bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of initiating moderate wine intake on abdominal adipose tissue in adults with type 2 diabetes: a 2-year randomized controlled trial
Authors: Golan Rachel , Shelef Ilan , Shemesh Elad , Henkin Yaakov , Schwarzfuchs Dan , Gepner Yftach , Harman-Boehm Ilana , Witkow Shula , Friger Michael , Chassidim Yoash , Liberty Idit F , Sarusi Benjamin , Serfaty Dana , Bril Nitzan , Rein Michal , Cohen Noa , Ben-Avraham Sivan , Ceglarek Uta , Stumvoll Michael , Blüher Matthias , Thiery Joachim , Stampfer Meir J , Rudich Assaf , Shai Iris
Published: October 2016

Objective

To generate evidence-based conclusions about the effect of wine consumption on weight gain and abdominal fat accumulation and distribution in patients with type 2 diabetes.

Design

In the 2-year randomized controlled CASCADE (CArdiovaSCulAr Diabetes & Ethanol) trial, patients following a Mediterranean diet were randomly assigned to drink 150 ml of mineral water, white wine or red wine with dinner for 2 years. Visceral adiposity and abdominal fat distribution were measured in a subgroup of sixty-five participants, using abdominal MRI.

Setting

Ben-Gurion University of the Negev, Soroka-Medical Center and the Nuclear Research Center Negev, Israel.

Subjects

Alcohol-abstaining adults with well-controlled type 2 diabetes.

Results

Forty-eight participants (red wine, n 27; mineral water, n 21) who completed a second MRI measurement were included in the 2-year analysis. Similar weight losses (sd) were observed: red wine 1·3 (3·9) kg; water 1·0 (4·2) kg (P=0·8 between groups). Changes (95 % CI) in abdominal adipose-tissue distribution were similar: red wine, visceral adipose tissue (VAT) −3·0 (−8·0, 2·0) %, deep subcutaneous adipose tissue (DSAT) +5·2 (−1·1, 11·6) %, superficial subcutaneous adipose tissue (SSAT) −1·9 (−5·0, 1·2) %; water, VAT −3·2 (−8·9, 2·5) %, DSAT +2·9 (−2·8, 8·6) %, SSAT −0·15 (−3·3, 2·9) %. No changes in antidiabetic medication and no substantial changes in energy intake (+126 (sd 2889) kJ/d (+30·2 (sd 690) kcal/d), P=0·8) were recorded. A 2-year decrease in glycated Hb (β=0·28, P=0·05) was associated with a decrease in VAT.

Conclusions

Moderate wine consumption, as part of a Mediterranean diet, in persons with controlled diabetes did not promote weight gain or abdominal adiposity.
Does pension privatization increase economic growth? Evidence from Latin America and Eastern Europe
Authors: ALTIPARMAKOV NIKOLA , NEDELJKOVIĆ MILAN
Published: October 2016

Analyses of pension funding effects on economic growth should differentiate between ‘carve-out’ pension privatization in Latin America and Eastern Europe and typical ‘add-on’ pension funding in Western Europe and North America. We find no evidence that pension privatization in Latin America and Eastern Europe was associated with higher economic growth. The result is robust across both continents and several alternative econometric specifications. Positive growth effects are particularly unlikely in countries resorting to debt-financed privatization. Furthermore, we note the lack of positive pension privatization effects on savings in Eastern Europe, with limited evidence of positive savings effects in Latin America. These findings suggest that cost-containment parametric reforms should be given priority over carve-out pension privatization when considering options for restoring financial sustainability of public Pay-As-You-Go systems.
Organic and conventional farmers differ in their perspectives on cover crop use and breeding
Authors: Wayman Sandra , Kissing Kucek Lisa , Mirsky Steven B. , Ackroyd Victoria , Cordeau Stéphane , Ryan Matthew R.
Published: October 2016

Cover crops play an important role in agricultural sustainability. Unlike commodity cash crops, however, there has been relatively little cover crop breeding research and development. We conducted an online survey to evaluate: (a) the perspectives of organic and conventional farmers in the USA who use cover crops and (b) the specific cover crop traits that are important to farmers. We recruited participants from both organic and conventional agriculture networks and 69% of respondents reported that they farmed organic land. In addition to demographic data and information on management practices, we quantified farmer perspectives on four winter annual cover crops: (1) Austrian winter pea, (2) crimson clover, (3) hairy vetch and (4) cereal rye. Overall, respondents represented a wide range of states, farm sizes, plant hardiness zones and cash crops produced. Of the 417 full responses received, 87% of respondents reported that they used cover crops. The maximum amount farmers were willing to spend on cover crop seed varied by farmer type: 1% of conventional farmers versus 19% of organic farmers were willing to spend over US$185 ha−1(US$75 acre−1). Organic and conventional farmers differed in terms of the reasons why they grew cover crops, with organic farmers placing greater value on the ecosystem services from cover crops. More organic (63%) than conventional (51%) farmers agreed that participatory breeding was important for cover crop variety development (P= 0.047). Both groups shared strong support for cover crop research and considered many of the same traits to be important for breeding. For the legume cover crops, nitrogen fixation was considered the most important trait, whereas winter hardiness, early vigor, biomass production and weed suppression were the most important traits for cereal rye. Our results illustrate common interests as well as differences in the perspectives between organic and conventional farmers on cover crops and can be used to inform nascent cover crop breeding efforts.
The Posttraumatic Growth Inventory: Factor Structure and Invariance in a Sample of Breast Cancer Patients and in a Non-Clinical Sample
Authors: Ramos Catarina , Leal Isabel , Marôco Ana Lúcia , Tedeschi Richard G.
Published: October 2016

The Posttraumatic Growth Inventory (PTGI) is frequently used to assess positive changes following a traumatic event. The aim of the study is to examine the factor structure and the latent mean invariance of PTGI. A sample of 205 (Mage = 54.3, SD = 10.1) women diagnosed with breast cancer and 456 (Mage = 34.9, SD = 12.5) adults who had experienced a range of adverse life events were recruited to complete the PTGI and a socio-demographic questionnaire. We use Confirmatory Factor Analysis (CFA) to test the factor-structure and multi-sample CFA to examine the invariance of the PTGI between the two groups. The goodness of fit for the five-factor model is satisfactory for breast cancer sample (χ2(175) = 396.265; CFI = .884; NIF = .813; RMSEA [90% CI] = .079 [.068, .089]), and good for non-clinical sample (χ2(172) = 574.329; CFI = .931; NIF = .905; RMSEA [90% CI] = .072 [.065, .078]). The results of multi-sample CFA show that the model fit indices of the unconstrained model are equal but the model that uses constrained factor loadings is not invariant across groups. The findings provide support for the original five-factor structure and for the multidimensional nature of posttraumatic growth (PTG). Regarding invariance between both samples, the factor structure of PTGI and other parameters (i.e., factor loadings, variances, and co-variances) are not invariant across the sample of breast cancer patients and the non-clinical sample.
Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells
Authors: Lin C-Y , Chang T-W , Hsieh W-H , Hung M-C , Lin I-H , Lai S-C , Tzeng Y-J
Published: October 2016

Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIPS) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIPS is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIPS, consequently causes FLIPS to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIPS levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIPS regulation-mediated apoptosis/necroptosis, which has not been previously documented. Moreover, the involvement of the cleavage type of MLKL in executing necroptosis warrants further investigation.
Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants
Authors: Ploier Birgit , Caro Lydia N. , Morizumi Takefumi , Pandey Kalpana , Pearring Jillian N. , Goren Michael A. , Finnemann Silvia C. , Graumann Johannes , Arshavsky Vadim Y. , Dittman Jeremy S. , Ernst Oliver P. , Menon Anant K.
Published: October 2016

Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin’s activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations—F45L, V209M and F220C—yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.
A 17 GHz molecular rectifier
Authors: Trasobares J. , Vuillaume D. , Théron D. , Clément N.
Published: October 2016

Molecular electronics originally proposed that small molecules sandwiched between electrodes would accomplish electronic functions and enable ultimate scaling to be reached. However, so far, functional molecular devices have only been demonstrated at low frequency. Here, we demonstrate molecular diodes operating up to 17.8 GHz. Direct current and radio frequency (RF) properties were simultaneously measured on a large array of molecular junctions composed of gold nanocrystal electrodes, ferrocenyl undecanethiol molecules and the tip of an interferometric scanning microwave microscope. The present nanometre-scale molecular diodes offer a current density increase by several orders of magnitude compared with that of micrometre-scale molecular diodes, allowing RF operation. The measured S11 parameters show a diode rectification ratio of 12 dB which is linked to the rectification behaviour of the direct current conductance. From the RF measurements, we extrapolate a cut-off frequency of 520 GHz. A comparison with the silicon RF-Schottky diodes, architecture suggests that the RF-molecular diodes are extremely attractive for scaling and high-frequency operation.
Histone variant H3F3A promotes lung cancer cell migration through intronic regulation
Authors: Park Seong-Min , Choi Eun-Young , Bae Mingyun , Kim Sunshin , Park Jong Bae , Yoo Heon , Choi Jung Kyoon , Kim Youn-Jae , Lee Seung-Hoon , Kim In-Hoo
Published: October 2016

Although several somatic single nucleotide variations in histone H3.3 have been investigated as cancer drivers, other types of aberration have not been well studied. Here, we demonstrate that overexpression of H3F3A, encoding H3.3, is associated with lung cancer progression and promotes lung cancer cell migration by activating metastasis-related genes. H3.3 globally activates gene expression through the occupation of intronic regions in lung cancer cells. Moreover, H3.3 binding regions show characteristics of regulatory DNA elements. We show that H3.3 is deposited at a specific intronic region of GPR87, where it modifies the chromatin status and directly activates GPR87 transcription. The expression levels of H3F3A and GPR87, either alone or in combination, are robust prognostic markers for early-stage lung cancer, and may indicate potential for the development of treatments involving GPR87 antagonists. In summary, our results demonstrate that intronic regulation by H3F3A may be a target for the development of novel therapeutic strategies.
N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi
Authors: Su Chang , Lu Yang , Liu Haoping
Published: October 2016

N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans. Many fungi are able to utilize environmental GlcNAc to support growth and induce cellular development, a property important for their survival in various host niches. However, how the GlcNAc signal is sensed and subsequently transduced is largely unknown. Here, we identify a gene that is essential for GlcNAc signalling (NGS1) in Candida albicans, a commensal and pathogenic yeast of humans. Ngs1 can bind GlcNAc through the N-terminal β-N-acetylglucosaminidase homology domain. This binding activates N-acetyltransferase activity in the C-terminal GCN5-related N-acetyltransferase domain, which is required for GlcNAc-induced promoter histone acetylation and transcription. Ngs1 is targeted to the promoters of GlcNAc-inducible genes constitutively by the transcription factor Rep1. Ngs1 is conserved in diverse fungi that have GlcNAc catabolic genes. Thus, fungi use Ngs1 as a GlcNAc-sensor and transducer for GlcNAc-induced transcription.
Projection-type see-through holographic three-dimensional display
Authors: Wakunami Koki , Hsieh Po-Yuan , Oi Ryutaro , Senoh Takanori , Sasaki Hisayuki , Ichihashi Yasuyuki , Okui Makoto , Huang Yi-Pai , Yamamoto Kenji
Published: October 2016

Owing to the limited spatio-temporal resolution of display devices, dynamic holographic three-dimensional displays suffer from a critical trade-off between the display size and the visual angle. Here we show a projection-type holographic three-dimensional display, in which a digitally designed holographic optical element and a digital holographic projection technique are combined to increase both factors at the same time. In the experiment, the enlarged holographic image, which is twice as large as the original display device, projected on the screen of the digitally designed holographic optical element was concentrated at the target observation area so as to increase the visual angle, which is six times as large as that for a general holographic display. Because the display size and the visual angle can be designed independently, the proposed system will accelerate the adoption of holographic three-dimensional displays in industrial applications, such as digital signage, in-car head-up displays, smart-glasses and head-mounted displays.
Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers
Authors: Kim Jin-Ah , Tan Ying , Wang Xian , Cao Xixi , Veeraraghavan Jamunarani , Liang Yulong , Edwards Dean P. , Huang Shixia , Pan Xuewen , Li Kaiyi , Schiff Rachel , Wang Xiao-Song
Published: October 2016

More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast cancers remain a great clinical challenge. Here our integrative genomic analysis identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently amplified in ∼10.5% of ER-positive breast tumours. The resulting overexpression of TLK2 is more significant in aggressive and advanced tumours, and correlates with worse clinical outcome regardless of endocrine therapy. Ectopic expression of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively inhibits the growth of TLK2-high breast cancer cells, downregulates ERα, BCL2 and SKP2, impairs G1/S cell cycle progression, induces apoptosis and significantly improves progression-free survival in vivo. We identify two potential TLK2 inhibitors that could serve as backbones for future drug development. Together, amplification of the cell cycle kinase TLK2 presents an attractive genomic target for aggressive ER-positive breast cancers.
The backtracking survey propagation algorithm for solving random K-SAT problems
Authors: Marino Raffaele , Parisi Giorgio , Ricci-Tersenghi Federico
Published: October 2016

Discrete combinatorial optimization has a central role in many scientific disciplines, however, for hard problems we lack linear time algorithms that would allow us to solve very large instances. Moreover, it is still unclear what are the key features that make a discrete combinatorial optimization problem hard to solve. Here we study random K-satisfiability problems with K=3,4, which are known to be very hard close to the SAT-UNSAT threshold, where problems stop having solutions. We show that the backtracking survey propagation algorithm, in a time practically linear in the problem size, is able to find solutions very close to the threshold, in a region unreachable by any other algorithm. All solutions found have no frozen variables, thus supporting the conjecture that only unfrozen solutions can be found in linear time, and that a problem becomes impossible to solve in linear time when all solutions contain frozen variables.
EIN2-dependent regulation of acetylation of histone H3K14 and non-canonical histone H3K23 in ethylene signalling
Authors: Zhang Fan , Qi Bin , Wang Likai , Zhao Bo , Rode Siddharth , Riggan Nathaniel D. , Ecker Joseph R. , Qiao Hong
Published: October 2016

Ethylene gas is essential for many developmental processes and stress responses in plants. EIN2 plays a key role in ethylene signalling but its function remains enigmatic. Here, we show that ethylene specifically elevates acetylation of histone H3K14 and the non-canonical acetylation of H3K23 in etiolated seedlings. The up-regulation of these two histone marks positively correlates with ethylene-regulated transcription activation, and the elevation requires EIN2. Both EIN2 and EIN3 interact with a SANT domain protein named EIN2 nuclear associated protein 1 (ENAP1), overexpression of which results in elevation of histone acetylation and enhanced ethylene-inducible gene expression in an EIN2-dependent manner. On the basis of these findings we propose a model where, in the presence of ethylene, the EIN2 C terminus contributes to downstream signalling via the elevation of acetylation at H3K14 and H3K23. ENAP1 may potentially mediate ethylene-induced histone acetylation via its interactions with EIN2 C terminus.
A universal test for gravitational decoherence
Authors: Pfister C. , Kaniewski J. , Tomamichel M. , Mantri A. , Schmucker R. , McMahon N. , Milburn G. , Wehner S.
Published: October 2016

Quantum mechanics and the theory of gravity are presently not compatible. A particular question is whether gravity causes decoherence. Several models for gravitational decoherence have been proposed, not all of which can be described quantum mechanically. Since quantum mechanics may need to be modified, one may question the use of quantum mechanics as a calculational tool to draw conclusions from the data of experiments concerning gravity. Here we propose a general method to estimate gravitational decoherence in an experiment that allows us to draw conclusions in any physical theory where the no-signalling principle holds, even if quantum mechanics needs to be modified. As an example, we propose a concrete experiment using optomechanics. Our work raises the interesting question whether other properties of nature could similarly be established from experimental observations alone—that is, without already having a rather well-formed theory of nature to make sense of experimental data.
The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway
Authors: Mai H , Xu X , Mei G , Hong T , Huang J , Wang T , Yan Z , Li Y , Liang Y , Li L , Jin S , You W , Ma Y , Chen L , Ye Q
Published: October 2016

Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to be crucial during the development and progression of a variety of tumors. However, the role of HPIP in renal cell carcinoma (RCC) is unknown. Here we report that HPIP is upregulated in most RCC patients, positively correlates with tumor size, high Fuhrman grade and preoperative metastasis, and predicts poor clinical outcomes. Mechanistically, we identified casein kinase 1α (CK1α), a critical regulator of tumorigenesis and metastasis, as a novel HPIP-interacting protein. HPIP facilitates RCC cell growth, migration, invasion and epithelial–mesenchymal transition depending on its interaction with CK1α. Activation of mammalian target of rapamycin pathways by HPIP is partly dependent on CK1α and is required for HPIP modulation of RCC cell proliferation and migration. HPIP knockdown suppresses renal tumor growth and metastasis in nude mice through CK1α. Moreover, expression of CK1α is positively correlated with HPIP in RCC samples, and also predicts poor clinical outcome-like expression of HPIP. Taken together, our data demonstrate the critical regulatory role of the HPIP–CK1α interaction in RCC, and suggest that HPIP and CK1α may be potential targets for RCC therapy.
DUOX1 silencing in lung cancer promotes EMT, cancer stem cell characteristics and invasive properties
Authors: Little A C , Sham D , Hristova M , Danyal K , Heppner D E , Bauer R A , Sipsey L M , Habibovic A , van der Vliet A
Published: October 2016

Dual oxidase 1 (DUOX1) is an oxidant-generating enzyme within the airway epithelium that participates in innate airway host defense and epithelial homeostasis. Recent studies indicate that DUOX1 is suppressed in lung cancers by epigenetic silencing, although the importance of DUOX1 silencing in lung cancer development or progression is unknown. Here we show that loss of DUOX1 expression in a panel of lung cancer cell lines is strongly associated with loss of the epithelial marker E-cadherin. Moreover, RNAi-mediated DUOX1 silencing in lung epithelial cells and the cancer cell line NCI-H292 was found to result in loss of epithelial characteristics/molecular features (altered morphology, reduced barrier function and loss of E-cadherin) and increased mesenchymal features (increased migration, anchorage-independent growth and gain of vimentin/collagen), suggesting a direct contribution of DUOX1 silencing to epithelial-to-mesenchymal transition (EMT), an important feature of metastatic cancer. Conversely, overexpression of DUOX1 in A549 cells was capable of reversing EMT features. DUOX1 silencing in H292 cells also led to enhanced resistance to epidermal growth factor receptor tyrosine kinase inhibitors such as erlotinib, and enhanced levels of cancer stem cell (CSC) markers CD133 and ALDH1. Furthermore, acquired resistance of H292 cells to erlotinib resulted in enhanced EMT and CSC features, as well as loss of DUOX1. Finally, compared with control H292 cells, H292-shDUOX1 cells displayed enhanced invasive features in vitro and in vivo. Collectively, our findings indicate that DUOX1 silencing in lung epithelial cancer cells promotes features of EMT, and may be strongly associated with invasive and metastatic lung cancer.
The site of water stress governs the pattern of ABA synthesis and transport in peanut
Authors: Hu Bo , Cao Jiajia , Ge Kui , Li Ling
Published: October 2016

Abscisic acid (ABA) is one of the most important phytohormones involved in stress responses in plants. However, knowledge of the effect on ABA distribution and transport of water stress at different sites on the plant is limited. In this study, water stress imposed on peanut leaves or roots by treatment with PEG 6000 is termed “leaf stress” or “root stress”, respectively. Immunoenzyme localization technolony was first used to detect ABA distribution in peanut. Under root stress, ABA biosynthesis and distribution level were all more pronounced in root than in leaf. However, ABA transport and the ability to induce stomatal closure were still better in leaf than in root during root stress; However, ABA biosynthesis initially increased in leaf, then rapidly accumulated in the vascular cambium of leaves and induced stomatal closure under leaf stress; ABA produced in root tissues was also transported to leaf tissues to maintain stomatal closure. The vascular system was involved in the coordination and integration of this complex regulatory mechanism for ABA signal accumulation. Water stress subject to root or leaf results in different of ABA biosynthesis and transport ability that trigger stoma close in peanut.
Dairy and plant based food intakes are associated with altered faecal microbiota in 2 to 3 year old Australian children
Authors: Smith-Brown P. , Morrison M. , Krause L. , Davies P. S. W.
Published: October 2016

The first 1000 days (conception to 24 months) is when gut microbiota composition and eating patterns are established, and a critical period influencing lifelong health. The aim of this study is to examine the associations between food intakes and microbiota composition at the end of this period. Diet was quantified for 37 well-nourished Australian children aged between 2 to 3 years by using a food frequency questionnaire and 24 hr recalls. Both dairy and plant-based (fruit, vegetables, soy, pulses and nuts) food intakes were associated with distinct microbiota profiles. Dairy intake was positively associated with the Firmicutes:Bacteroidetes ratio, and in particular Erysipelatoclostridium spp., but negatively associated with species richness and diversity. Vegetable intake was positively associated with the relative abundance of the Lachnospira genus, while soy, pulse and nut intake was positively associated with the relative abundance of bacteria related to Bacteroides xylanisolvens. Fruit intake, especially apples and pears, were negatively associated with the relative abundance of bacteria related to Ruminococcus gnavus. In this cohort of young children dairy and plant based food intakes were found to be associated with altered microbiota composition. Further exploration is needed to elucidate the effect of these dietary and microbial differences on host phenotype.
Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border
Authors: Wang Zenglei , Cabrera Mynthia , Yang Jingyun , Yuan Lili , Gupta Bhavna , Liang Xiaoying , Kemirembe Karen , Shrestha Sony , Brashear Awtum , Li Xiaolian , Porcella Stephen F. , Miao Jun , Yang Zhaoqing , Su Xin-zhuan , Cui Liwang
Published: October 2016

Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide association studies, we investigated the associations of genome-wide single nucleotide polymorphisms with in vitro sensitivities to 10 commonly used antimalarial drugs in 94 P. falciparum isolates from the China-Myanmar border area, a region with the longest history of ART usage. We identified several loci associated with various drugs, including those containing pfcrt and pfdhfr. Of particular interest is a locus on chromosome 10 containing the autophagy-related protein 18 (ATG18) associated with decreased sensitivities to dihydroartemisinin, artemether and piperaquine – an ACT partner drug in this area. ATG18 is a phosphatidylinositol-3-phosphate binding protein essential for autophagy and recently identified as a potential ART target. Further investigations on the ATG18 and genes at the chromosome 10 locus may provide an important lead for a connection between ART resistance and autophagy.
Default mode network and frontolimbic gray matter abnormalities in patients with borderline personality disorder: A voxel-based meta-analysis
Authors: Yang Xun , Hu Liyuan , Zeng Jianguang , Tan Ying , Cheng Bochao
Published: October 2016

Specific frontolimbic abnormalities are hypothesized to underlie the etiology of borderline personality disorder (BPD). However, findings from neuroimaging studies were inconsistent. In the current study, we aimed to provide a complete overview of cerebral microstructural alterations in gray matter (GM) of BPD patients. A total of 11 studies were enrolled, comprising 275 BPD patients and 290 healthy controls (HCs). A meta-analysis was conduct to quantitatively estimate regional GM abnormalities in BPD patients using the seed-based d mapping (SDM). Meta-regression was also conducted. Compared with HCs, the BPD patients exhibited increased GM mainly in bilateral supplementary motor area extending to right posterior cingulated cortex (PCC) and bilateral primary motor cortex, right middle frontal gyrus (MFG), and the bilateral precuneus extending to bilateral PCC. Decreased GM was identified in bilateral middle temporal gyri, right inferior frontal gyrus extending to right insular, left hippocampus and left superior frontal gyrus extending to left medial orbitofrontal cortex. The mean age of BPD patients were found nagativly associated with GM alterations in right MFG. Our findings suggested that BPD patients have significantly GM abnormalities in the default mode network and frontolimbic circuit. Our results provided further evidences in elucidating the underline neural mechanisms of BPD.
Correlation of serum hepcidin levels with disease progression in hepatitis B virus-related disease assessed by nanopore film based assay
Authors: Wang Jing , Dong Ailian , Liu Gang , Anderson Gregory J. , Hu Tony Y. , Shi Jian , Hu Yulin , Nie Guangjun
Published: October 2016

Chronic hepatitis B virus (HBV) infection often develop into cirrhosis, and both are major risk factors of hepatocellular carcinoma. However, effective approaches for the monitoring of HBV-related disease progress are still in need. Increased iron storage has an important role in HBV-related diseases. Hepcidin is a key regulator of iron homeostasis whose expression changes are often indicative of abnormal iron metabolism. There are few reports of hepcidin levels in patients with HBV infections, and the available results are inconsistent. In this study, using a recently validated nanopore silica film based method, we measured serum hepcidin levels in 46 HBV-related patients and 20 healthy controls. Patients were divided into three groups: chronic hepatitis B without cirrhosis; HBV-related cirrhosis; and HBV-related cirrhosis with hepatocellular carcinoma. Compared to healthy controls, the mean serum hepcidin level was significantly higher in CHB patients without cirrhosis, and in those with hepatocellular carcinoma, but not in those with cirrhosis. Iron-loading, viral infection and liver dysfunction are determined to be the major regulators of hepcidin in these patients. These observations suggest correlations between serum hepcidin and progression of chronic HBV infection, and may shed a new light on the development of biomarkers for HBV-related disease surveillance.
Investigating enhanced mechanical properties in dual-phase Fe-Ga-Tb alloys
Authors: Meng Chongzheng , Wang Hui , Wu Yuye , Liu Jinghua , Jiang Chengbao
Published: October 2016

Dual-phase (Fe83Ga17)100−xTbx alloys with 0 ≤ x ≤ 1 were synthesized by arc melting and homogenization treatment. The microstructures and the corresponding mechanical properties were systematically investigated. The chemical composition of the body centered cubic matrix is Fe83Ga17. The monoclinic second phase was composed of meltable precipitates with approximate composition Fe57Ga33Tb10. The nano-hardness of matrix and precipitates were 2.55 ± 0.17 GPa and 6.81 ± 1.03 GPa, respectively. Both the ultimate tensile strength (UTS) and fracture strain (ε) of the alloys were improved by the precipitates for x ≤ 0.2 alloys, but the strain decreases significantly at higher values of x. As potential structural-functional materials, the best mechanical properties obtained were a UTS of 595 ± 10 MPa and an ε of 3.5 ± 0.1%, four-fold and seven-fold improvements compared with the un-doped alloy. The mechanism for these anomalous changes of mechanical properties was attributed to the dispersed precipitates and semi-coherent interfaces, which serve as strong obstacles to dislocation motion and reduce the stress concentration at the grain boundaries. A sizeable improvement of magnetostriction induced by the precipitates in the range 0 ≤ x ≤ 0.2 was discovered and an optimal value of 150 ± 5 ppm is found, over three times higher than that of the un-doped alloy.
Soybean GmDREBL Increases Lipid Content in Seeds of Transgenic Arabidopsis
Authors: Zhang Yu-Qin , Lu Xiang , Zhao Fei-Yi , Li Qing-Tian , Niu Su-Ling , Wei Wei , Zhang Wan-Ke , Ma Biao , Chen Shou-Yi , Zhang Jin-Song
Published: October 2016

A DREB-type transcription factor gene GmDREBL has been characterized for its functions in oil accumulation in seeds. The gene is specifically expressed in soybean seeds. The GmDREBL is localized in nucleus and has transcriptional activation ability. Overexpression of GmDREBL increased the fatty acid content in the seeds of transgenic Arabidopsis plants. GmDREBL can bind to the promoter region of WRI1 to activate its expression. Several other genes in the fatty acid biosynthesis pathway were also enhanced in the GmDREBL-transgenic plants. The GmDREBL can be up-regulated by GmABI3 and GmABI5. Additionally, overexpression of GmDREBL significantly promoted seed size in transgenic plants compared to that of WT plants. Expression of the DREBL is at higher level on the average in cultivated soybeans than that in wild soybeans. The promoter of the DREBL may have been subjected to selection during soybean domestication. Our results demonstrate that GmDREBL participates in the regulation of fatty acid accumulation by controlling the expression of WRI1 and its downstream genes and manipulation of the gene may increase the oil contents in soybean plants. Our study provides novel insights into the function of DREB-type transcription factors in oil accumulation in addition to their roles in stress response.
A vector platform for the rapid and efficient engineering of stable complex transgenes
Authors: Jäckel Carsten , Nogueira Melanie Schmitt , Ehni Nadja , Kraus Christiane , Ranke Julius , Dohmann Maike , Noessner Elfriede , Nelson Peter J.
Published: October 2016

We describe the generation of a set of plasmid vector tools that allow the rapid generation of complex-interacting stable transgenes in immortalized and primary cells. Of particular importance is inclusion of a mechanism to monitor the activation status of regulatory pathways via a reporter cassette (using Gaussia Luciferase), with control of additional transgene expression through doxycycline de-repression. The resulting vectors can be used to assess regulatory pathway activation and are well suited for regulatory pathway crosstalk studies. The system incorporates MultiSite-Gateway cloning for the rapid generation of vectors allowing flexible choice of promoters and transgenes and Sleeping Beauty transposase technology for efficient incorporation of multiple transgenes in into host cell DNA. The vectors and a library of compatible Gateway Entry clones are available from the non-profit plasmid repository Addgene.
Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models
Authors: Li Yi-Fang , Chang Yi-Qun , Deng Jie , Li Wei-Xi , Jian Jie , Gao Jia-Suo , Wan Xin , Gao Hao , Kurihara Hiroshi , Sun Ping-Hua , He Rong-Rong
Published: October 2016

The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2′R,3′R)-desgalloyloolongtheanin-3,3′-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 μg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.
Inhibition of Rac1 GTPase activity affects porcine oocyte maturation and early embryo development
Authors: Song Si-Jing , Wang Qiao-Chu , Jia Ru-Xia , Cui Xiang-Shun , Kim Nam-Hyung , Sun Shao-Chen
Published: October 2016

Mammalian oocyte asymmetric division relies on the eccentric positioning of the spindle, resulting in the polar body formation. Small signaling G protein Rac1 is a member of GTPases, which regulates a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. However, effects of Rac1 on the porcine oocyte maturation and early embryo development are not fully understood. In present study we investigated the role of Rac1 in oocyte maturation and embryo cleavage. We first found that Rac1 localized at the cortex of the porcine oocytes, and disrupting the Rac1 activities by treating with NSC 23766 led to the failure of polar body emission. In addition, a majority of treated oocytes exhibited abnormal spindle morphology, indicating that Rac1 may involve into porcine oocyte spindle formation. This might be due to the regulation of Rac1 on MAPK, since p-MAPK expression decreased after NSC 23766 treatments. Moreover, we found that the position of most meiotic spindles in treated oocytes were away from the cortex, indicating the roles of Rac1 on meiotic spindle positioning. Our results also showed that inhibition of Rac1 activity caused the failure of early embryo development. Therefore, our study showed the critical roles of Rac1 GTPase on porcine oocyte maturation and early embryo cleavage.
Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI
Authors: Pfeiler Susanne , Khandagale Avinash B. , Magenau Astrid , Nichols Maryana , Heijnen Harry F. G. , Rinninger Franz , Ziegler Tilman , Seveau Stephanie , Schubert Sören , Zahler Stefan , Verschoor Admar , Latz Eicke , Massberg Steffen , Gaus Katharina , Engelmann Bernd
Published: October 2016

The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of Ly6C+ (inflammatory) macrophages and prevented hepatocyte necrosis in the core of infectious foci. Perifocal levels of Ly6C+ macrophages and Ly6C− macrophages were unaffected, indicating predominant regulation of the focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune cells and dead bacteria but barely influenced bacterial sequestration and survival or inflammasome activation, thus exclusively counteracting damage inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance pathway that partially responds to products of antimicrobial defenses and selectively prevents immunity-induced damage during acute infection. Our findings suggest that control of infection-associated immunopathology can be based on a unified defense operation.
A capillary electrophoresis coupled to mass spectrometry pipeline for long term comparable assessment of the urinary metabolome
Authors: Boizard Franck , Brunchault Valérie , Moulos Panagiotis , Breuil Benjamin , Klein Julie , Lounis Nadia , Caubet Cécile , Tellier Stéphanie , Bascands Jean-Loup , Decramer Stéphane , Schanstra Joost P. , Buffin-Meyer Bénédicte
Published: October 2016

Although capillary electrophoresis coupled to mass spectrometry (CE-MS) has potential application in the field of metabolite profiling, very few studies actually used CE-MS to identify clinically useful body fluid metabolites. Here we present an optimized CE-MS setup and analysis pipeline to reproducibly explore the metabolite content of urine. We show that the use of a beveled tip capillary improves the sensitivity of detection over a flat tip. We also present a novel normalization procedure based on the use of endogenous stable urinary metabolites identified in the combined metabolome of 75 different urine samples from healthy and diseased individuals. This method allows a highly reproducible comparison of the same sample analyzed nearly 130 times over a range of 4 years. To demonstrate the use of this pipeline in clinical research we compared the urinary metabolome of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy newborns. We identified 32 features with differential urinary abundance. Combination of the 32 compounds in a SVM classifier predicted with 76% sensitivity and 86% specificity UPJ obstruction in a separate validation cohort of 24 individuals. Thus, this study demonstrates the feasibility to use CE-MS as a tool for the identification of clinically relevant urinary metabolites.
Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection
Authors: Hu Rong , Chen Juan , Lujan Brendan , Lei Ruixue , Zhang Mi , Wang Zefen , Liao Mingxia , Li Zhiqiang , Wan Yu , Liu Fang , Feng Hua , Wan Qi
Published: October 2016

Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The effect of glycine on Akt activation is sensitive to the antagonist of glycine-GluN1 binding site. As a functional consequence, glycine protects against excitotoxicity-induced neuronal death through the non-ionotropic activity of GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus, this study reveals an unexpected role of glycine in eliciting a non-ionotropic activity of GluN2ARs to confer neuroprotection via Akt activation.
Efficient long-term cryopreservation of pluripotent stem cells at −80 °C
Authors: Yuan Ye , Yang Ying , Tian Yuchen , Park Jinkyu , Dai Aihua , Roberts R. Michael , Liu Yang , Han Xu
Published: October 2016

Current long term cryopreservation of cell stocks routinely requires the use of liquid nitrogen (LN2), because commonly used cryopreservation media containing cell membrane permeating cryoprotectants are thermally unstable when frozen at higher storage temperatures, e.g. −80 °C. This instability leads to ice recrystallization, causing progressive loss of cell viability over time under the storage conditions provided by most laboratory deep freezers. The dependency on LN2for cell storage significantly increases operational expense and raises issues related to impaired working efficiency and safety. Here we demonstrate that addition of Ficoll 70 to cryoprotectant solutions significantly improves system thermal stability at the working temperature (~−80 °C) of laboratory deep freezers. Moreover, a medium comprised of Ficoll 70 and dimethyl sulfoxide (DMSO) in presence or absence of fetal bovine serum (FBS) can provide reliable cryopreservation of various kinds of human and porcine pluripotent stem cells at −80 °C for periods that extend up to at least one year, with the post-thaw viability, plating efficiency, and full retention of pluripotent phenotype comparable to that achieved with LN2storage. These results illustrate the practicability of a promising long-term cryopreservation method that completely eliminates the need for LN2.
A proteinaceous organic matrix regulates carbonate mineral production in the marine teleost intestine
Authors: Schauer Kevin L. , LeMoine Christophe M. R. , Pelin Adrian , Corradi Nicolas , McDonald M. Danielle , Warren Wesley C. , Grosell Martin
Published: October 2016

Marine teleost fish produce CaCO3in their intestine as part of their osmoregulatory strategy. This precipitation is critical for rehydration and survival of the largest vertebrate group on earth, yet the molecular mechanisms that regulate this reaction are unknown. Here, we isolate and characterize an organic matrix associated with the intestinal precipitates produced by Gulf toadfish (Opsanus beta). Toadfish precipitates were purified using two different methods, and the associated organic matrix was extracted. Greater than 150 proteins were identified in the isolated matrix by mass spectrometry and subsequent database searching using anO. betatranscriptomic sequence library produced here. Many of the identified proteins were enriched in the matrix compared to the intestinal fluid, and three showed no substantial homology to any previously characterized protein in the NCBI database. To test the functionality of the isolated matrix, a micro-modifiedin vitrocalcification assay was designed, which revealed that low concentrations of isolated matrix substantially promoted CaCO3production, where high concentrations showed an inhibitory effect. High concentrations of matrix also decreased the incorporation of magnesium into the forming mineral, potentially providing an explanation for the variability in magnesium content observed in precipitates produced by different fish species.