bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice
Authors: Diao Fan , Jiang Chen , Wang Xiu-Xing , Zhu Rui-Lou , Wang Qiang , Yao Bing , Li Chao-Jun 
Published: July 2016

AbstractSpermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility. Now we further explored the role of protein prenylation in germ cells, using a conditional deletion of geranylgeranyl diphosphate synthase (Ggpps) in embryonic stage and postmeiotic stage respectively. We observed infertility ofGgpps−/−Ddx4-Cre mice that displayed a Sertoli-cell-only syndrome phenotype, which resulted from abnormal spermatogonial differentiation and SSC depletion during the prepubertal stage. Analysis of morphological characteristics and cell-specific markers revealed that spermatogonial differentiation was enhanced from as early as the 7thpostnatal day in the first round of spermatogenesis. Studies of the molecular mechanisms indicated thatGgppsdeletion enhanced Rheb farnesylation, which subsequently activated mTORC1 and facilitated spermatogonial differentiation. In conclusion, the prenylation balance in germ cells is crucial for spermatogonial differentiation fate decision during the prepubertal stage and the disruption of this process results in primary infertility.
Expression of dynein, cytoplasmic 2, heavy chain 1 (DHC2) associated with glioblastoma cell resistance to temozolomide
Authors: Wang Hai , Feng Wenfeng , Lu Yuntao , Li Hezhen , Xiang Wei , Chen Ziyang , He Minyi , Zhao Liang , Sun Xuegang , Lei Bingxi , Qi Songtao , Liu Yawei 
Published: July 2016

AbstractTemozolomide (TMZ) is the main chemotherapeutic drug utilized for the treatment of glioblastoma multiforme (GMB), however, drug resistance often leads to tumor recurrence and poor outcomes. GMB cell lines were treated with TMZ for up to two weeks and then subjected to proteomics analysis to identify the underlying molecular pathology that is associated with TMZ resistance. Proteomics data showed that TMZ altered expression of proteins that related to cytoskeleton structure and function, such as DHC2 and KIF2B. qRT-PCR and immunofluorescence were used to verify expression of DHC2 and KIF2B in these cells. Immunohistochemistry was used to verify expression of these two proteins in xenografts of a nude mouse model and ex vivo GBM tissue samples. Their expression was knocked down using siRNA to confirm their role in the regulation of GBM cell sensitivity to TMZ. Knockdown of DHC2 expression enhanced sensitivity of U87 cells to TMZ treatment. Ex vivo data showed that DHC2 expression in GBM tissue samples was associated with tumor recurrence after TMZ chemotherapy. These results indicated cytoskeleton related protein DHC2 reduced sensitivity of GBM cells to TMZ treatment. Further studies should assess DHC2 as a novel target in GBM for TMZ combination treatment.
Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration
Authors: Grunin Michelle , Hagbi-Levi Shira- , Rinsky Batya , Smith Yoav , Chowers Itay 
Published: July 2016

AbstractMononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene-expression signature in peripheral blood mononuclear cells from AMD patients and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-naïve neovascular AMD (nvAMD) patients (n = 14) and age-matched controls (n = 15) and performed microarray and bioinformatics analysis. Quantitative real-time PCR was performed on other sets of nvAMD (n = 25), atrophic AMD (n = 21) and controls (n = 28) for validation. This validated microarray genes (like TMEM176A/B and FOSB) tested, including differences between nvAMD and atrophic AMD. We identified 2,165 differentially-expressed genes (P < 0.05), including 79 genes with log2 fold change ≥1.5 between nvAMD and controls. Functional annotation using DAVID and TANGO demonstrated immune response alterations in AMD monocytes (FDR-P <0.05), validated by randomized data comparison (P < 0.0001). GSEA, ISMARA and MEME analysis found immune enrichment and specific involved microRNAs. Enrichment of differentially-expressed genes in monocytes was found in retina via SAGE data-mining. These genes were enriched in non-classical vs. classical monocyte subsets (P < 0.05). Therefore, global gene expression analysis in AMD monocytes reveals an altered immune-related signature, further implicating systemic MP activation in AMD.
Observations of movement dynamics of flying insects using high resolution lidar
Authors: Kirkeby Carsten , Wellenreuther Maren , Brydegaard Mikkel 
Published: July 2016

AbstractInsects are fundamental to ecosystem functioning and biodiversity, yet the study of insect movement, dispersal and activity patterns remains a challenge. Here we present results from a novel high resolution laser-radar (lidar) system for quantifying flying insect abundance recorded during one summer night in Sweden. We compare lidar recordings with data from a light trap deployed alongside the lidar. A total of 22808 insect were recorded and the relative temporal quantities measured matched the quantities recorded with the light trap within a radius of 5 m. Lidar records showed that small insects (wing size <2.5 mm2 in cross-section) moved across the field and clustered near the light trap around 22:00 local time, while larger insects (wing size >2.5 mm2 in cross-section) were most abundant near the lidar beam before 22:00 and then moved towards the light trap between 22:00 and 23:30. We could distinguish three insect clusters based on morphology and found that two contained insects predominantly recorded above the field in the evening, whereas the third was formed by insects near the forest at around 21:30. Together our results demonstrate the capability of lidar for distinguishing different types of insect during flight and quantifying their movements.
Highly sensitive gas-phase explosive detection by luminescent microporous polymer networks
Authors: Räupke André , Palma-Cando Alex , Shkura Eugen , Teckhausen Peter , Polywka Andreas , Görrn Patrick , Scherf Ullrich , Riedl Thomas 
Published: July 2016

AbstractWe propose microporous networks (MPNs) of a light emitting spiro-carbazole based polymer (PSpCz) as luminescent sensor for nitro-aromatic compounds. The MPNs used in this study can be easily synthesized on arbitrarily sized/shaped substrates by simple and low-cost electrochemical deposition. The resulting MPN afford an extremely high specific surface area of 1300 m2/g, more than three orders of magnitude higher than that of the thin films of the respective monomer. We demonstrate, that the luminescence of PSpCz is selectively quenched by nitro-aromatic analytes, e.g. nitrobenzene, 2,4-DNT and TNT. In striking contrast to a control sample based on non-porous spiro-carbazole, which does not show any luminescence quenching upon exposure to TNT at levels of 3 ppm and below, the microporous PSpCz shows a clearly detectable response even at TNT concentrations as low as 5 ppb, clearly demonstrating the advantage of microporous films as luminescent sensors for traces of explosive analytes. This level states the vapor pressure of TNT at room temperature.
Molecular characterization and analysis of high-level multidrug-resistance of Shigella flexneri serotype 4s strains from China
Authors: Yang Chaojie , Li Peng , Zhang Xiujuan , Ma Qiuxia , Cui Xianyan , Li Hao , Liu Hongbo , Wang Jian , Xie Jing , Wu Fuli , Sheng Chunyu , Du Xinying , Qi Lihua , Su Wenli , Jia Leili , Xu Xuebin , Zhao Jiayong , Xia Shengli , Zhou Na , Ma Hui , Qiu Shaofu , Song Hongbin 
Published: July 2016

AbstractTo conduct the first comprehensive analysis of Shigella flexneri serotype 4s, a novel serotype found in 2010, we identified 24 serotype 4s isolates from 1973 shigellosis cases in China (2002–2014). The isolates were characterized by single nucleotide polymorphism (SNP) phylogenetic analysis, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine their genetic relatedness and analysed further for their antimicrobial susceptibilities and antimicrobial resistance determinants. The PFGE and SNP phylogenetic analyses suggest that S. flexneri serotype 4s strains are derived from multiple serotypes, including two predominant serotypes in China: serotype X variant and serotype II. Three new sequence types were identified by MLST. All isolates were resistant to ticarcillin, ampicillin and tetracycline, with high-level resistance to third-generation cephalosporins. Notably, all the isolates were multidrug resistant (MDR), with the highest levels of resistance observed for eight antimicrobials classes. Most isolates contain various antimicrobial resistance determinants. In conclusion, we found that serotype 4s isolates have multiple evolutionary sources, diverse biochemical characteristics and genomes and highly prevalent multidrug resistance and antimicrobial-resistant determinants. With few clinical treatment options, continuous monitoring and timely intervention against this emerging MDR serotype is essential. The possibility that serotype 4s will become the next predominant serotype exists.
Nanoscale imaging of untreated mammalian cells in a medium with low radiation damage using scanning electron-assisted dielectric microscopy
Authors: Okada Tomoko , Ogura Toshihiko 
Published: July 2016

AbstractImaging of untreated living cells in a medium at a nanometre-scale resolution under physiological conditions is a significant challenge. Scanning electron microscopy (SEM) is widely used to observe cells in various atmospheric holders or special equipment. However, untreated biological specimens in aqueous solution generally incur heavy radiation damage from the direct electron beam (EB); and these images exhibit very poor contrast. Therefore, a new method for generating high-contrast images of living cells under physiological conditions without radiation damage has been strongly desired. Here, we demonstrate the first nanoscale observation of living cultured mammalian cells using our newly developed scanning-electron assisted dielectric microscopy (SE-ADM) method with a culture dish holder. Using the difference in relative permittivity between water and specimens, our SE-ADM system aids in the visualisation of untreated biological samples in aqueous solution. In addition, specimens incurred only a low level of radiation damage because the tungsten (W)-coated silicon nitride (SiN) film absorbs irradiated electrons. Untreated cells and organelles are clearly visible in high-contrast and high-resolution images without staining and fixation. Furthermore, our method enables the detection of changes in organelle structures within cells via time-lapse imaging with minimal radiation damage.
Topological water wave states in a one-dimensional structure
Authors: Yang Zhaoju , Gao Fei , Zhang Baile 
Published: July 2016

AbstractTopological concepts have been introduced into electronic, photonic and phononic systems, but have not been studied in surface-water-wave systems. Here we study a one-dimensional periodic resonant surface-water-wave system and demonstrate its topological transition. By selecting three different water depths, we can construct different types of water waves - shallow, intermediate and deep water waves. The periodic surface-water-wave system consists of an array of cylindrical water tanks connected with narrow water channels. As the width of connecting channel varies, the band diagram undergoes a topological transition which can be further characterized by Zak phase. This topological transition holds true for shallow, intermediate and deep water waves. However, the interface state at the boundary separating two topologically distinct arrays of water tanks can exhibit different bands for shallow, intermediate and deep water waves. Our work studies for the first time topological properties of water wave systems and paves the way to potential management of water waves.
Characteristic distribution of finite-time Lyapunov exponents for chimera states
Authors: Botha André E. 
Published: July 2016

AbstractOur fascination with chimera states stems partially from the somewhat paradoxical, yet fundamental trait of identical, and identically coupled, oscillators to split into spatially separated, coherently and incoherently oscillating groups. While the list of systems for which various types of chimeras have already been detected continues to grow, there is a corresponding increase in the number of mathematical analyses aimed at elucidating the fundamental reasons for this surprising behaviour. Based on the model systems, there are strong indications that chimera states may generally be ubiquitous in naturally occurring systems containing large numbers of coupled oscillators – certain biological systems and high-Tc superconducting materials, for example. In this work we suggest a new way of detecting and characterising chimera states. Specifically, it is shown that the probability densities of finite-time Lyapunov exponents, corresponding to chimera states, have a definite characteristic shape. Such distributions could be used as signatures of chimera states, particularly in systems for which the phases of all the oscillators cannot be measured directly. For such cases, we suggest that chimera states could perhaps be detected by reconstructing the characteristic distribution via standard embedding techniques, thus making it possible to detect chimera states in systems where they could otherwise exist unnoticed.
Genome-wide analysis of HIF-2α chromatin binding sites under normoxia in human bronchial epithelial cells (BEAS-2B) suggests its diverse functions
Authors: Lee Meng-Chang , Huang Hsin-Ju , Chang Tzu-Hao , Huang Hsieh-Chou , Hsieh Shen-Yuan , Chen Yi-Siou , Chou Wei-Yuan , Chiang Chiao-Hsi , Lai Ching-Huang , Shiau Chia-Yang 
Published: July 2016

AbstractConstitutive functional HIF-2α was recently identified in cancer and stem cell lines under normoxia. In this study, BEAS-2B, a bronchial epithelial cell line, was shown to constitutively express active HIF-2α under normoxia and exhibit markers of pluripotency including Oct-4, Nanog and sphere formation. Oct-4 expression was reduced after knockdown of HIF-2α under normoxia. Global enrichment analysis of HIF-2α demonstrated the diverse functions of HIF-2α under normoxia. Bioinformatics analysis of the enriched loci revealed an enhancer role of HIF-2α binding sites, involvement of HIF-2α interacting proteins and enriched de novo motifs which suggest the diverse role of HIF-2α in pseudohypoxia. The low ratio of the discovered loci overlapping with those revealed in cancer cell lines 786-O (16.1%) and MCF-7 (15.9%) under hypoxia indicated a prevailing non-canonical mechanism. Hypoxia had positive, marginal or adverse effects on the enrichment of the selected loci in ChIP-PCR assays. Deletion of the N-terminal activation domain (N-TAD) of HIF-2α disrupted the reporting activity of two of the loci annotated to ELN and ANKRD31. Hypoxia incurring abundance variation of HIF-2α may misrepresent the N-TAD functions as canonical hypoxia inducible features via C-TAD activation. Elucidation of the pseudohypoxia functions of constitutive HIF-2α is useful for resolving its role in malignancy and pluripotency.
Molecular dynamics simulations of fcc-to-bcc transformation in pure iron: A review
Authors: Ou X. 
Published: July 2016

Molecular dynamics (MD) simulation has been used to study the martensitic transformation in iron at the atomic scale. The paper reviews the available interatomic interaction potentials for iron, which describe the properties of different phases present in that system. Cases on the fcc-to-bcc transformation in iron by MD simulations were included in the present paper. Factors affecting the fcc-to-bcc transformation in iron were analysed: (a) structural factors, such as grain/phase boundaries, grain sizes and stacking faults; (b) simulation conditions, such as the presence of free surfaces, external stress/strain and studied temperatures; (c) the interatomic interaction potential. The main emphasis of the present paper is on results giving insight on the mechanisms of the nucleation and growth of bcc phase in iron. This review was submitted as part of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged.
Insights into the physician assistant profession in Canada
Authors: Fréchette Danielle , Shrichand Arun 
Published: July 2016

ABSTRACT
Physician assistants (PAs) have been used for decades in the Canadian military. Now, PAs are being introduced in various clinical settings to provide patient care for the general population. This article reviews major developments in the PA profession across Canada over the last decade. Nearly 541 PAs are employed in Canada or work for a Canadian agency. Growing evidence demonstrates the positive effect of PAs; however, key issues challenge the extent to which the PA movement will continue to build momentum.
Which antidotes are available for the novel oral anticoagulants?
Authors: Thomas Rebekah , Gonzalez Renzo 
Published: July 2016

ABSTRACT
Use of novel (or target-specific) oral anticoagulants continues to increase. This article reviews idarucizumab and andexanet alfa, two antidotes that can be used to reverse anticoagulation in patients needing emergency surgery or with life-threatening bleeding.
PA and NP productivity in the Veterans Health Administration
Authors: Moran Eileen A. , Basa Edesha , Gao Jian , Woodmansee Denni , Almenoff Peter L. , Hooker Roderick S. 
Published: July 2016

ABSTRACT
This study assessed the 2014 clinical productivity of 5,959 physician assistants (PAs) and nurse practitioners (NPs) in the US Department of Veterans Affairs' Veterans Health Administration (VHA). Total work relative value units divided by the direct clinical full-time equivalent measured annual productivity, and correlated factors were examined using weighted analysis of variance. PAs and NPs in adult primary care roles were more productive than those in other specialties. Both providers were more productive in rural than in nonrural settings and less productive in teaching than nonteaching hospitals. Men were slightly more productive than women but age and years of VHA employment were not correlates of productivity. PAs were more productive when their scope of practice allowed significant autonomy; NP productivity was unaffected by supervisory requirements. PAs and NPs are an important component of the VHA provider workforce, and their productivity correlates with a number of factors. More organizational research is necessary to better understand the contributing roles PAs and NPs provide in a rapidly evolving, vertically integrated, national health delivery system.
Direct oral anticoagulants for venous thromboembolism treatment and prophylaxis
Authors: Yorkgitis Brian K. 
Published: July 2016

ABSTRACT
Direct oral anticoagulants are a popular option for prevention and treatment of venous thromboembolism. However, they possess significantly different pharmacologic properties from warfarin. This article reviews approved direct oral anticoagulants, their indications, pharmacologic properties, monitoring, and reversal strategies.
MICROBIOME MANIPULATION AND IMMUNE REGULATION
Authors: Garssen J. 
Published: July 2016

Our body is attacked continuously by many different danger signals. An effective immune system is essential in order to protect. Unbalanced immune reactivity seems to play a key role in non‐communicable diseases (NCDs) such as for example chronic pulmonary disease (COPD), allergies, asthma, diabetes, cancer and even cardiovascular diseases and obesity. According to the WHO NCDs are not only relevant for high income countries but even for middle and low income areas. It is essential to develop new avenues to prevent the enormous increase in incidence and severity of NCDs. Early life programming including proper education of our immune system (a.o. inflammation management) has been recognized as one of the most promising approaches.The awareness of the importance of a diverse microbiome in immune‐regulation/inflammation management and as a consequence impact on NCDs is growing exponentially. After birth, the development of a “healthy” gut microbiome is considered to play an important role in immune development and as a consequence inflammation management. The relevance of our microbiome in susceptibility for a.o. immune related diseases including NCDs is very well recognized nowadays. Non‐digestible prebiotic oligosaccharides and even some unique microbes are transferred by the mother through the breastmilk to the child. Some of these affect the composition and/or activity of the gastrointestinal microbiome leading to health benefits (prebiotic function). As an example it has been shown that specific non‐digestible oligosaccharides (GOS/FOS) induces a gut microbiome comparable at least in part to breastfed infants. In addition to indirect effects on the immune system via microbiome changes prebiotic oligosaccharides can affect immune cells in a direct fashion as well. Many research groups are currently in search for the unique receptors such as lectins/galectins that are responsible for these direct immune effects.Recent clinical trials indicated that unique prebiotic fibers can impair the incidence and severity of allergic disorders. The majority of the studies sofar indicated immune effects in individuals still having an immature immune system (infants and toddlers). However very recent data indicated significant impact on other immune related diseases in other life stages as well. Recent publications indicate significant effects on the immune system during HIV infections, cancer and asthma.Both pharma as well as specialized–nutrition companies do see the highly relevance of microbiome manupilation for both prevention as well as treatment of some immune related disorders linked to NCDs. However more research, multicenter trials, and longterm followup studies are needed in order to validate the uniqueness of a.o. non‐digestible oligosaccharides and microbiome management in both classical pharma approaches as well as specialised and medical nutrition aimed at NCD management.