bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoys provide a scalable platform for the identification of plant E3 ubiquitin ligases that regulate circadian function
Authors: Feke Ann , Liu Wei , Hong Jing , Li Man-Wah , Lee Chin-Mei , Zhou Elton K , Gendron Joshua M
Published: April 2019

The circadian clock relies on regulated degradation of clock proteins to maintain rhythmicity. Despite this, we know few components that mediate protein degradation. This is due to high levels of functional redundancy within plant E3 ubiquitin ligase families. In order to overcome this issue and discover E3 ubiquitin ligases that control circadian function, we generated a library of transgenic Arabidopsis plants expressing dominant-negative ‘decoy’ E3 ubiquitin ligases. We determined their effects on the circadian clock and identified dozens of new potential regulators of circadian function. To demonstrate the potency of the decoy screening methodology to overcome redundancy and identify bona fide clock regulators, we performed follow-up studies on MAC3A (PUB59) and MAC3B (PUB60). We show that they redundantly control circadian period by regulating splicing. This work demonstrates the viability of ubiquitin ligase decoys as a screening platform to overcome genetic challenges and discover E3 ubiquitin ligases that regulate plant development.
Text over time: The written word in English charm before 1350
Authors: Hindley Katherine
Published: April 2019

After the Norman Conquest, many of the charms that had circulated in Anglo-Saxon England disappeared from the written record, while new charming techniques emerged. Among the most striking changes was a sudden increase in the proportion of charms using written words. This paper explores this post-Conquest change in the use of charms by examining examples preserved in manuscripts written or owned in England from the Anglo-Saxon period to 1350. It begins by arguing that in Anglo-Saxon England different types of words were used to treat different kinds of illness or injury. Turning to the post-Conquest period, it identifies not only an increase in the proportionate use of written charms, but also emerging interest in the idea of textuality.
What to say while using dust from the Saints’ eyes? A Romanian case
Authors: Jiga Iliescu Laura
Published: April 2019

Hidden rituals are a category of religious practices, whose disclosure is not easy to be made by an outsider ethnologist. In this frame, a relatively less studied ensemble of gestures, which nowadays are almost perished, but whose traces are preserved in the Christian churches’ frescos from Orthodox space is represented by the act of voluntarily scratching the eyes of the saints painted on the wall. The paper systematizes the few references concerning this ritual entirety and also inquires about the relations established between the official dogma and the religious practices as actuated in the very case of the icon and the saint’s figure, in the 19th century Romanian milieu.
Enhancement of carbon monoxide concentration in atmosphere due to large scale forest fire of Uttarakhand
Authors: Thakur Jaya , Thever Prajesh , Gharai Biswadip , Sesha Sai MVR , Pamaraju VNRao
Published: April 2019

The richly forested Indian state of Uttarakhand experienced widespread forest fires in April to May 2016. The current study examines dispersion of carbon monoxide (CO) from the source regions of forest fire to distant places, using the Lagrangian particle dispersion model, FLEXPART. Atmospheric Infrared Sounder (AIRS) observations revealed that CO columnar concentrations had increased by almost 28 percentage during 24 April to 02 May 2016 with respect to the previous non-burning period of April 2016 at Uttarakhand. It is also seen that there is considerable enhancement of 45 percentage in average columnar concentration of CO during the burning period, compared to that in the previous 5 years as observed by AIRS. In the present study, concentrations of CO at different pressure levels and columnar CO over Uttarakhand during the forest fire event have been simulated using FLEXPART. The area averaged profile of model derived CO has been compared with the profile from AIRS onboard Aqua. Comparison between model derived columnar CO and satellite observations shows good agreement with coefficient of correlation (r) approximately 0.91 over the burnt areas. Further analysis using FLEXPART reveals that the transport of pollutants is towards north-eastern and eastern regions from the locations of forest fire events. Model derived vertical distribution of CO over Tibet, which is situated at the north-east of Uttarakhand, shows significant increase of CO concentration at higher altitudes around 3 km from the mean sea level during the fire event. FLEXPART results show that the emissions from the Uttarakhand fires were transported to Tibet during the study period.
The unfolding of iRFP713 in a crowded milieu
Authors: Stepanenko Olesya V. , Stepanenko Olga V. , Kuznetsova Irina M. , Turoverov Konstantin K.
Published: April 2019

The exploring of biological processes in vitro under conditions of macromolecular crowding is a way to achieve an understanding of how these processes occur in vivo. In this work, we study the unfolding of the fluorescent probe iRFP713 in crowded environment in vitro. Previously, we showed that the unfolding of the dimeric iRFP713 is accompanied by the formation of a compact monomer and an intermediate state of the protein. In the intermediate state, the macromolecules of iRFP713 have hydrophobic clusters exposed to the surface of the protein and are prone to aggregation. Concentrated solutions of polyethylene glycol (PEG-8000), Dextran-40 and Dextran-70 with a molecular mass of 8000, 40000 and 70000 Da, respectively, were used to model the conditions for macromolecular crowding. A limited available space provided by all the crowding agents used favors to the enhanced aggregation of iRFP713 in the intermediate state at the concentration of guanidine hydrochloride (GdnHCl), at which the charge of protein surface is neutralized by the guanidine cations. This is in line with the theory of the excluded volume. In concentrated solutions of the crowding agents (240–300 mg/ml), the stabilization of the structure of iRFP713 in the intermediate state is observed. PEG-8000 also enhances the stability of iRFP713 in the monomeric compact state, whereas in concentrated solutions of Dextran-40 and Dextran-70 the resistance of the protein in the monomeric state against GdnHCl-induced unfolding decreases. The obtained data argues for the excluded volume effect being not the only factor that contributes the behavior of biological molecules in a crowded milieu. Crowding agents do not affect the structure of the native dimer of iRFP713, which excludes the direct interactions between the target protein and the crowding agents. PEGs of different molecular mass and Dextran-40/Dextran-70 are known to influence the solvent properties of water. The solvent dipolarity/polarizability and basicity/acidity in aqueous solutions of these crowding agents vary in different ways. The change of the solvent properties in aqueous solutions of crowding agents might impact the functioning of a target protein.
Overexpression of lncRNA H19 changes basic characteristics and affects immune response of bovine mammary epithelial cells
Authors: Li Xuezhong , Wang Hao , Zhang Yanfen , Zhang Jinjing , Qi Shaopei , Zhang Yong , Gao Ming-Qing
Published: April 2019

The function of long non-coding RNA H19 (H19) on cell proliferation has been observed in various cell types, and the increased expression of H19 was also found in the lipopolysaccharide (LPS)-induced inflammatory bovine mammary epithelial cells (MAC-T). However, the roles of H19 in the inflammatory response and physiological functions of bovine mammary epithelial cell are not clear. In the present study, we found that overexpression of H19 in MAC-T cells significantly promoted cell proliferation, increased the protein and mRNA level of β-casein, and enhanced the expression of tight junction (TJ)-related proteins while inhibitedstaphylococcus aureusadhesion to cells. In addition, results demonstrated that overexpression of H19 affected the LPS-induced immune response of MAC-T cells by promoting expressions of inflammatory factors, including TNF-α, IL-6, CXCL2 and CCL5, and activating the NF-κB signal pathway. Our findings indicate that H19 is likely to play an important role in maintaining normal functions and regulating immune response of bovine mammary epithelial cells.
In vitro and in vivo Investigations of a Sudanese Honey in the Management of Dermatological Fungal Infections
Authors: Suliman Rasha Saad , Ali Heyam Saad , Husayn Abd Araheem , M. A. Elhaj Babiker , Suliman Rania
Published: April 2019

Superficial fungal infections represented 17% of skin diseases in patients attending the outpatient clinic of Khartoum Hospital of Skin and Venereal Diseases.

The treatment of these infections usually involves the use of systemic drugs and/or topical well-tried preparations. All of the drugs carry a potential of adverse reactions, besides their relatively high cost.  Honey, which is a natural product of the honeybee, is believed to be active against fungi.  In this study, honey was used as topical treatment for six different clinical syndromes of superficial fungal infections.

The study, which was carried out at the outpatient clinic of Khartoum Hospital of Skin and Venereal Diseases, included 360 patients (210 males and 150 females) with skin, hair and nail infections. Patients, diagnosed by clinical examination and direct microscopy (KOH), were given honey to be applied on their lesions twice daily.  Follow-up was made weekly by both clinical and laboratory evaluations.  A complementary follow-up visit after 4 weeks of completion of treatment was needed in order to trace any clinical or mycological changes.  Clinical and mycological cure showed some difference.  Two hundred and sixty patients (72.4%) showed clinical cure associated with hyphal clearance on direct microscopy.  Spores were not affected by honey, a direct cause of high relapse rate (42.3%).  It is concluded that honey had a therapeutic effect on skin and scalp fungal infections but nail infection were not affected.
C−O coupling of Malonyl Peroxides with Enol Ethers via [5+2] Cycloaddition: Non‐Rubottom Oxidation
Authors: Vil' Vera A. , Gorlov Evgenii S. , Bityukov Oleg V. , Barsegyan Yana A. , Romanova Yulia E. , Merkulova Valentina M. , Terent'ev Alexander O.
Published: April 2019

Malonyl peroxides act both as oxidants and reagents for C−O coupling in reactions with methyl and silyl enol ethers. In the proposed conditions, the oxidative C−O coupling of malonyl peroxides with enol ethers selectively proceeds, bypassing the traditional Rubottom hydroxylation of enol ethers by peroxides. It was observed that the oxidative [5+2] cycloaddition of malonyl peroxides and enol ethers is the key stage of the discovered process. Oxidative C−O coupling of silyl enol ethers leads to the formation of α‐acyloxyketones with a free carboxylic acid group. A specially developed preparative one‐pot procedure transforms ketones via silyl enol ethers formation and the following coupling into α‐acyloxyketones with yields 35–88%. The acid‐catalyzed coupling with methyl enol ethers gives remarkable products while retaining the easily oxidizable enol fragment. Furthermore, these molecules contain a free carboxylic acid group, thus these nontrivial products contain two usually incompatible acid and enol ether groups.

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A Dual‐Ion Organic Symmetric Battery Constructed from Phenazine‐Based Artificial Bipolar Molecules
Authors: Dai Gaole , He Yan , Niu Zhihui , He Ping , Zhang Changkun , Zhao Yu , Zhang Xiaohong , Zhou Haoshen
Published: April 2019

Symmetric batteries received an increasing research interest in the past few years because of their simplified fabrication process and reduced manufacturing cost. In this study, we propose the first dual‐ion organic symmetric cell based on a molecular anion of 4,4′‐(phenazine‐5,10‐diyl)dibenzoate. The alkali salt of 4,4′‐(phenazine‐5,10‐diyl)dibenzoate allows a facile transport of cations and large anions, and remains stable in both oxidized and reduced states. The large potential difference between phenazine and benzoate results in a high cell voltage of 2.5 V and an energy density of 127 Wh kg−1 at a current rate of 1 C. The introduction of bipolar organic materials may further consolidate the development of symmetric batteries that are fabricated from abundant elements and environmentally friendly materials.
Synthesis and Properties of Azide‐Functionalized Ionic Liquids as Attractive Hypergolic Fuels
Authors: Wang Zhenyuan , Pan Guangxing , Wang Binshen , Zhang Ling , Zhao Weiwei , Ma Xing , Zhang Jichuan , Zhang Jiaheng
Published: April 2019

Hypergolic ionic liquids (ILs) have shown a great promise as viable replacements for toxic and volatile hydrazine derivatives used as propellant fuels, and hence, have attracted increasing interest over the last decade. To take advantage of the reactivity and high energy density of the azido group, a family of low‐cost and easily prepared azide‐functionalized cation‐based ILs, including fuel‐rich anions, such as nitrate, dicyanamide, and nitrocyanamide anions, were synthesized and characterized. All the dicyanamide‐ and nitrocyanamide‐based ILs exhibited spontaneous combustion upon contact with 100 % HNO3. The densities of these hypergolic ILs varied in the range 1.11–1.29 g cm−3, and the density‐specific impulse, predicted based on Gaussian 09 calculations, was between 289.9 and 344.9 s g cm−3. The values of these two key physical properties are much higher than those of unsymmetrical dimethylhydrazine (UDMH). Among the studied compounds, compound IL‐3b, that is, 1‐(2‐azidoethyl)‐1‐methylpyrrolidin‐1‐ium dicyanamide, shows excellent integrated properties including the lowest viscosity (30.9 M Pa s), wide liquid operating range (−70 to 205 °C), shortest ignition‐delay time (7 ms) with 100 % HNO3, and superior density specific impulse (302.5 s g cm−3), suggesting promising applications with potential as bipropellant formulations.
Endovascular stenting for idiopathic intracranial hypertension with venous sinus stenosis
Authors: Liu Xinfeng , Di Hai , Wang Jun , Cao Xiangyu , Du Zhihua , Zhang Rongju , Yu Shengyuan , Li Baomin
Published: April 2019

Objectives

Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure of unknown etiology and venous sinus stenting may be an optional treatment. We aimed to evaluate the effects of venous sinus stenting on visual function, intracranial pressure, and trans‐stenotic pressure gradient of the patients with IIH and to determine effects of baseline BMI or weight changes on subjective vision outcome and intracranial pressure.

Methods

From July 2009 to Aug 2016, 88 eligible patients with IIH and venous sinus stenosis who underwent stenting were retrospectively studied.

Results

In this study, 67 women and 21 men were included with an average age of 39.01 (18–60) years. The average BMI was 26.75 kg/m2. Here, 66 (75.9%) patients had papilledema, 39 had impaired vision before stenting; 57 patients were followed‐up, 48 (84.2%) showed significant subjective improvement or recovery in visual acuity, 4 (7.0%) patients reported no significant change in visual functions, and 5 (8.8%) suffered permanent vision loss. The cerebrospinal fluid opening pressure and trans‐stenotic pressure gradient were significantly decreased postoperatively. Baseline BMI was associated with pre‐and postoperative trans‐stenotic pressure gradients, as well as changes in cerebrospinal fluid opening pressure. However, baseline BMI and body weight changes during follow‐up were not necessarily associated with subjective visual outcomes after stenting. Stenting efficacy was limited in patients with severe preoperative optic symptoms.

Conclusions

Venous sinus stenting represented an effective treatment for resolving visual dysfunction and intracranial pressure associated with venous sinus stenosis. BMI seemed to be associated with intracranial pressure but not subjective visual outcomes after stenting.
Multistage continuous countercurrent diafiltration for formulation of monoclonal antibodies
Authors: Jabra Mario G. , Yehl Christopher J. , Zydney Andrew L.
Published: April 2019

There is growing interest in the development of fully integrated and continuous biomanufacturing processes for the production of monoclonal antibody products. A recent study has demonstrated the feasibility of using a two‐stage countercurrent diafiltration (DF) process for continuous product formulation, but this system did not provide sufficient levels of buffer exchange for most applications. The objective of this study was to design and test a three‐stage countercurrent DF system that could achieve at least 99.9% buffer exchange over 24 hr of continuous operation. Experimental data were obtained using concentrated solutions of human immunoglobulin G as a model protein, with the extent of vitamin B12 removal used to track the extent of DF. Pall Cadence™ inline concentrators with Delta 30 kD regenerated cellulose membranes were used in the three stages to achieve high conversion in a single pass. The three‐stage system showed stable operation with >99.9% vitamin B12 removal and a minimal increase in pressure over the full 24 hr. Modules were effectively cleaned using sodium hydroxide, with nearly complete recovery of water permeability. A simple economic analysis was presented that accounts for the trade‐offs between quantity of buffer used and membrane costs for this type of countercurrent staged DF process. The results provide important insights to the design and operation of a continuous process for antibody formulation.
NEAT1 promotes myocardial ischemia‐reperfusion injury via activating the MAPK signaling pathway
Authors: Du Xian‐Jin , Wei Jie , Tian Dan , Yan Chen , Hu Peng , Wu Xu , Yang Wenbin , Hu Xiaorong
Published: April 2019

Myocardial ischemia‐reperfusion (IR) injury is a common cardiovascular problem, which remains a major cause of death in the world. Emerging evidence has suggested that long noncoding RNAs are crucial players in myocardial injury. However, the functional involvement of nuclear enriched abundant transcript 1 (NEAT1) in myocardial IR injury remains poorly investigated. Our study focused on the mechanism of NEAT1 in myocardial IR injury. Here, we reported a crucial role for NEAT1 in exacerbating cardiac IR injury. NEAT1 was greatly increased in myocardial IR injury mice models. As exhibited knockdown of NEAT1 resulted in attenuated myocardial IR injury in vivo. In addition, we found that NEAT1 was dramatically induced by hypoxia/reoxygenation in H9c2 cells. Lactate dehydrogenase (LDH), malondialdehyde, reactive oxygen species levels, and endoplasmic reticulum stress‐regulated cardiomyocyte apoptosis were inhibited by the downregulation of NEAT1. Here, it was shown that knockdown of NEAT1 was able to repress tumor necrosis factor‐α, interleukin‐1β, and IL‐6 expression. The silence of NEAT1 protected against IR injury via decreasing troponin levels, cardiocytes apoptosis, creatine kinase, and lactate LDH release in vivo. Meanwhile, the mitogen‐activated protein kinase (MAPK) signaling was involved in NEAT1‐mediated myocardial IR injury. In summary, our data indicated that NEAT1 contributed to myocardial IR injury via activating the MAPK pathway.
Activation of the STAT3/microRNA‐21 pathway participates in angiotensin II‐induced angiogenesis
Authors: Chen Li‐Yuan , Wang Xue , Qu Xiao‐Long , Pan Li‐Na , Wang Ze‐Yang , Lu Yong‐Hui , Hu Hou‐Yuan
Published: April 2019

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII‐induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA‐21 (miR‐21) in the AngII‐mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR‐21 was found to be upregulated in AngII‐treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII‐mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR‐21 expression, which was verified by ChIP‐PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR‐21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR‐21, and STAT3 inhibition restored AngII‐induced reduction in PTEN. Similarly, the STAT3/miR‐21 axis was shown to mediate AngII‐provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR‐21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII‐induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.
The role of pretreatment prognostic nutritional index in esophageal cancer: A meta‐analysis
Authors: Xue Yibo , Zhou Xiang , Xue Lei , Zhou Ruhua , Luo Jinhua
Published: April 2019

Clinicopathological characteristics and prognosis of esophageal cancer (EC) patients with decreased prognostic nutritional index (PNI) have not been well investigated. So, we conducted this meta‐analysis. We performed comprehensive research in PubMed, Embase, and Cochrane databases. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) and cancer‐specific survival (CSS). The pooled odds ratio (OR) with 95% CI were used to assess the association between PNI and clinicopathological features. A total of 3,425 EC patients were included in the present meta‐analysis. Male patients, advanced age, higher tumor stage, and lymph node metastases were associated with reduced PNI level (OR = 1.40, 95% CI: 1.10‐1.79; OR = 1.35, 95% CI: 1.10‐1.66; OR = 2.37, 95% CI: 1.91‐2.94; OR = 1.63, 95% CI: 1.04‐2.56). And, the EC patients with decreased PNI held a worse OS and CSS compared with those who carried a higher PNI (HR = 1.29, 95% CI: 1.10‐1.50; HR = 2.53, 95% CI: 1.15‐5.57). This meta‐analysis demonstrated PNI level was associated with tumor stage and lymph nodes metastases and was an independent prognostic factor in EC.
Altering microtubule stability affects microtubule clearance and nuclear extrusion during erythropoiesis
Authors: Xie Songbo , Yan Bing , Feng Jie , Wu Yuhan , He Na , Sun Lei , Zhou Jun , Li Dengwen , Liu Min
Published: April 2019

Mammalian erythrocytes are highly specialized cells that have adapted to lose their nuclei and cellular components during maturation to ensure oxygen delivery. Nuclear extrusion, the most critical event during erythropoiesis, represents an extreme case of asymmetric partitioning that requires a dramatic reorganization of the cytoskeleton. However, the precise role of the microtubule cytoskeleton in the enucleation process remains controversial. In this study, we show that microtubule reorganization is critical for microtubule clearance and nuclear extrusion during erythropoiesis. Using a rodent anemia model, we found that microtubules were present in erythroblasts and reticulocytes but were undetectable in erythrocytes. Further analysis demonstrated that microtubules became disordered in reticulocytes and revealed that microtubule stabilization was critical for tubulin degradation. Disruption of microtubule dynamics using the microtubule‐stabilizing agent paclitaxel or the microtubule‐destabilizing agent nocodazole did not affect the efficiency of erythroblast enucleation. However, paclitaxel treatment resulted in the retention of tubulin in mature erythrocytes, and nocodazole treatment led to a defect in pyrenocyte morphology. Taken together, our data reveals a critical role for microtubules in erythrocyte development. Our findings also implicate the disruption of microtubule dynamics in the pathogenesis of anemia‐associated diseases, providing new insight into the pathogenesis of the microtubule‐targeted agent‐associated anemia frequently observed during cancer chemotherapy.
A lymph node metastasis‐related protein‐coding genes combining with long noncoding RNA signature for breast cancer survival prediction
Authors: Sui Yujie , Ju Chunyan , Shao Bin
Published: April 2019

Integrating protein‐coding gene (PCG) with long noncoding RNA (lncRNA) expression profiles, our aim is to identify a multidimensional transcriptome model that can predict individual prognosis of patients with breast cancer (BRCA). After diverse bioinformatics and statistical analyses, we obtained gene expression profiles of 1,016 BRCA samples from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, and constructed a prognostic signature, which is composed of four PCGs (TFCP2, LRRC75B, PROSER2, and STOML1) and one lncRNA (AL355592.1). In the training set, the multidimensional transcriptome signature could part patients with BRCA into two groups with different survival, defined as high‐ and low‐risk group by Kaplan–Meier (KM) analysis (p < 0.001). In the other five validation datasets, the PCG‐lncRNA signature showed a similar predictive performance in BRCA by KM (p < 0.05). The prognostic independence for the PCG‐lncRNA model was verified by the multivariable Cox regression analysis. Because Chi‐squared test showed the signature was associated with lymph node metastasis status, stratification analysis found that it could further subdivide lymph node metastasis status more precisely in BRCA. The function analysis suggested that the genes from the signature were associated with immunity‐related pathways. In summary, we constructed a PCG‐lncRNA signature, which could accurately predict survival in patients with BRCA.
Effect of strontium substituted ß‐TCP associated to mesenchymal stem cells from bone marrow and adipose tissue on spinal fusion in healthy and ovariectomized rat
Authors: Salamanna Francesca , Giavaresi Gianluca , Contartese Deyanira , Bigi Adriana , Boanini Elisa , Parrilli Annapaola , Lolli Roberta , Gasbarrini Alessandro , Barbanti Brodano Giovanni , Fini Milena
Published: April 2019

Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß‐tricalcium phosphate (Sr‐ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham‐operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr‐ßTCP, Sr‐ßTCP + BMCSs, and Sr‐ßTCP + ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro‐CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr‐ßTCP + BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr‐ßTCP + BMCSs group with Sr‐ßTCP + ADSCs. Radiographical score, based on micro‐CT 2D image, highlighted that the Sr‐ßTCP + BMCSs group presented a similar fusion to Sr‐ßTCP and higher than Sr‐ßTCP + ADSCs in both SHAM and OVX animals. Micro‐CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr‐ßTCP + BMSCs group than Sr‐ßTCP and Sr‐ßTCP + ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr‐ßTCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr‐ßTCP + ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs.
Brefeldin A impairs porcine oocyte meiotic maturation via interruption of organelle dynamics
Authors: Cui Zhaokang , Yu Lingzhu , Shi Yang Xiayan , Zhang Yu , Shi Xiaoyan , Li Yu , Chen Qiuju , Xiong Bo
Published: April 2019

Brefeldin A (BFA) is a lactone antibiotic synthesized from palmitic acid by several fungi that could block anterograde transport of proteins from endoplasmic reticulum to Golgi apparatus by reversible disruption of the Golgi complex. Previous investigations have shown that BFA induces the apoptosis of cancer cells in mitosis and impairs asymmetric spindle positioning in meiosis. Here, we document that exposure to BFA in porcine oocytes compromises the meiotic maturation via disrupting both nuclear and cytoplasmic maturation. We found that BFA exposure collapsed the cytoskeleton assembly by showing the aberrant spindle organization with misaligned chromosomes and defective actin dynamics. Furthermore, the distribution of both mitochondria and cortical granules (CGs), two important indexes of cytoplasmic maturation of oocytes, was disturbed following BFA exposure. We finally validated that the localization of ovastacin, a component of CGs that is essential for the postfertilization removal of sperm‐binding sites in the zona pellucida, was also perturbed in BFA‐exposed oocytes, which might weaken their fertilization capacity. Collectively, these findings indicate that Golgi‐mediated protein transport is indispensable for the porcine oocyte meiotic maturation.
Messenger RNA and protein expression of tumor necrosis factor α and its receptors in human follicular granulosa cells
Authors: Salmassi Ali , Fattahi Amir , Simon Nora , Latifi Zeinab , Ghasemnejad Tohid , Nouri Mohammad , Schmutzler Andreas G.
Published: April 2019

To evaluate the concentration of tumor necrosis factor α (TNF‐α) and its soluble receptors (sTNFR I and II) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of TNF‐α and its receptors by luteinized granulosa cells (GCs). In a cross‐sectional study and through an in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) program, 81 women undergoing oocyte retrieval were recruited. Serum and FF were obtained from 81 women. GCs were pooled from 20 patients (from six different days of oocyte retrievals, 5–16 follicles per patient). TNF‐α and its soluble receptors concentration were determined by enzyme‐linked immunosorbent assay and also their expression by immune cytochemistry and reverse‐transcription polymerase chain reaction analysis. The median TNF‐α concentration in serum was 4.06 pg/ml (interquartile range [IQR], 3.71–6.14) and significantly higher than that in FF with 3.50 pg/ml (IQR, 3.05–5.01), p < 0.001. The sTNFR I and II levels in serum were lower and higher than FF, respectively. The TNF‐α levels in serum and FF of good responders were higher than low responders (p = 0.017 and 0.021, respectively). TNF‐α cut‐off level for low responders versus good responders was 4.174 pg/ml in serum with a pregnancy rate of 25.8% and 40% for below and above of this level, respectively (p = 0.19). For FF, the cut‐off value was 3.89 pg/ml. TNF‐α and its receptors were expressed by GCs. The presence of TNF‐α and its soluble receptors in serum and FF and their expression by GCs suggest an important role for this cytokine in ovarian function.
Demethoxycurcumin: A naturally occurring curcumin analogue for treating non‐cancerous diseases
Authors: Hatamipour Mahdi , Ramezani Mahin , Tabassi Sayyed Abolghasem Sajadi , Johnston Thomas P. , Sahebkar Amirhossein
Published: April 2019

Turmeric extracts contain three primary compounds, which are commonly referred to as curcuminoids. They are curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin. While curcumin has been the most extensively studied of the curcuminoids, it suffers from low overall oral bioavailability due to extremely low absorption as a result of low water solubility and instability at acidic pH, as well as rapid metabolism and clearance from the body. However, DMC, which lacks the methoxy group on the benzene ring of the parent structure, has much greater chemical stability at physiological pH and has been recently reported to exhibit antitumor properties. However, the treatment of noncancerous diseases with DMC has not been comprehensively reviewed. Therefore, here we evaluate published scientific literature on the therapeutic properties of DMC. The beneficial pharmacological actions of DMC include anti‐inflammatory, neuroprotective, antihypertensive, antimalarial, antimicrobial, antifungal, and vasodilatory properties. In addition, DMC's ability to ameliorate the effects of free radicals and an environment characterized by oxidative stress caused by the accumulation of advanced glycation end‐products associated with diabetic nephropathy, as well as DMC's capacity to inhibit the migration and proliferation of vascular smooth muscle cells following balloon angioplasty are also addressed. This review collates the available literature regarding the therapeutic possibilities of DMC in noncancerous conditions.
High expression of SLC38A1 predicts poor prognosis in patients with de novo acute myeloid leukemia
Authors: Li Yan , Shao Haigang , Da Zhenzhen , Pan Jinlan , Fu Bin
Published: April 2019

The glutamine amino acid transporter solute carrier family 38 member 1 (SLC38A1) is associated with the occurrence and progression of solid tumors. However, it has not yet been assessed in patients with hematologic malignancy. Herein, we investigated SLC38A1 expression and explored its clinical implications in acute myeloid leukemia (AML). The results showed that patients with high SLC38A1 expression had a lower mutation rate of NPM1 gene and higher incidence of adverse‐risk karyotype (p = 0.0010 and 0.0051, respectively). Patients with a high level of SLC38A1 expression presented significantly shorter overall survival in whole‐cohort, chemotherapy‐only, and non‐inv(16) AML (p = 0.0049, 0.0247, and 0.0005 respectively). Moreover, both univariate and multivariate analyses showed that high SLC38A1 expression was an independent unfavorable prognostic biomarker for AML (p = 0.0057 and 0.0483, respectively). In summary, our study revealed SLC38A1 as a valuable prognostic and predictive marker for AML. Further, glutamine transporter SLC38A1 might serve as a potential target for the development of novel therapeutic drugs in the treatment of AML.
Effects of extrusion types, screw speed and addition of wheat gluten on physicochemical characteristics and cooking stability of meat analogues
Authors: Samard Sasimaporn , Gu Bon‐Yeob , Ryu Gi‐Hyung
Published: April 2019

BACKGROUND

Plant protein‐based products such as meat analogues have been receiving attention over the years. However, comparisons of product properties and mechanisms applied in the production of low‐ and high‐moisture meat analogues have not been reported. In this study, the effects of extrusion types (low‐ and high‐moisture extrusion cooking), absence or presence of added wheat gluten, as well as screw speed (150 and 200 rpm) on the physicochemical properties of meat analogues were evaluated. The mechanism of protein texturization of low‐ and high‐moisture meat analogues was studied.

RESULTS

Extrusion types and addition of wheat gluten had a major influence on physicochemical characteristics which were critical in controlling the fibrous texture of the final product, while screw speed had a minor impact on springiness only (P < 0.001). All high‐moisture meat analogues (HMMAs) were associated with a higher integrity index and greater stability of springiness and cutting strength than low‐moisture meat analogues (LMMAs) using the same formula and screw speed, while the nitrogen solubility index of HMMAs was lower. Based on the physicochemical properties determined, the higher cross‐link formation in HMMAs is proposed to occur in the cooling die section.

CONCLUSION

Our findings show that the utilization of high‐moisture extrusion cooking and the incorporation of wheat gluten into the formula at 400 g kg−1 could impart a fibrous and compact structure to extrudates similar to that of actual muscle meat, with a greater integrity index and texture stability. © 2019 Society of Chemical Industry
Outcomes analysis of Goldilocks mastectomy and breast reconstruction: A single institution experience of 96 cases
Authors: Chaudhry Arif , Oliver Jeremie D. , Vyas Krishna S. , Alsubaie Saad A. , Manrique Oscar J. , Martinez‐Jorge Jorys
Published: April 2019

Background

The Goldilocks mastectomy procedure involves local contouring of completely autologous breast tissue created by preserving and de‐epithelializing the residual mastectomy flaps. The purpose of this study was to provide outcomes data for 96‐Goldilocks mastectomy procedures analyzing indications, complications, relevant comorbidities, and adjuvant cancer treatment impacting reconstructive and aesthetic outcomes.

Methods

Comprehensive review of every patient who underwent Goldilocks mastectomy from 2012 to 2018 included relevant medical and surgical comorbidities, as well as complication profiles. Aesthetic outcomes were also assessed in those with postoperative imaging available.

Results

A total of 53 patients (96 breasts) were included in this study. Bilateral cases consisted of 81.1% of the total cohort (n = 86 cases), and 18.9% (n = 10 cases) were unilateral procedures. Mean age at the time of reconstruction was 55.8 (33‐77) years. Mean body mass index (BMI) at the time of reconstruction was 33.7 (19.2‐54.6). The overall complication rate was 9.38% (seroma = 2, hematoma = 1, cellulitis = 2, wound dehiscence = 3, and operating room take back = 1).

Conclusions

Goldilocks breast reconstruction is a safe, effective option in patients with higher than average BMI or excess local breast tissue, or in patients meeting these criteria preferring a single‐stage reconstruction. This study qualifies its use in patients with higher than average risk factors for more extensive reconstructive modalities.
Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection
Authors: Samkoe Kimberley S. , Sardar Hira S. , Bates Brent D. , Tselepidakis Niki N. , Gunn Jason R. , Hoffer‐Hawlik Kevin A. , Feldwisch Joachim , Pogue Brian W. , Paulsen Keith D. , Henderson Eric R.
Published: April 2019

Background and Objectives

Fluorescence‐guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY‐029 (anti‐EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small‐molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft‐tissue sarcomas with varying levels of EGFR expression and vascularization.

Methods

Five xenograft soft‐tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY‐029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin‐fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues.

Results

ABY‐029 is retained longer within tumor tissue and achieves higher tumor‐to‐background ratios both in vivo and ex vivo than IRDye 700DX. ABY‐029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast‐to‐noise ratio, but all systems have individual advantages.

Conclusions

ABY‐029 demonstrates promise to assist in wide local excision of soft‐tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.
What if something unexpected happens to my brand? Spillover effects from positive and negative events in a co‐branding partnership
Authors: Koschate‐Fischer Nicole , Hoyer Wayne D. , Wolframm Christiane
Published: April 2019

Brands sometimes enter into co‐branding agreements and major events can occur to one of the brands which can have either negative or positive consequences for the brands involved in the partnership. The current study investigates as yet unanswered research questions regarding whether and how positive and negative events happening to one brand in a co‐branding partnership affect the brand equities of the other brands in the partnership. The authors provide and test a new integrated attribution‐diagnosticity framework to explain the process that underlies the magnitude of these spillover effects. Findings show that while positive and negative event‐related spillover effects occur between the co‐brand and both parent brands, they were surprisingly absent between the parent brands. Further, the (a)symmetry of parent brand equity before the event influences the magnitude of event‐related spillover the parent brands receive from the co‐brand. Theoretical and practical implications of these findings are discussed.
A size‐dependent Bernoulli‐Euler beam model based on strain gradient elasticity theory incorporating surface effects
Authors: Fu Guangyang , Zhou Shenjie , Qi Lu
Published: April 2019

In this paper, a size‐dependent model for Bernoulli‐Euler beam is developed by using a general strain gradient theory and a surface elasticity theory. The general strain gradient theory is used to capture the strain gradient effects while the surface elasticity theory is applied to explain the surface effects. As comparison, the approximate theories including the couple stress theory and the simplified strain gradient theory are also used to describe the strain gradient effects. The Hamilton's principle is used to derive the governing equations, boundary conditions and initial conditions. The static bending and free vibration behaviour of nanobeams with different boundary conditions are analysed. Compared with the results predicted by the couple stress theory with surface effects and the simplified strain gradient theory with surface effects, because the general strain gradient theory contains the influences of all strain gradients, the deflection predicted by the general strain gradient theory with surface effects is smallest while the natural frequency is highest. The general strain gradient theory reflects size effects more accurately.
Universal Graphs and Good for Games Automata: New Tools for Infinite Duration Games
Authors: Colcombet Thomas , Fijalkow Nathanaël
Published: April 2019

In this paper, we give a self contained presentation of a recent breakthrough in the theory of infinite duration games: the existence of a quasipolynomial time algorithm for solving parity games. We introduce for this purpose two new notions: good for small games automata and universal graphs.

The first object, good for small games automata, induces a generic algorithm for solving games by reduction to safety games. We show that it is in a strong sense equivalent to the second object, universal graphs, which is a combinatorial notion easier to reason with. Our equivalence result is very generic in that it holds for all existential memoryless winning conditions, not only for parity conditions.
Two-Way Parikh Automata with a Visibly Pushdown Stack
Authors: Dartois Luc , Filiot Emmanuel , Talbot Jean-Marc
Published: April 2019

In this paper, we investigate the complexity of the emptiness problem for Parikh automata equipped with a pushdown stack. Pushdown Parikh automata extend pushdown automata with counters which can only be incremented and an acceptance condition given as a semi-linear set, which we represent as an existential Presburger formula over the final values of the counters. We show that the non-emptiness problem both in the deterministic and non-deterministic cases is . If the input head can move in a two-way fashion, emptiness gets undecidable, even if the pushdown stack is visibly and the automaton deterministic. We define a restriction, called the single-use restriction, to recover decidability in the presence of two-wayness, when the stack is visibly. This syntactic restriction enforces that any transition which increments at least one dimension is triggered only a bounded number of times per input position. Our main contribution is to show that non-emptiness of two-way visibly Parikh automata which are single-use is NExpTime-c. We finally give applications to decision problems for expressive transducer models from nested words to words, including the equivalence problem.
Trees in Partial Higher Dimensional Automata
Authors: Dubut Jérémy
Published: April 2019

In this paper, we give a new definition of partial Higher Dimension Automata using lax functors. This definition is simpler and more natural from a categorical point of view, but also matches more clearly the intuition that pHDA are Higher Dimensional Automata with some missing faces. We then focus on trees. Originally, for example in transition systems, trees are defined as those systems that have a unique path property. To understand what kind of unique property is needed in pHDA, we start by looking at trees as colimits of paths. This definition tells us that trees are exactly the pHDA with the unique path property modulo a notion of homotopy, and without any shortcuts. This property allows us to prove two interesting characterisations of trees: trees are exactly those pHDA that are an unfolding of another pHDA; and trees are exactly the cofibrant objects, much as in the language of Quillen’s model structure. In particular, this last characterisation gives the premisses of a new understanding of concurrency theory using homotopy theory.
The Bernays-Schönfinkel-Ramsey Class of Separation Logic on Arbitrary Domains
Authors: Echenim Mnacho , Iosif Radu , Peltier Nicolas
Published: April 2019

This paper investigates the satisfiability problem for Separation Logic with k record fields, with unrestricted nesting of separating conjunctions and implications, for prenex formulæ with quantifier prefix $$\exists ^*\forall ^*$$. In analogy with first-order logic, we call this fragment Bernays-Schönfinkel-Ramsey Separation Logic [$$\mathsf {BSR}(\mathsf {SL}^{\!\scriptstyle {k}})$$]. In contrast to existing work in Separation Logic, in which the universe of possible locations is assumed to be infinite, both finite and infinite universes are considered. We show that, unlike in first-order logic, the (in)finite satisfiability problem is undecidable for $$\mathsf {BSR}(\mathsf {SL}^{\!\scriptstyle {k}})$$. Then we define two non-trivial subsets thereof, that are decidable for finite and infinite satisfiability respectively, by controlling the occurrences of universally quantified variables within the scope of separating implications, as well as the polarity of the occurrences of the latter. Beside the theoretical interest, our work has natural applications in program verification, for checking that constraints on the shape of a data-structure are preserved by a sequence of transformations.