bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Time of Day of Application of 2,4-D, Dicamba, Glufosinate, Paraquat, and Saflufenacil on Horseweed (Conyza canadensis) Control
Authors: Montgomery Garret B. , Treadway Joyce A. , Reeves Julie L. , Steckel Lawrence E.
Published: August 2017

A study to evaluate the effect of application time of day (TOD) on the efficacy of five burndown herbicides was conducted in Alabama and Tennessee. Treatments of 2,4-D, dicamba, glufosinate, paraquat, and saflufenacil were applied at sunrise, midday, or sunset to a native population of horseweed and analyzed separately. Control of glyphosate-resistant (GR) horseweed with 2,4-D, dicamba, glufosinate, and saflufenacil was greatest from the midday application. Percentage of living horseweed counts for all of these herbicides followed a similar pattern. Control from paraquat was lowest at the midday timing and greatest from the sunset application with surviving horseweed plant populations reflecting those control ratings. Application TOD significantly affected all of the herbicides in this research. Applications of 2,4-D, dicamba, glufosinate, and saflufenacil are more efficacious when applied during the middle portion of the day, while paraquat is more efficacious when applied at sunset for maximum horseweed control.
Limpograss (Hemarthria altissima) Tolerance to Hexazinone
Authors: Lastinger Cody A. , Dias José Luiz C. S. , Sellers Brent A. , Ferrell Jason A. , Silveira Maria L. , Vendramini João M. B.
Published: August 2017

Field trials were conducted in 2013 and 2014 to investigate the tolerance of limpograss to increasing rates of hexazinone. Dose-response curves were generated using linear and quadratic regression models to determine the hexazinone estimated dose (ED) required to provide 10% (ED10) and 20% (ED20) of visual injury and herbage mass reduction. The ED10and ED20for visual estimates of injury were estimated to be 0.05 and 0.14 kg ai ha-1at 60 d after treatment (DAT). Regarding forage herbage mass reduction, the ED10and ED20were estimated to be 0.07 and 0.19 kg ai ha-1in 2013, whereas in 2014, the ED10and ED20were estimated to be 0.03 and 0.06 kg ai ha-1, respectively. The significant difference in herbage mass reduction between 2013 and 2014 was likely due to rainfall patterns, which possibly promoted hexazinone leaching in 2013 and consequently, less activity. Overall, hexazinone resulted in high degrees of limpograss injury across all response variables in both years; therefore, smutgrass control in limpograss pastures with hexazinone may not be a viable option. The presence or absence of smutgrass should be considered before limpograss establishment as there is no viable herbicide to selectively remove smutgrass from limpograss swards.
Photoelectrochemical oxidation of organic substrates in organic media
Authors: Li Tengfei , Kasahara Takahito , He Jingfu , Dettelbach Kevan E. , Sammis Glenn M. , Berlinguette Curtis P.
Published: August 2017

There is a global effort to convert sunlight into fuels by photoelectrochemically splitting water to form hydrogen fuels, but the dioxygen byproduct bears little economic value. This raises the important question of whether higher value commodities can be produced instead of dioxygen. We report here photoelectrochemistry at a BiVO4 photoanode involving the oxidation of substrates in organic media. The use of MeCN instead of water enables a broader set of chemical transformations to be performed (e.g., alcohol oxidation and C-H activation/oxidation), while suppressing photocorrosion of BiVO4 that otherwise occurs readily in water, and sunlight reduces the electrical energy required to drive organic transformations by 60%. These collective results demonstrate the utility of using photoelectrochemical cells to mediate organic transformations that otherwise require expensive and toxic reagents or catalysts.
Transport and excitations in a negative-U quantum dot at the LaAlO3/SrTiO3 interface
Authors: Prawiroatmodjo Guenevere E. D. K. , Leijnse Martin , Trier Felix , Chen Yunzhong , Christensen Dennis V. , von Soosten Merlin , Pryds Nini , Jespersen Thomas S.
Published: August 2017

In a solid-state host, attractive electron–electron interactions can lead to the formation of local electron pairs which play an important role in the understanding of prominent phenomena such as high Tc superconductivity and the pseudogap phase. Recently, evidence of a paired ground state without superconductivity was demonstrated at the level of single electrons in quantum dots at the interface of LaAlO3 and SrTiO3. Here, we present a detailed study of the excitation spectrum and transport processes of a gate-defined LaAlO3/SrTiO3 quantum dot exhibiting pairing at low temperatures. For weak tunneling, the spectrum agrees with calculations based on the Anderson model with a negative effective charging energy U, and exhibits an energy gap corresponding to the Zeeman energy of the magnetic pair-breaking field. In contrast, for strong coupling, low-bias conductance is enhanced with a characteristic dependence on temperature, magnetic field and chemical potential consistent with the charge Kondo effect.
Colossal permittivity behavior and its origin in rutile (Mg1/3Ta2/3)xTi1-xO2
Authors: Dong Wen , Chen Dehong , Hu Wanbiao , Frankcombe Terry J. , Chen Hua , Zhou Chao , Fu Zhenxiao , Wei Xiaoyong , Xu Zhuo , Liu Zhifu , Li Yongxiang , Liu Yun
Published: August 2017

This work investigates the synthesis, chemical composition, defect structures and associated dielectric properties of (Mg2+, Ta5+) co-doped rutile TiO2 polycrystalline ceramics with nominal compositions of (Mg2+1/3Ta5+2/3)
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defect clusters with a specific configuration, different from the defect cluster form previously reported in tri-/pent-valent ion co-doped rutile TiO2. This work extends the research on colossal permittivity and defect formation to bi-/penta-valent ion co-doped rutile TiO2 and elucidates a likely defect cluster model for this system. We therefore believe these results will benefit further development of colossal permittivity materials and advance the understanding of defect chemistry in solids.
Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3Kδ/Akt and NFκB induction in a murine asthma model
Authors: El-Hashim Ahmed Z. , Khajah Maitham A. , Renno Waleed M. , Babyson Rhema S. , Uddin Mohib , Benter Ibrahim F. , Ezeamuzie Charles , Akhtar Saghir
Published: August 2017

The molecular mechanisms underlying asthma pathogenesis are poorly characterized. In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kδ/Akt and NF-κB are signaling effectors downstream of Src/EGFR activation; and (3) if upstream inhibition of Src/EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways. Allergic inflammation resulted in increased phosphorylation of EGFR, Akt, ERK1/2 and IκB in the lung tissues from ovalbumin (OVA)-challenged BALB/c mice. Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness. Treatment with pathway-selective inhibitors for ERK1/2 (PD89059) and PI3Kδ/Akt (IC-87114) respectively, or an inhibitor of NF-κB (BAY11-7085) also reduced the OVA-induced asthmatic phenotype but to a lesser extent compared to Src/EGFR inhibition. Thus, Src via EGFR transactivation and subsequent downstream activation of multiple pathways regulates the allergic airway inflammatory response. Furthermore, a broader upstream inhibition of Src/EGFR offers an attractive therapeutic alternative in the treatment of asthma relative to selectively targeting the individual downstream signaling effectors.
Evaluation of the condyle remodeling after lateral arthroplasty in growing children with temporomandibular joint ankylosis
Authors: Yang XiuJuan , Lu Chuan , Dong MinJun , He DongMei , Yang Chi , Hu YiHui
Published: August 2017

Temporomandibular joint (TMJ) ankylosis in growing patients can cause both mouth opening limitation and jaw bone deformity. Lateral arthroplasty (LAP) can restore the medially displaced condyle and thus keep its growth potential. But can the condyle grow as normal is unknown. This study was to evaluate the long-term result after LAP in growing children. Patients from 2010 to 2014 were evaluated. Their CT data within 1 week after operation and during at least 1-year follow-ups were measured by ProPlan CMF 1.4 software. The condyle-ramus length of both sides and angles and the chin deviation before and after operation were compared. SPSS 17.0 software was used for statistical analysis. A total of 9 patients with a mean age of 10.2 years were included in the study. The mean follow-up period was 1.94 years. The mean condyle-ramus growth was 2.90 mm in the affected side and 2.50 mm in the unaffected side (P = 0.31). All of the affected side exhibited growth and remodeling of the condyle and ramus. All 9 cases had a mean chin deviation of 3.69 mm before operation and 2.92 mm during follow-ups (P = 0.16). The residual condyle grows after LAP, which can reduce the gravity of jawbone deformity.
Electrically Tunable Metamaterials Based on Multimaterial Nanowires Incorporating Transparent Conductive Oxides
Authors: Salary Mohammad Mahdi , Mosallaei Hossein
Published: August 2017

We present novel design approaches for metasurfaces and metamaterials with electrical tunability offering real-time manipulation of light and serving as multifunctional devices in near-infrared frequency regime (at the specific wavelength of 1.55 μm). For this purpose, we integrate indium-tin-oxide (ITO) as a tunable electro-optical material into multimaterial nanowires with metal-oxide-semiconductor and metal-insulator-metal configurations. In particular, an active metasurface operating in the transmission mode is designed which allows for modulation of the transmitted light phase over 280 degrees. This large phase modulation is afforded in the cost of low transmission efficiency. We demonstrate the use of such active metasurfaces for tunable bending and focusing in free-space. Moreover, we investigate the implementation of this material in deeply subwavelength multimaterial nanowires, which can yield strong variations in the effective refractive index by the virtue of internal homogenization enabling tunability of the performance in gradient refractive index metamaterials. In the theoretical modeling of these structures, we adopt a hierarchical multiscale approach by linking drift-diffusion transport model with the electromagnetic model which rigorously characterizes the electro-optical effects.
Visible light high-resolution imaging system for large aperture telescope by liquid crystal adaptive optics with phase diversity technique
Authors: Xu Zihao , Yang Chengliang , Zhang Peiguang , Zhang Xingyun , Cao Zhaoliang , Mu Quanquan , Sun Qiang , Xuan Li
Published: August 2017

There are more than eight large aperture telescopes (larger than eight meters) equipped with adaptive optics system in the world until now. Due to the limitations such as the difficulties of increasing actuator number of deformable mirror, most of them work in the infrared waveband. A novel two-step high-resolution optical imaging approach is proposed by applying phase diversity (PD) technique to the open-loop liquid crystal adaptive optics system (LC AOS) for visible light high-resolution adaptive imaging. Considering the traditional PD is not suitable for LC AOS, the novel PD strategy is proposed which can reduce the wavefront estimating error caused by non-modulated light generated by liquid crystal spatial light modulator (LC SLM) and make the residual distortions after open-loop correction to be smaller. Moreover, the LC SLM can introduce any aberration which realizes the free selection of phase diversity. The estimating errors are greatly reduced in both simulations and experiments. The resolution of the reconstructed image is greatly improved on both subjective visual effect and the highest discernible space resolution. Such technique can be widely used in large aperture telescopes for astronomical observations such as terrestrial planets, quasars and also can be used in other applications related to wavefront correction.
Activation of NADPH oxidases leads to DNA damage in esophageal cells
Authors: Bhardwaj Vikas , Gokulan Ravindran Caspa , Horvat Andela , Yermalitskaya Liudmila , Korolkova Olga , Washington Kay M. , El-Rifai Wael , Dikalov Sergey I. , Zaika Alexander I.
Published: August 2017

Gastroesophageal reflux disease (GERD) is the strongest known risk factor for esophageal adenocarcinoma. In the center of tumorigenic events caused by GERD is repeated damage of esophageal tissues by the refluxate. In this study, we focused on a genotoxic aspect of exposure of esophageal cells to acidic bile reflux (BA/A). Analyzing cells generated from patients with Barrett’s esophagus and human esophageal specimens, we found that BA/A cause significant DNA damage that is mediated by reactive-oxygen species. ROS originate from mitochondria and NADPH oxidases. We specifically identified NOX1 and NOX2 enzymes to be responsible for ROS generation. Inhibition of NOX2 and NOX1 with siRNA or chemical inhibitors significantly suppresses ROS production and DNA damage induced by BA/A. Mechanistically, our data showed that exposure of esophageal cells to acidic bile salts induces phosphorylation of the p47phox subunit of NOX2 and its translocation to the cellular membrane. This process is mediated by protein kinase C, which is activated by BA/A. Taken together, our studies suggest that inhibition of ROS induced by reflux can be a useful strategy for preventing DNA damage and decreasing the risk of tumorigenic transformation caused by GERD.
Properties of residual titanium dioxide nanoparticles after extended periods of mixing and settling in synthetic and natural waters
Authors: Zhang Chunpeng , Lohwacharin Jenyuk , Takizawa Satoshi
Published: August 2017

Titanium dioxide nanoparticle (TiO2 NP) discharged into water bodies can affect ecosystems and human health adversely. We studied the properties of residual TiO2 NPs with and without gentle mixing (to simulate a natural environment more closely) and after settling for 12-h periods. Surface complexation, dynamic particle size changes, and TiO2 NP destabilization in synthetic and lake waters were investigated. The accumulation of inert ions (Na+ and Cl−) in the diffuse layer which was not discussed in other studies was supposed to be the main reason that aggregation occurred slowly and continuously. PO43− stabilized and destabilized TiO2 NPs at 10 mM and 100 mM, respectively. Destabilization occurred because high ionic strength overwhelmed increased negative charges of TiO2 NPs by complexation with PO43−. TiO2 NP destabilization was achieved in approximately 12 h in synthetic and lake waters, and is attributed to the slow diffusion of ions into aggregates. Despite the presence of moderately high concentrations of natural organic matter, which tends to stabilize TiO2 NPs, the addition of 20 mM PO43− destabilized the TiO2 NPs in lake water. Smaller aggregate sizes formed compared with those before destabilization, which indicates that stable residual TiO2 NPs could exist in aquatic environments after extended periods.
Whey Protein Components - Lactalbumin and Lactoferrin - Improve Energy Balance and Metabolism
Authors: Zapata Rizaldy C. , Singh Arashdeep , Pezeshki Adel , Nibber Traj , Chelikani Prasanth K.
Published: August 2017

Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of β-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.
Toxic fluoride gas emissions from lithium-ion battery fires
Authors: Larsson Fredrik , Andersson Petra , Blomqvist Per , Mellander Bengt-Erik
Published: August 2017

Lithium-ion battery fires generate intense heat and considerable amounts of gas and smoke. Although the emission of toxic gases can be a larger threat than the heat, the knowledge of such emissions is limited. This paper presents quantitative measurements of heat release and fluoride gas emissions during battery fires for seven different types of commercial lithium-ion batteries. The results have been validated using two independent measurement techniques and show that large amounts of hydrogen fluoride (HF) may be generated, ranging between 20 and 200 mg/Wh of nominal battery energy capacity. In addition, 15–22 mg/Wh of another potentially toxic gas, phosphoryl fluoride (POF3), was measured in some of the fire tests. Gas emissions when using water mist as extinguishing agent were also investigated. Fluoride gas emission can pose a serious toxic threat and the results are crucial findings for risk assessment and management, especially for large Li-ion battery packs.
No evidence for parental age effects on offspring leukocyte telomere length in free-living Soay sheep
Authors: Froy H. , Bird E. J. , Wilbourn R. V. , Fairlie J. , Underwood S. L. , Salvo-Chirnside E. , Pilkington J. G. , Bérénos C. , Pemberton J. M. , Nussey D. H.
Published: August 2017

In humans, the effect of paternal age at conception (PAC) on offspring leukocyte telomere length (LTL) is well established, with older fathers thought to pass on longer telomeres to their offspring in their sperm. Few studies have looked for PAC effects in other species, but it has been hypothesised that the effect will be exacerbated in polygamous species with higher levels of sperm competition and production. We test for maternal (MAC) and paternal age at conception effects on offspring LTL in Soay sheep, a primitive breed experiencing strong sperm competition. We use qPCR to measure relative telomere length in 389 blood samples (n = 318 individuals) collected from an unmanaged population of sheep on St Kilda, where individual age and parentage are known. We find no evidence that either MAC or PAC are associated with LTL in offspring across the age range, or when considering only young lambs (n = 164). This is the first study to test for parental age effects on offspring LTL in a wild mammal population, and the results contrast with the findings of numerous human studies that find a PAC effect, as well as predictions of a stronger PAC effect in polygamous species.
A signal-based method for finding driver modules of breast cancer metastasis to the lung
Authors: Yan Gaibo , Chen Vicky , Lu Xinghua , Lu Songjian
Published: August 2017

Tumor metastasis is mainly caused by somatic genomic alterations (SGAs) that perturb pathways regulating metastasis-relevant activities and thus help the primary tumor to adapt to the new microenvironment. Identifying drivers of metastasis, i.e. SGAs, sheds light on the metastasis mechanism and provides guidance for targeted therapy. In this paper, we introduce a novel method to search for SGAs driving breast cancer metastasis to the lung. First, we search for transcriptomic modules with genes that are differentially expressed in breast cell lines with strong metastatic activities to the lung and co-expressed in a large number of breast tumors. Then, for each transcriptomic module, we search for a set of SGA genes (driver modules) such that genes in each driver module carry a common signal regulating the transcriptomic module. Evaluations indicate that many genes in driver modules are indeed related to metastasis, and our methods have identified many new driver candidates. We further choose two novel metastatic driver genes,BCL2L11andCDH9, forin vitroverification. The wound healing assay reveals that inhibiting eitherBCL2L11orCDH9will enhance the migration of cell lines, which provides evidence that these two genes are suppressors of tumor metastasis.
Plasma biomarker proteins for detection of human growth hormone administration in athletes
Authors: Tan Sock-Hwee , Lee Albert , Pascovici Dana , Care Natasha , Birzniece Vita , Ho Ken , Molloy Mark P. , Khan Alamgir
Published: August 2017

Human growth hormone (GH) is a naturally occurring hormone secreted by the pituitary gland with anabolic and growth-promoting activities. Since an increased availability of recombinant GH (rGH) for the treatment of GH-deficient patients, GH has been abused in sports and it is prohibited. “GH-isoform” and “biomarkers” tests are currently available for detection of GH abuse in sports, however both methods suffer from shortcomings. Here, we report on a proteomic approach to search for novel protein biomarkers associated with rGH administration in non-elite athletes. In this study, participants received either placebo or rGH for 8 weeks, and were followed over a 6-week washout period. We used 2-D DIGE and iTRAQ LC-MS/MS analyses to expose rGH-dependent marker proteins. Eight rGH-dependent plasma proteins namely apolipoproptein-L1, alpha-HS-glycoprotein, vitamin D-binding protein, afamin, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-ALS, lumican and extracellular matrix proteins 1 were identified. Apolipoprotein L1 and alpha-HS-glycoprotein were validated by Western blots to confirm their identities and expression patterns in rGH- and placebo-treated subject cohorts. Independent confirmation of these putative GH-responsive biomarkers would be of value for clinical practices and may have sports anti-doping utility.
Genome-wide genetic structure and differentially selected regions among Landrace, Erhualian, and Meishan pigs using specific-locus amplified fragment sequencing
Authors: Li Zhen , Wei Shengjuan , Li Hejun , Wu Keliang , Cai Zhaowei , Li Dongfeng , Wei Wei , Li Qifa , Chen Jie , Liu Honglin , Zhang Lifan
Published: August 2017

As typical Chinese indigenous pig breeds, Erhualian and Meishan have been widely used to produce new strain or breed in the world. However, the genetic basis of characteristics of these pig breeds is still limited. Moreover, considering cost and output of sequencing, it is necessary to further develop cost-effective method for pig genome screening. To contribute on this issue, we developed a SLAF-seq (specific-locus amplified fragment sequencing) method for pigs and applied it to analyze the genetic difference among Landrace, Erhualian, and Meishan pigs. A total of 453.75 million reads were produced by SLAF-seq. After quality-control, 165,670 SNPs (single nucleotide polymorphisms) were used in further analysis. The results showed that Landrace had distinct genetic relationship compared to Erhualian (FST = 0.5480) and Meishan (FST = 0.5800), respectively, while Erhualian and Meishan held the relatively close genetic relationship (FST = 0.2335). Furthermore, a genome-wide scanning revealed 268 differentially selected regions (DSRs) with 855 genes and 256 DSRs with 347 genes between Landrace and the two Chinese indigenous pig breeds and between Erhualian and Meishan, respectively. This study provides a new cost-effective method for pig genome study and might contribute to a better understanding on the formation mechanism of genetic difference among pigs with different geographical origins.
Control of entanglement dynamics in a system of three coupled quantum oscillators
Authors: Gonzalez-Henao J. C. , Pugliese E. , Euzzor S. , Meucci R. , Roversi J. A. , Arecchi F. T.
Published: August 2017

Dynamical control of entanglement and its connection with the classical concept of instability is an intriguing matter which deserves accurate investigation for its important role in information processing, cryptography and quantum computing. Here we consider a tripartite quantum system made of three coupled quantum parametric oscillators in equilibrium with a common heat bath. The introduced parametrization consists of a pulse train with adjustable amplitude and duty cycle representing a more general case for the perturbation. From the experimental observation of the instability in the classical system we are able to predict the parameter values for which the entangled states exist. A different amount of entanglement and different onset times emerge when comparing two and three quantum oscillators. The system and the parametrization considered here open new perspectives for manipulating quantum features at high temperatures.
Diarrhea Morbidities in Small Areas: Accounting for Non-Stationarity in Sociodemographic Impacts using Bayesian Spatially Varying Coefficient Modelling
Authors: Osei F. B. , Stein A.
Published: August 2017

Model-based estimation of diarrhea risk and understanding the dependency on sociodemographic factors is important for prioritizing interventions. It is unsuitable to calibrate regression model with a single set of coefficients, especially for large spatial domains. For this purpose, we developed a Bayesian hierarchical varying coefficient model to account for non-stationarity in the covariates. We used the integrated nested Laplace approximation for parameter estimation. Diarrhea morbidities in Ghana motivated our empirical study. Results indicated improvement regarding model fit and epidemiological benefits. The findings highlighted substantial spatial, temporal, and spatio-temporal heterogeneities in both diarrhea risk and the coefficients of the sociodemographic factors. Diarrhea risk in peri-urban and urban districts were 13.2% and 10.8% higher than rural districts, respectively. The varying coefficient model indicated further details, as the coefficients varied across districts. A unit increase in the proportion of inhabitants with unsafe liquid waste disposal was found to increase diarrhea risk by 11.5%, with higher percentages within the south-central parts through to the south-western parts. Districts with safe and unsafe drinking water sources unexpectedly had a similar risk, as were districts with safe and unsafe toilets. The findings show that site-specific interventions need to consider the varying effects of sociodemographic factors.
Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process
Authors: Jing Yan , Jing Junjun , Ye Ling , Liu Xiaohua , Harris Stephen E. , Hinton Robert J. , Feng Jian Q.
Published: August 2017

Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiplein vivoapproaches to study the role ofBmpr1ain endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure whenBmpr1awas deleted usingAggrecan-CreERT2in early cartilage cells with a one-time tamoxifen injection. We observed the absence of lineage progression of chondrocyte-derived bone cells to form osteoblasts and osteocytes in metaphyses. Furthermore, we demonstrated the key contribution of growth plate chondrocytes and articular chondrocytes, not only for long bone growth, but also for bone remodeling. In contrast, deletingBmpr1ain early osteoblasts with3.6 Col 1-Crehad little impact on skeletal shape and size except for a sharp increase in osteoblasts and osteocytes, leading to a profound increase in bone volume. We conclude that chondrogenesis and osteogenesis are one continuous developmental and lineage-defined biological process, in whichBmpr1asignaling in chondrocytes is necessary for the formation of a pool or niche of osteoprogenitors that then contributes in a major way to overall bone formation and growth.
Studying the role of fascin-1 in mechanically stressed podocytes
Authors: Kliewe Felix , Scharf Christian , Rogge Henrik , Darm Katrin , Lindenmeyer Maja T. , Amann Kerstin , Cohen Clemens D. , Endlich Karlhans , Endlich Nicole
Published: August 2017

Glomerular hypertension causes glomerulosclerosis via the loss of podocytes, which are challenged by increased mechanical load. We have demonstrated that podocytes are mechanosensitive. However, the response of podocytes to mechanical stretching remains incompletely understood. Here we demonstrate that the actin-bundling protein fascin-1 plays an important role in podocytes that are exposed to mechanical stress. Immunofluorescence staining revealed colocalization of fascin-1 and nephrin in mouse kidney sections. In cultured mouse podocytes fascin-1 was localized along actin fibers and filopodia in stretched and unstretched podocytes. The mRNA and protein levels of fascin-1 were not affected by mechanical stress. By Western blot and 2D-gelelectrophoresis we observed that phospho-fascin-1 was significantly downregulated after mechanical stretching. It is known that phosphorylation at serine 39 (S39) regulates the bundling activity of fascin-1, e.g. required for filopodia formation. Podocytes expressing wild type GFP-fascin-1 and non-phosphorylatable GFP-fascin-1-S39A showed marked filopodia formation, being absent in podocytes expressing phosphomimetic GFP-fascin-1-S39D. Finally, the immunofluorescence signal of phosphorylated fascin-1 was strongly reduced in glomeruli of patients with diabetic nephropathy compared to healthy controls. In summary, mechanical stress dephosphorylates fascin-1 in podocytes in vitro and in vivo thereby fascin-1 may play an important role in the adaptation of podocytes to mechanical forces.
Functional non-coding polymorphism in an EPHA2 promoter PAX2 binding site modifies expression and alters the MAPK and AKT pathways
Authors: Ma Xiaoyin , Ma Zhiwei , Jiao Xiaodong , Hejtmancik J. Fielding
Published: August 2017

To identify possible genetic variants influencing expression of EPHA2 (Ephrin-receptor Type-A2), a tyrosine kinase receptor that has been shown to be important for lens development and to contribute to both congenital and age related cataract when mutated, the extended promoter region of EPHA2 was screened for variants. SNP rs6603883 lies in a PAX2 binding site in the EPHA2 promoter region. The C (minor) allele decreased EPHA2 transcriptional activity relative to the T allele by reducing the binding affinity of PAX2. Knockdown of PAX2 in human lens epithelial (HLE) cells decreased endogenous expression of EPHA2. Whole RNA sequencing showed that extracellular matrix (ECM), MAPK-AKT signaling pathways and cytoskeleton related genes were dysregulated in EPHA2 knockdown HLE cells. Taken together, these results indicate a functional non-coding SNP in EPHA2 promoter affects PAX2 binding and reduces EPHA2 expression. They further suggest that decreasing EPHA2 levels alters MAPK, AKT signaling pathways and ECM and cytoskeletal genes in lens cells that could contribute to cataract. These results demonstrate a direct role for PAX2 in EPHA2 expression and help delineate the role of EPHA2 in development and homeostasis required for lens transparency.
CD2068 potentially mediates multidrug efflux in Clostridium difficile
Authors: Ngernsombat Chawalit , Sreesai Suthasinee , Harnvoravongchai Phurt , Chankhamhaengdecha Surang , Janvilisri Tavan
Published: August 2017

Clostridium difficile is a major cause of antibiotic-associated diarrhea and the treatment thereof becomes more difficult owing to a rise of multidrug resistant strains. ATP-binding cassette (ABC) transporters are known to play a crucial role in the resistance to multiple antibiotics. In this study, the potential contribution of an ABC transporter in C. difficile multidrug resistance was investigated. The expression level of the cd2068 gene in C. difficile encoding an ABC transporter was up-regulated following the exposure to certain antibiotics compared to the control cells. Heterologous expression of CD2068 in Escherichia coli revealed that it mediated the efflux of fluorescent substrates and conferred resistance to multiple drugs. The CD2068-associated ATPase activity in membrane vesicles was also stimulated by various antibiotics. Furthermore, the insertional inactivation of the cd2068 gene in C. difficile led to a significant increase in susceptibility to antibiotics, which could be genetically complemented, supporting that CD2068 was directly associated to the drug resistance. These results demonstrate the potential role for the ABC transporter CD2068 in the resistance mechanism against multiple drugs in C. difficile.
New dating evidence of the early presence of hominins in Southern Europe
Authors: Michel Véronique , Shen Chuan-Chou , Woodhead Jon , Hu Hsun-Ming , Wu Chung-Che , Moullé Pierre-Élie , Khatib Samir , Cauche Dominique , Moncel Marie-Hélène , Valensi Patricia , Chou Yu-Min , Gallet Sylvain , Echassoux Anna , Orange François , de Lumley Henry
Published: August 2017

The first “Out of Africa” migrations represent a seminal event in the history of humankind. At the gates of Europe, the first appearance of Hominins is recorded in Georgia, 1.8 million years ago (Ma); however, the picture of migration across the continent remains incomplete. Vallonnet Cave (France) is a Lower Paleolithic prehistoric site with traces of hominin activities including lithic remains and cut-marks on mammal bones. Here, we apply the uranium-lead (U-Pb) methods to two flowstones to date the intervening archaeological levels. The U-Pb data, coupled with paleomagnetic constraints, provide an age range from 1.2 to 1.1 Ma. The results conclusively demonstrate that Vallonnet Cave is one of the oldest European prehistoric sites in France with early hominin occupations associated with an Epivillafranchian fauna. Combined with data from other archaeological sites, the new precise chronology suggests a widespread occupation the Northern Mediterranean to Southwestern Europe at ~1.2 Ma.
Library siRNA-generating RNA nanosponges for gene silencing by complementary rolling circle transcription
Authors: Han Sangwoo , Kim Hyejin , Lee Jong Bum
Published: August 2017

Since the discovery of RNA interference (RNAi), small interfering RNA (siRNA) has been powerful tools for gene downregulation in biomedical applications. Despite the outstanding efficacy of siRNA, the development of a therapeutic delivery system remains a challenge owing to the instability of RNA. In this study, we describe a new method for the design of siRNA-generating nanosponges by using complementary rolling circle transcription (cRCT), a technique that requires two complementary circular DNA. The sequences of one of the circular DNA are designed to have complete complementarity to the target mRNA resulting in double stranded RNA (dsRNA) that can be digested to siRNA by cellular Dicer activity. This siRNA design, called ‘library siRNA’, could be universally applied to fabricate RNA nanosponges targeting any known mRNA sequence.
In vivo immune interactions of multipotent stromal cells underlie their long-lasting pain-relieving effect
Authors: Guo Wei , Imai Satoshi , Yang Jia-Le , Zou Shiping , Watanabe Mineo , Chu Yu-Xia , Mohammad Zaid , Xu Huakun , Moudgil Kamal D. , Wei Feng , Dubner Ronald , Ren Ke
Published: August 2017

Systemic infusion of bone marrow stromal cells (BMSCs), a major type of multipotent stromal cells, produces pain relief (antihyperalgesia) that lasts for months. However, studies have shown that the majority of BMSCs are trapped in the lungs immediately after intravenous infusion and their survival time in the host is inconsistent with their lengthy antihyperalgesia. Here we show that long-lasting antihyperalgesia produced by BMSCs required their chemotactic factors such as CCL4 and CCR2, the integrations with the monocytes/macrophages population, and BMSC-induced monocyte CXCL1. The activation of central mu-opioid receptors related to CXCL1-CXCR2 signaling plays an important role in BMSC-produced antihyperalgesia. Our findings suggest that the maintenance of antihypergesia can be achieved by immune regulation without actual engraftment of BMSCs. In the capacity of therapeutic use of BMSCs other than structural repair and replacement, more attention should be directed to their role as immune modulators and subsequent alterations in the immune system.
Switching off hydrogen-bond-driven excitation modes in liquid methanol
Authors: Bellissima Stefano , González Miguel A. , Bafile Ubaldo , Cunsolo Alessandro , Formisano Ferdinando , De Panfilis Simone , Guarini Eleonora
Published: August 2017

Hydrogen bonding plays an essential role on intermolecular forces, and consequently on the thermodynamics of materials defined by this elusive bonding character. It determines the property of a vital liquid as water as well as many processes crucial for life. The longstanding controversy on the nature of the hydrogen bond (HB) can be settled by looking at the effect of a vanishing HB interaction on the microscopic properties of a given hydrogen-bonded fluid. This task suits the capabilities of computer simulations techniques, which allow to easily switch off HB interactions. We then use molecular dynamics to study the microscopic properties of methanol, a prototypical HB liquid. Fundamental aspects of the dynamics of methanol at room temperature were contextualised only very recently and its rich dynamics was found to have striking analogies with that of water. The lower temperature (200 K) considered in the present study led us to observe that the molecular centre-of-mass dynamics is dominated by four modes. Most importantly, the computational ability to switch on and off hydrogen bonds permitted us to identify which, among these modes, have a pure HB-origin. This clarifies the role of hydrogen bonds in liquid dynamics, disclosing new research opportunities and unexplored interpretation schemes.
Composition, diversity and bioactivity of culturable bacterial endophytes in mountain-cultivated ginseng in Korea
Authors: Khan Chowdhury MD. Emran , Jeon Junhyun , Ok Rim Soon , Park Young-Hwan , Kyu Lee Seung , Bae Hanhong
Published: August 2017

Plants harbor diverse communities of bacterial species in their internal compartments. Here we isolated and identified bacterial endophytes from mountain-cultivated ginseng (MCG, Panax ginseng Meyer) to make working collection of endophytes and exploit their potentially beneficial properties toward plants and human being. A total of 1,886 bacteria were isolated from root, stem and leaf of MCGs grown in 24 different sites across the nation, using culture-dependent approach. Sequencing of 16S rDNA allowed us to classify them into 252 distinct groups. Taxonomic binning of them resulted in 117 operational taxonomic units (OTUs). Analysis of diversity indices across sampling sites and tissues suggested that composition of bacterial endophyte community within ginseng could differ substantially from one site to the next as well as from one host compartment to another. Assessment of 252 bacterial isolates for their beneficial traits to host plants showed that some bacteria possesses the ability to promote plant growth and produce ß-glucosidase, indicating their potential roles in plant growth promotion and bio-transformation. Taken together, our work provides not only valuable resources for utilization of bacterial endophytes in ginseng but also insights into bacterial communities inside a plant of medicinal importance.
Non-equilibrium Inertial Separation Array for High-throughput, Large-volume Blood Fractionation
Authors: Mutlu Baris R. , Smith Kyle C. , Edd Jon F. , Nadar Priyanka , Dlamini Mcolisi , Kapur Ravi , Toner Mehmet
Published: August 2017

Microfluidic blood processing is used in a range of applications from cancer therapeutics to infectious disease diagnostics. As these applications are being translated to clinical use, processing larger volumes of blood in shorter timescales with high-reliability and robustness is becoming a pressing need. In this work, we report a scaled, label-free cell separation mechanism called non-equilibrium inertial separation array (NISA). The NISA mechanism consists of an array of islands that exert a passive inertial lift force on proximate cells, thus enabling gentler manipulation of the cells without the need of physical contact. As the cells follow their size-based, deterministic path to their equilibrium positions, a preset fraction of the flow is siphoned to separate the smaller cells from the main flow. The NISA device was used to fractionate 400 mL of whole blood in less than 3 hours, and produce an ultrapure buffy coat (96.6% white blood cell yield, 0.0059% red blood cell carryover) by processing whole blood at 3 mL/min, or ∼300 million cells/second. This device presents a feasible alternative for fractionating blood for transfusion, cellular therapy and blood-based diagnostics, and could significantly improve the sensitivity of rare cell isolation devices by increasing the processed whole blood volume.
Cognitive function during exercise under severe hypoxia
Authors: Komiyama Takaaki , Katayama Keisho , Sudo Mizuki , Ishida Koji , Higaki Yasuki , Ando Soichi
Published: August 2017

Acute exercise has been demonstrated to improve cognitive function. In contrast, severe hypoxia can impair cognitive function. Hence, cognitive function during exercise under severe hypoxia may be determined by the balance between the beneficial effects of exercise and the detrimental effects of severe hypoxia. However, the physiological factors that determine cognitive function during exercise under hypoxia remain unclear. Here, we examined the combined effects of acute exercise and severe hypoxia on cognitive function and identified physiological factors that determine cognitive function during exercise under severe hypoxia. The participants completed cognitive tasks at rest and during moderate exercise under either normoxic or severe hypoxic conditions. Peripheral oxygen saturation, cerebral oxygenation, and middle cerebral artery velocity were continuously monitored. Cerebral oxygen delivery was calculated as the product of estimated arterial oxygen content and cerebral blood flow. On average, cognitive performance improved during exercise under both normoxia and hypoxia, without sacrificing accuracy. However, under hypoxia, cognitive improvements were attenuated for individuals exhibiting a greater decrease in peripheral oxygen saturation. Cognitive performance was not associated with other physiological parameters. Taken together, the present results suggest that arterial desaturation attenuates cognitive improvements during exercise under hypoxia.
Estimating the epidemic risk using non-uniformly sampled contact data
Authors: Fournet Julie , Barrat Alain
Published: August 2017

Many datasets describing contacts in a population suffer from incompleteness due to population sampling and underreporting of contacts. Data-driven simulations of spreading processes using such incomplete data lead to an underestimation of the epidemic risk, and it is therefore important to devise methods to correct this bias. We focus here on a non-uniform sampling of the contacts between individuals, aimed at mimicking the results of diaries or surveys, and consider as case studies two datasets collected in different contexts. We show that using surrogate data built using a method developed in the case of uniform population sampling yields an improvement with respect to the use of the sampled data but is strongly limited by the underestimation of the link density in the sampled network. We put forward a second method to build surrogate data that assumes knowledge of the density of links within one of the groups forming the population. We show that it gives very good results when the population is strongly structured, and discuss its limitations in the case of a population with a weaker group structure. These limitations highlight the interest of measurements using wearable sensors able to yield accurate information on the structure and durations of contacts.
Highly efficient DNA-free gene disruption in the agricultural pest Ceratitis capitata by CRISPR-Cas9 ribonucleoprotein complexes
Authors: Meccariello Angela , Monti Simona Maria , Romanelli Alessandra , Colonna Rita , Primo Pasquale , Inghilterra Maria Grazia , Del Corsano Giuseppe , Ramaglia Antonio , Iazzetti Giovanni , Chiarore Antonia , Patti Francesco , Heinze Svenia D. , Salvemini Marco , Lindsay Helen , Chiavacci Elena , Burger Alexa , Robinson Mark D. , Mosimann Christian , Bopp Daniel , Saccone Giuseppe
Published: August 2017

The Mediterranean fruitflyCeratitis capitata(medfly) is an invasive agricultural pest of high economic impact and has become an emerging model for developing new genetic control strategies as an alternative to insecticides. Here, we report the successful adaptation of CRISPR-Cas9-based gene disruption in the medfly by injectingin vitropre-assembled, solubilized Cas9 ribonucleoprotein complexes (RNPs) loaded with gene-specific single guide RNAs (sgRNA) into early embryos. When targeting the eye pigmentation genewhite eye(we), a high rate of somatic mosaicism in surviving G0 adults was observed. Germline transmission rate of mutatedwealleles by G0 animals was on average above 52%, with individual cases achieving nearly 100%. We further recovered large deletions in thewegene when two sites were simultaneously targeted by two sgRNAs. CRISPR-Cas9 targeting of theCeratitisortholog of theDrosophilasegmentationpairedgene (Ccprd) caused segmental malformations in late embryos and in hatched larvae. Mutant phenotypes correlate with repair by non-homologous end-joining (NHEJ) lesions in the two targeted genes. This simple and highly effective Cas9 RNP-based gene editing to introduce mutations inC. capitatawill significantly advance the design and development of new effective strategies for pest control management.