bluuebunny/crossref_metadata_2025_split huggingface dataset:
The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma
Authors: Coltherd J. C. , Rodgers D. T. , Lawrie R. E. , Al-Riyami L. , Suckling C. J. , Harnett W. , Harnett M. M. 
Published: January 2016

AbstractChronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma.
DNA supercoiling, a critical signal regulating the basal expression of the lac operon in Escherichia coli
Authors: Fulcrand Geraldine , Dages Samantha , Zhi Xiaoduo , Chapagain Prem , Gerstman Bernard S. , Dunlap David , Leng Fenfei 
Published: January 2016

AbstractEscherichia coli lacrepressor (LacI) is a paradigmatic transcriptional factor that controls the expression oflacZYAin thelacoperon. This tetrameric protein specifically binds to theO1,O2andO3operators of thelacoperon and forms a DNA loop to repress transcription from the adjacentlacpromoter. In this article, we demonstrate that upon binding to theO1andO2operators at their native positions LacI constrains three (−) supercoils within the 401-bp DNA loop of thelacpromoter and forms a topological barrier. The stability of LacI-mediated DNA topological barriers is directly proportional to its DNA binding affinity. However, we find that DNA supercoiling modulates the basal expression from thelacoperon inE. coli. Our results are consistent with the hypothesis that LacI functions as a topological barrier to constrain free, unconstrained (−) supercoils within the 401-bp DNA loop of thelacpromoter. These constrained (−) supercoils enhance LacI’s DNA-binding affinity and thereby the repression of the promoter. Thus, LacI binding is superhelically modulated to control the expression oflacZYAin thelac operonunder varying growth conditions.
Modular structure of brain functional networks: breaking the resolution limit by Surprise
Authors: Nicolini Carlo , Bifone Angelo 
Published: January 2016

AbstractThe modular organization of brain networks has been widely investigated using graph theoretical approaches. Recently, it has been demonstrated that graph partitioning methods based on the maximization of global fitness functions, like Newman’s Modularity, suffer from a resolution limit, as they fail to detect modules that are smaller than a scale determined by the size of the entire network. Here we explore the effects of this limitation on the study of brain connectivity networks. We demonstrate that the resolution limit prevents detection of important details of the brain modular structure, thus hampering the ability to appreciate differences between networks and to assess the topological roles of nodes. We show that Surprise, a recently proposed fitness function based on probability theory, does not suffer from these limitations. Surprise maximization in brain co-activation and functional connectivity resting state networks reveals the presence of a rich structure of heterogeneously distributed modules and differences in networks’ partitions that are undetectable by resolution-limited methods. Moreover, Surprise leads to a more accurate identification of the network’s connector hubs, the elements that integrate the brain modules into a cohesive structure.
Experimental Model for Successful Liver Cell Therapy by Lenti TTR-YapERT2 Transduced Hepatocytes with Tamoxifen Control of Yap Subcellular Location
Authors: Yovchev Mladen , Jaber Fadi L. , Lu Zhonglei , Patel Shachi , Locker Joseph , Rogler Leslie E. , Murray John W. , Sudol Marius , Dabeva Mariana D. , Zhu Liang , Shafritz David A. 
Published: January 2016

AbstractLiver repopulation by transplanted hepatocytes has not been achieved previously in a normal liver microenvironment. Here we report that adult rat hepatocytes transduced ex vivo with a lentivirus expressing a human YapERT2 fusion protein (hYapERT2) under control of the hepatocyte-specific transthyretin (TTR) promoter repopulate normal rat liver in a tamoxifen-dependent manner. Transplanted hepatocytes expand very slowly but progressively to produce 10% repopulation at 6 months, showing clusters of mature hepatocytes that are fully integrated into hepatic parenchyma, with no evidence for dedifferentiation, dysplasia or malignant transformation. Thus, we have developed the first vector designed to regulate the growth control properties of Yap that renders it capable of producing effective cell therapy. The level of liver repopulation achieved has significant translational implications, as it is 2-3x the level required to cure many monogenic disorders of liver function that have no underlying hepatic pathology and is potentially applicable to diseases of other tissues and organs.
Accurate quantification of creatinine in serum by coupling a measurement standard to extractive electrospray ionization mass spectrometry
Authors: Huang Keke , Li Ming , Li Hongmei , Li Mengwan , Jiang You , Fang Xiang 
Published: January 2016

AbstractAmbient ionization (AI) techniques have been widely used in chemistry, medicine, material science, environmental science, forensic science. AI takes advantage of direct desorption/ionization of chemicals in raw samples under ambient environmental conditions with minimal or no sample preparation. However, its quantitative accuracy is restricted by matrix effects during the ionization process. To improve the quantitative accuracy of AI, a matrix reference material, which is a particular form of measurement standard, was coupled to an AI technique in this study. Consequently the analyte concentration in a complex matrix can be easily quantified with high accuracy. As a demonstration, this novel method was applied for the accurate quantification of creatinine in serum by using extractive electrospray ionization (EESI) mass spectrometry. Over the concentration range investigated (0.166 ~ 1.617 μg/mL), a calibration curve was obtained with a satisfactory linearity (R2 = 0.994) and acceptable relative standard deviations (RSD) of 4.6 ~ 8.0% (n = 6). Finally, the creatinine concentration value of a serum sample was determined to be 36.18 ± 1.08 μg/mL, which is in excellent agreement with the certified value of 35.16 ± 0.39 μg/mL.
One-Minute Room-Temperature Transfer-Free Production of Mono- and Few-Layer Polycrystalline Graphene on Various Substrates
Authors: Jiang Shenglin , Zeng Yike , Zhou Wenli , Miao Xiangshui , Yu Yan 
Published: January 2016

AbstractGraphene deposited on various substrates has attracted the attention of the scientific and technical communities for use in a wide range of applications. Graphene on substrates is commonly produced by two types of methods, namely, methods that require a transfer step and transfer-free methods. Compared with methods that require a transfer step, transfer-free methods have a simpler procedure and a lower cost. Thus, transfer-free methods have considerable potential to meet the industrial and commercial demands of production methods. However, some limitations of the current transfer-free methods must be overcome, such as the high temperatures encountered during production, the relatively long manufacturing times, incompatibilities for both rigid and flexible substrates and an inability to extend the process to other two-dimensional (2-D) atomic crystals. In this work, a room-temperature rubbing method is developed for the rapid transfer-free production of defect-free polycrystalline graphene on rigid and flexible substrates. Starting with inexpensive commercially obtained graphite powder, mono- and few-layer graphene can be fabricated directly on various substrates, with an average production time of less than one minute (from raw graphite to graphene on the substrate). Importantly, this method can be extended to other 2-D atomic crystals.
Joint Effects of Intraocular Pressure and Myopia on Risk of Primary Open-Angle Glaucoma: The Singapore Epidemiology of Eye Diseases Study
Authors: Tham Yih-Chung , Aung Tin , Fan Qiao , Saw Seang-Mei , Siantar Rosalynn Grace , Wong Tien Y. , Cheng Ching-Yu 
Published: January 2016

AbstractWe examined the joint effects of intraocular pressure (IOP) and myopia on the risk of primary open angle glaucoma (POAG) in a multi-ethnic Asian population. A total of 9,422 participants (18,469 eyes) in the Singapore Epidemiology of Eye Diseases Study were included. Of them, 213 subjects (273 eyes) had POAG. All participants underwent standardised examinations. The independent and joint effects of IOP and myopia on POAG were examined using logistic regression models. Generalised estimating equation models were used to account for correlation between eyes. Higher IOP, longer axial length and more negative spherical equivalent were independently associated with POAG, after adjusting for relevant covariates (all P ≤ 0.005). Significant interaction between IOP and myopia on POAG was observed (P interaction = 0.025). Eyes with moderate-to-high myopia (<−3.0 dioptres) with high IOP (≥20 mmHg) were 4.27 times (95% CI, 2.10–8.69) likely to have POAG, compared to eyes without myopia (>−0.5 dioptres) and with IOP <20 mmHg. Eyes with AL of ≥25.5 mm and high IOP (≥20 mmHg) were 16.22 times (95% CI, 7.73 to 34.03) likely to have POAG, compared to eyes with shorter AL (<23.5 mm) and lower IOP (<20 mmHg). These findings may provide additional insights into the pathophysiology of POAG and are particularly relevant for Asian populations.
Hyperuniform disordered terahertz quantum cascade laser
Authors: Degl’Innocenti R. , Shah Y. D. , Masini L. , Ronzani A. , Pitanti A. , Ren Y. , Jessop D. S. , Tredicucci A. , Beere H. E. , Ritchie D. A. 
Published: January 2016

AbstractLaser cavities have been realized in various different photonic systems. One of the forefront research fields regards the investigation of the physics of amplifying random optical media. The random laser is a fascinating concept because, further to the fundamental research investigating light transport into complex media, it allows us to obtain non-conventional spectral distribution and angular beam emission patterns not achievable with conventional approaches. Even more intriguing is the possibility to engineera priorithe optical properties of a disordered distribution in an amplifying medium. We demonstrate here the realization of a terahertz quantum cascade laser in an isotropic hyperuniform disordered distribution exhibiting unique features, such as the presence of a photonic band gap, low threshold current density, unconventional angular emission and optical bistability.
Novel Methods of Determining Urinary Calculi Composition: Petrographic Thin Sectioning of Calculi and Nanoscale Flow Cytometry Urinalysis
Authors: Gavin Carson T , Ali Sohrab N , Tailly Thomas , Olvera-Posada Daniel , Alenezi Husain , Power Nicholas E , Hou Jinqiang , St. Amant Andre H , Luyt Leonard G , Wood Stephen , Wu Charles , Razvi Hassan , Leong Hon S 
Published: January 2016

AbstractAccurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected during surgery subsequently underwent petrographic thin sectioning with polarized and fluorescent microscopy. Fluorescently labeled bisphosphonate probes (Alendronate-fluorescein/Alendronate-Cy5) were developed for nanoscale flow cytometry to enumerate nanocrystals that bound the fluorescent probes. Petrographic sections of stones were also imaged by fluorescent and polarized light microscopy with composition analysis correlated to alendronate +ve nanocrystal counts in corresponding urine samples. Urine samples from patients with Ca2+ and Mg2+ based calculi exhibited the highest alendronate +ve nanocrystal counts, ranging from 100–1000 nm in diameter. This novel urine based assay was in agreement with composition determined by petrographic thin sections with Alendronate probes. In some cases, high alendronate +ve nanocrystal counts indicated a Ca2+ or Mg2+ composition, as confirmed by petrographic analysis, overturning initial spectrophotometric diagnosis of stone composition. The combination of nanoscale flow cytometry and petrographic thin sections offer an alternative means for determining stone composition. Nanoscale flow cytometry of alendronate +ve nanocrystals alone may provide a high-throughput means of evaluating stone burden.
Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration
Authors: Zhang Xingdi , Zeng Deliang , Li Nan , Wen Jin , Jiang Xinquan , Liu Changsheng , Li Yongsheng 
Published: January 2016

AbstractMesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process.
Attentional biases to faces expressing disgust in children with autism spectrum disorders: an exploratory study
Authors: Zhao Xin , Zhang Peng , Fu Li , Maes Joseph H. R. 
Published: January 2016

AbstractPrevious studies on attentional bias towards emotional faces in individuals with autism spectrum disorders (ASD) provided mixed results. This might be due to differences in the examined attentional bias components and emotional expressions. This study assessed three bias components, hypervigilance, disengagement and avoidance, using faces with a disgust, happy, or neutral expression in a dot-probe and external cuing task in 18 children with ASD and 21 typically developing (TD) children. The children with ASD initially displayed hypervigilance towards the disgust faces, followed by a general tendency to avoid looking back at the spatial location at which any face, irrespective of its emotional expression, had been presented. These results highlight the importance of differentiating between attentional bias components in research on ASD.
Identification of a novel family of carbohydrate-binding modules with broad ligand specificity
Authors: Duan Cheng-Jie , Feng Yu-Liang , Cao Qi-Long , Huang Ming-Yue , Feng Jia-Xun 
Published: January 2016

AbstractMost enzymes that act on carbohydrates include non-catalytic carbohydrate-binding modules (CBMs) that recognize and target carbohydrates. CBMs bring their appended catalytic modules into close proximity with the target substrate and increase the hydrolytic rate of enzymes acting on insoluble substrates. We previously identified a novel CBM (CBMC5614-1) at the C-terminus of endoglucanase C5614-1 from an uncultured microorganism present in buffalo rumen. In the present study, that the functional region of CBMC5614-1 involved in ligand binding was localized to 134 amino acids. Two representative homologs of CBMC5614-1, sharing the same ligand binding profile, targeted a range of β-linked polysaccharides that adopt very different conformations. Targeted substrates included soluble and insoluble cellulose, β-1,3/1,4-mixed linked glucans, xylan and mannan. Mutagenesis revealed that three conserved aromatic residues (Trp-380, Tyr-411 and Trp-423) play an important role in ligand recognition and targeting. These results suggest that CBMC5614-1 and its homologs form a novel CBM family (CBM72) with a broad ligand-binding specificity. CBM72 members can provide new insight into CBM-ligand interactions and may have potential in protein engineering and biocatalysis.
Establishment of a novel in vitro model of stratified epithelial wound healing with barrier function
Authors: Gonzalez-Andrades Miguel , Alonso-Pastor Luis , Mauris Jérôme , Cruzat Andrea , Dohlman Claes H. , Argüeso Pablo 
Published: January 2016

AbstractThe repair of wounds through collective movement of epithelial cells is a fundamental process in multicellular organisms. In stratified epithelia such as the cornea and skin, healing occurs in three steps that include a latent, migratory and reconstruction phases. Several simple and inexpensive assays have been developed to study the biology of cell migration in vitro. However, these assays are mostly based on monolayer systems that fail to reproduce the differentiation processes associated to multilayered systems. Here, we describe a straightforward in vitro wound assay to evaluate the healing and restoration of barrier function in stratified human corneal epithelial cells. In this assay, circular punch injuries lead to the collective migration of the epithelium as coherent sheets. The closure of the wound was associated with the restoration of the transcellular barrier and the re-establishment of apical intercellular junctions. Altogether, this new model of wound healing provides an important research tool to study the mechanisms leading to barrier function in stratified epithelia and may facilitate the development of future therapeutic applications.
DL-3-n-butylphthalide delays the onset and progression of diabetic cataract by inhibiting oxidative stress in rat diabetic model
Authors: Wang Fuxu , Ma Jia , Han Fei , Guo Xiujin , Meng Li , Sun Yufeng , Jin Cheng , Duan Huijun , Li Hang , Peng Ying 
Published: January 2016

AbstractDL-3-n-butylphthalide (NBP) is a therapeutic drug used for ischemic stroke treatment. Here, we investigated the impact of NBP on the development of rat diabetic cataract induced by intraperitoneal injection of streptozotocin (STZ). NBP was then administrated by oral gavage for nine weeks. Cataract development was monitored through ophthalmoscope inspections. The levels of blood glucose and serum reactive oxygen species (ROS), malondialdehyde (MDA) and 8-Hydroxydeovexyguanosine (8-OHdG) were measured. Total and soluble protein and oxidative stress parameters, such as 2, 4- dinitrophenylhydrazone (DNP), 4-hydroxynonenal (4-HNE) and MDA in the lenses were determined by Western blot and thiobarbituric acid analyses. The expressions of NF-E2-related factor 2 (Nrf2) and its downstream antioxidant enzymes, thioredoxin (TRX), Catalase and nuclear accumulation of Nrf2 were determined by Western blot and immunohistochemistry analyses. We showed that NBP treatment significantly improved the cataract scores, the levels of DNP, 4-HNE and MDA in the lens compared to the non-treated groups. NBP also enhanced the expressions of Nrf2, TRX and catalase in the lens of diabetic rats. In addition, NBP treatment also decreased levels of blood glucose, serum MDA and 8-OHdG. These results suggested that NBP treatment significantly delayed the onset and progression of diabetic cataract by inhibiting the oxidative stresses.
Endothelial Cords Promote Tumor Initial Growth prior to Vascular Function through a Paracrine Mechanism
Authors: Zhao Chengjian , Zhang Wei , Zhao Yuwei , Yang Yun , Luo Hui , Ji Gaili , Dong E , Deng Hongxing , Lin Shuo , Wei Yuquan , Yang Hanshuo 
Published: January 2016

AbstractThe angiogenic switch is an important oncogenic step that determines whether microtumors remain dormant or progresses further. It has been generally perceived that the primary function of this tumorgenic event is to supply oxygen and nutrients through blood circulation. Using in vivo imaging of zebrafish and mouse tumor models, we showed that endothelial cords aggressively penetrated into microtumors and remained non-circulatory for several days before undergoing vascular blood perfusion. Unexpectedly, we found that initial tumor growth in both models was significantly reduced if endothelial cords were removed by blocking VEGF-VEGFR2 signaling or using a vascular deficient zebrafish mutant. It was further shown that soluble factors including IL-8, secreted by endothelial cells (ECs) were responsible for stimulating tumor cells proliferation. These findings establish that tumor angiogenesis play a much earlier and broader role in promoting tumor growth, which is independent of vascular circulation. Understanding this novel mechanism of angiogenic tumor progression offers new entry points for cancer therapeutics.
DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders
Authors: Wang Fan , Xu Hongqin , Zhao Hongyu , Gelernter Joel , Zhang Huiping 
Published: January 2016

AbstractDNA methylome alterations in the prefrontal cortex (PFC) may contribute to risk for alcohol use disorders (AUDs). We examined postmortem PFC DNA methylomes of 16 male and seven female pairs of AUD and control subjects using Illumina’s HumanMethylation450 BeadChip assays. In male AUD subjects, 1,812 CpGs (1,099 genes) were differentially methylated (9.5 × 10−9 ≤ Pnominal ≤ 7.2 × 10−4, q < 0.05). In females, no CpGs were associated with AUDs after multiple testing correction (q > 0.05). Twenty-one AUD-associated co-methylation modules were identified in males by co-methylation analysis. The 1,812 CpGs were over-presented by two AUD-associated co-methylation modules (Mturquoise: 1,048 CpGs/683 genes; Mblue: 429 CpGs/304 genes) (Phyper ≤ 0.001). Biological processes enriched for genes in these two modules included neural development and transcriptional regulation. Genes mapped by CpGs in these two modules were enriched in genome-wide association study-identified genes with variants associated with four substance dependence phenotypes or five psychiatric disorders. Additionally, 106 of the 1,812 CpGs were mapped to 93 genes (e.g., AUD-associated genes GRIK3, GRIN2C and GABRA1) with differential expression in postmortem PFC of male AUD subjects. Our study demonstrates that DNA methylation alterations in the PFC are associated with (and might result in) increased risk of AUDs and there was a complex DNA methylation-gene expression relationship.