely tune the initial programming pulse width as a hyperparameter. We also propose to evaluate the weight update requested by the algorithm across several samples and stochastic realizations. We show that this strategy brings a partial immunity against the most severe memristive device imperfections such as the non-linearity and the stochasticity of the conductance updates, as well as device-to-device variability.
Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species
Authors: Sharifi R. , Yang Y. , Adibnia Y. , Dohlman C. H. , Chodosh J. , Gonzalez-Andrades M.
Published: February 2019

Numerous animal species have been proposed as sources of corneal tissue for obtaining decellularized xenografts. The selection of an appropriate animal model must take into consideration the differences in the composition and structure of corneal proteins between humans and other animal species in order to minimize immune response and improve outcome of the xenotransplant. Here, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence. Primary amino acid structures, isoelectric point and grand average of hydropathy (GRAVY) values of the 7 most abundant proteins (i.e. collagen α-1 (I), α-1 (VI), α-2 (I) and α-3 (VI), as well as decorin, lumican, and keratocan) were also extracted and compared to those of human. The pig had the highest similarity score (91.8%). All species showed a lower proline content compared to human. Isoelectric point of pig (7.1) was the closest to the human. Most species have higher GRAVY values compared to human except horse. Our results suggest that porcine cornea has a higher relative suitability for corneal transplantation into humans compared to other studied species.
Preoperative platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as predictors of clinical outcome in patients with gallbladder cancer
Authors: Zhu Sha , Yang Jing , Cui Xiwei , Zhao Yunuo , Tao Zhihang , Xia Fan , Chen Linyan , Huang Juan , Ma Xuelei
Published: February 2019

Some inflammatory biomarkers are associated with the post-surgical prognosis in cancer patients. However, their clinical importance in gallbladder cancer has rarely been explored. The aim of this study is to assess the efficacy of surgical intervention and the effectiveness of preoperative test on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) for predicting the prognosis in gallbladder cancer patients. In this study, a total of 255 gallbladder cancer patients were retrospectively selected. For each patient, we recorded his/her treatment algorithm (with or without surgery) and their preoperative inflammatory biomarkers, as well as their detailed survival information for 5 years. A total of 216 patients received surgical intervention and the other 39 chose conservative treatment. The median survival time was 4.6 months for non-surgical group (P < 0.001), and 12.2 months for surgical intervention group. Among the surgical group, ROC analysis showed the AUC of NLR, PLR and MLR were 0.675 (95% CI: 0.600 to 0.751, P < 0.001), 0.599 (95% CI: 0.520 to 0.677, P = 0.017) and 0.607 (95% CI: 0.529 to 0.686, P = 0.009), respectively. In conclusion, surgical intervention did improve the overall survival, and elevated NLR and MLR before surgery are associated with shorter OS of GBC patients.
The genetic Creutzfeldt-Jakob disease with E200K mutation: analysis of clinical, genetic and laboratory features of 30 Chinese patients
Authors: Gao Li-Ping , Shi Qi , Xiao Kang , Wang Jing , Zhou Wei , Chen Cao , Dong Xiao-Ping
Published: February 2019

Genetic Creutzfeldt-Jakob disease (gCJD) with E200K mutation is one of the common subtypes of human genetic prion diseases worldwide. In this study, we systematically analyzed 30 Chinese E200K gCJD cases for their epidemiological, clinical, laboratory and genetic features. The patients came from 12 different provinces, majority in northern part of China. The onset age varied from 42 to 71 year-old (y), with the median of was 57 y. The CYP4X1 gene rs9793471 SNP was tested. Only one patient’s rs9793471 genotype was GA and the others’ were AA. The gender ratio (M: F) was 1:1.73 (11:19). The foremost symptoms and clinical progression of Chinese E200K gCJD patients were quite similar as sporadic CJD cases. Only a few cases (4/30) recalled clearly disease related family history. 74.1% (20/27), 86.7% (26/30) and 50.0% (13/26) of the cases were CSF 14-3-3 positive, sCJD associated abnormalities on MRI and special PSWC on EEG, respectively. The median clinical duration was 9 months (varying from 2 to 26 months). All 30 Chinese E200K gCJD patients were M129M and E219E homozygous. 21 members from 3 families conducted PRNP sequencing and 16 asymptomatic carriers of E200K mutation with M129M and E219E homozygous were identified. This is the largest study on E200K gCJD patients in China, which would benefit to the knowledge of E200K gCJD.
Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9
Authors: Kostyushev Dmitry , Kostyusheva Anastasiya , Brezgin Sergey , Zarifyan Dmitry , Utkina Anastasiya , Goptar Irina , Chulanov Vladimir
Published: February 2019

Chronic hepatitis B is a severe liver disease caused by hepatitis B virus (HBV) infection. Covalently closed circular DNA (cccDNA), a super-spiralized, double-stranded form of the HBV genome, is the major determinant of viral persistence. CRISPR/Cas9 nucleases have been recently shown to introduce double-stranded DNA breaks into HBV cccDNA. The inflicted damage results predominantly in erroneous repair of cccDNA by non-homologous end-joining (NHEJ). NHEJ has been suggested to enhance anti-HBV activity of CRISPR/Cas9 and increase cccDNA mutation. In this study, we assessed anti-HBV activity of CRISPR/Cas9 and cccDNA repair outcomes in an altered NHEJ/HR environment. NU7026, a strong inhibitor of NHEJ, prevented CRISPR/Cas9-mediated degradation of cccDNA and resulted in frequent on-target deletions. We conclude that CRISPR/Cas9 is a highly effective tool to degrade cccDNA and first demonstrate that inhibiting NHEJ impairs cccDNA degradation.
Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models
Authors: Wang Zebin , Sun Kaiming , Xiao Yonghong , Feng Bin , Mikule Keith , Ma XiaoYan , Feng Ningping , Vellano Christopher P. , Federico Lorenzo , Marszalek Joseph R. , Mills Gordon B. , Hanke Jeffrey , Ramaswamy Sridhar , Wang Jing
Published: February 2019

PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and in breast cancers with germline BRCA1/2 mutation. However, resistance to PARP inhibitors may preexist or evolve during treatment in many cancer types and may be overcome by combining PARP inhibitors with other therapies, such as immune checkpoint inhibitors, which confer durable responses and are rapidly becoming the standard of care for multiple tumor types. This study investigated the therapeutic potential of combining niraparib, a highly selective PARP1/2 inhibitor, with anti-PD-1 immune checkpoint inhibitors in preclinical tumor models. Our results indicate that niraparib treatment increases the activity of the type I (alpha) and type II (gamma) interferon pathways and enhances the infiltration of CD8+ cells and CD4+ cells in tumors. When coadministered in immunocompetent models, the combination of niraparib and anti-PD-1 demonstrated synergistic antitumor activities in both BRCA-proficient and BRCA-deficient tumors. Interestingly, mice with tumors cured by niraparib monotherapy completely rejected tumor growth upon rechallenge with the same tumor cell line, suggesting the potential establishment of immune memory in animals treated with niraparib monotherapy. Taken together, our findings uncovered immunomodulatory effects of niraparib that may sensitize tumors to immune checkpoint blockade therapies.
Development of a suicide index model in general adolescents using the South Korea 2012–2016 national representative survey data
Authors: Lee Jinhee , Jang Ho , Kim Jongkoo , Min Seongho
Published: February 2019

Suicide is a leading cause of death among adolescents and a major public health concern. Here we developed a risk stratification model for adolescent suicide attempts using sociodemographic characteristics, risk behaviours and psychological variables. Participants were 247,222 subjects in the Korea Youth Risk Behavior Web-based Survey (KYRBS). We developed a suicide index based on the suicide risk estimated in the generalized linear model and proposed the risk stratification model using the R language to measure the probability of suicide attempt among adolescents. Among the study population, the annual rate of suicide attempt was approximately 4%. The model provided good prediction for suicide attempt (AUC = 0.85). The important univariate risk factors for the outcome were dimensional measures of age, sex, breakfast consumption, experience of violence, sleep duration, perceived stress, feeling of sadness, current cigarette smoking, current alcohol drinking, perceived general health, perceived academic record, household economic status and living with biological or adoptive parents. Our suicide index model allowed the identification of adolescents who are at a high risk for suicide. This tool may promote the prevention of adolescent suicide and can be particularly useful in everyday settings where it is difficult to contact mental health professionals immediately.