bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximum palinstrophy amplification in the two-dimensional Navier–Stokes equations
Authors: Ayala Diego , Doering Charles R. , Simon Thilo M.
Published: January 2018

We derive and assess the sharpness of analytic upper bounds for the instantaneous growth rate and finite-time amplification of palinstrophy in solutions of the two-dimensional incompressible Navier–Stokes equations. A family of optimal solenoidal fields parametrized by initial values for the Reynolds number $Re$ and palinstrophy ${\mathcal{P}}$ which maximize $\text{d}{\mathcal{P}}/\text{d}t$ is constructed by numerically solving suitable optimization problems for a wide range of $Re$ and ${\mathcal{P}}$, providing numerical evidence for the sharpness of the analytic estimate $\text{d}{\mathcal{P}}/\text{d}t\leqslant (a+b\sqrt{\ln Re+c}){\mathcal{P}}^{3/2}$ with respect to both $Re$ and ${\mathcal{P}}$. This family of instantaneously optimal fields is then used as initial data in fully resolved direct numerical simulations, and the time evolution of different relevant norms is carefully monitored as the palinstrophy is transiently amplified before decaying. The peak values of the palinstrophy produced by these initial data, i.e. $\sup _{t>0}{\mathcal{P}}(t)$, are observed to scale with the magnitude of the initial palinstrophy ${\mathcal{P}}(0)$ in accord with the corresponding a priori estimate. Implications of these findings for the question of finite-time singularity formation in the three-dimensional incompressible Navier–Stokes equation are discussed.
Static rivulet instabilities: varicose and sinuous modes
Authors: Bostwick J. B. , Steen P. H.
Published: January 2018

A static rivulet is subject to disturbances in shape, velocity and pressure fields. Disturbances to interfacial shape accommodate a contact line that is either (i) fixed (pinned) or (ii) fully mobile (free) and preserves the static contact angle. The governing hydrodynamic equations for this inviscid, incompressible fluid are derived and then reduced to a functional eigenvalue problem on linear operators, which are parametrized by axial wavenumber and base-state volume. Solutions are decomposed according to their symmetry (varicose) or anti-symmetry (sinuous) about the vertical mid-plane. Dispersion relations are then computed. Static stability is obtained by setting growth rate to zero and recovers existing literature results. Critical growth rates and wavenumbers for the varicose and sinuous modes are reported. For the varicose mode, typical capillary break-up persists and the role of the liquid/solid interaction on the critical disturbance is illustrated. There exists a range of parameters for which the sinuous mode is the dominant instability mode. The sinuous instability mechanism is shown to correlate with horizontal centre-of-mass motion and illustrated using a toy model.
Twilight of Empire
Authors: Immerwahr Daniel
Published: January 2018

“The whole world knows that we covet no territory,” announced Herbert Hoover. Or was it Dwight Eisenhower who said that? (“The United States does not covet a single acre of land that belongs to another.”) Or perhaps John F. Kennedy (“This nation does not covet the territory of any people”), Lyndon Johnson (“We threaten no regime and covet no territory”), Gerald Ford (“America covets no one else's land”), or Ronald Reagan (“We Americans covet no foreign territory”)? The disavowing of territorial ambitions is a hallowed, bipartisan presidential tradition, like pardoning a turkey at Thanksgiving or hosting the annual Easter egg roll.
Radwa Ashour, African American Criticism, and the Production of Modern Arabic Literature
Authors: Dworkin Ira
Published: January 2018

In 1973, at the suggestion of her mentor Shirley Graham Du Bois, the Egyptian scholar, activist, teacher, and novelist Radwa Ashour enrolled at the University of Massachusetts, Amherst, to study African American literature and culture. Ashour’s 1975 dissertation “The Search for a Black Poetics: A Study of Afro-American Critical Writings,” along with her 1983 autobiography,Al-Rihla: Ayyam taliba misriyya fi amrika[The Journey: An Egyptian Woman Student’s Memoirs in America], specifically engage with debates that emerged at the First International Congress of Negro Writers and Artists in September 1956 between African Americans and others from the African diaspora (most notably Aimé Césaire) regarding the applicability of the “colonial thesis” to the United States. This article argues that Ashour’s early engagement with African American cultural politics are formative of her fiction, particularly her 1991 novel,Siraaj: An Arab Tale,which examines overlapping questions of slavery, empire, and colonialism in the Arab world.
Mental Disorders, Gender, and Partnership in Problem Alcohol Use Risk at Age 55+
Authors: Behrendt Silke , Bühringer Gerhard , Beesdo-Baum Katja , Strehle Jens , Jacobi Frank , Wittchen Hans-Ulrich
Published: January 2018

Abstract. Aim: To examine in subjects aged > = 55 years the association between preceding mental disorders (MD), gender, and partnership and past 12-month problematic alcohol use (PAU; daily drinking, binge drinking, drinking in excess of health guidelines). Methods: Based on a subsample aged > = 55 years of the nationally representative DEGS1-MH study (n = 2045/4483), we examined the association of single retrospectively assessed MD, gender, partnership, and latent risk profiles with subsequent 12-month PAU-outcomes using logistic regression and latent class analysis (LCA) with auxiliary variables. Results: Younger and male subjects, subjects with one vs. no MD, and those living with a partner had a higher PAU risk. In a four-class LCA-solution, two normative classes (45.5 %, 44.9 %) with low MD and high male respectively female gender probabilities, a “male-substance use disorder-depression”- (4.0 %) and a “female-internalizing”-class (5.5 %) were found. The male-normative and the “male-substance use disorder”-class were associated with a higher PAU risk, including drinking in excess of different health guidelines (p < 0.05). Conclusions: The large group of male individuals with low MD probabilities may be relevant for predicting critical alcohol use behaviors in middle and older adulthood and may profit from low-threshold general preventive measures, while the smaller male group with elevated lifetime substance use disorder and depression risk may profit from targeted clinical interventions.
A randomised study in young subjects of the effects of eating extra fruit or nuts on periodontal inflammation
Authors: Fridell Sara , Ström Edvin , Agebratt Christian , Leanderson Per , Guldbrand Hans , Nystrom Fredrik H
Published: January 2018

Objectives/Aims:

Fruit is often advocated as a healthy source of nutrients and vitamins. However, the high contents of sugars in many fruits could potentially counteract positive effects on the teeth.

Materials and methods:

We recruited 30 healthy non-obese participants who were randomised to either supplement their diet with extra fruits or nuts, each at +7 kcal/kg body weight/day, for 2 months.

Results:

Fructose intake increased from 9.1±6.0 to 25.6±9.6 g/day, P<0.0001, in the fruit group and was reduced from 12.4±5.7 to 6.5±5.3 g/day, P=0.007, in the nut group. Serum-vitamin C increased in both groups (fruit: P=0.017; nuts: P=0.009). α-Tocopherol/cholesterol ratio increased in the fruit group (P=0.0033) while β-carotene/cholesterol decreased in the nut group (P<0.0001). The amount of subjects with probing pocket depths ⩾4 mm in the fruit group was reduced (P=0.045) according to blinded examinations, and the difference in the changes in probing pockets ⩾4 mm was also statistically significant between the food groups (P=0.010).

Conclusion:

A large increase of fruit intake, compared with nuts, had a favourable effect on periodontal status in some respects, despite the high sugar contents. To search for potential protective micronutrients in fruit that protect the teeth could be an aim for further research.
EGBMMDA: Extreme Gradient Boosting Machine for MiRNA-Disease Association prediction
Authors: Chen Xing , Huang Li , Xie Di , Zhao Qi
Published: January 2018

Associations between microRNAs (miRNAs) and human diseases have been identified by increasing studies and discovering new ones is an ongoing process in medical laboratories. To improve experiment productivity, researchers computationally infer potential associations from biological data, selecting the most promising candidates for experimental verification. Predicting potential miRNA–disease association has become a research area of growing importance. This paper presents a model of Extreme Gradient Boosting Machine for MiRNA-Disease Association (EGBMMDA) prediction by integrating the miRNA functional similarity, the disease semantic similarity, and known miRNA–disease associations. The statistical measures, graph theoretical measures, and matrix factorization results for each miRNA-disease pair were calculated and used to form an informative feature vector. The vector for known associated pairs obtained from the HMDD v2.0 database was used to train a regression tree under the gradient boosting framework. EGBMMDA was the first decision tree learning-based model used for predicting miRNA–disease associations. Respectively, AUCs of 0.9123 and 0.8221 in global and local leave-one-out cross-validation proved the model’s reliable performance. Moreover, the 0.9048 ± 0.0012 AUC in fivefold cross-validation confirmed its stability. We carried out three different types of case studies of predicting potential miRNAs related to Colon Neoplasms, Lymphoma, Prostate Neoplasms, Breast Neoplasms, and Esophageal Neoplasms. The results indicated that, respectively, 98%, 90%, 98%, 100%, and 98% of the top 50 predictions for the five diseases were confirmed by experiments. Therefore, EGBMMDA appears to be a useful computational resource for miRNA–disease association prediction.
Publisher Correction: Causes of model dry and warm bias over central U.S. and impact on climate projections
Authors: Lin Yanluan , Dong Wenhao , Zhang Minghua , Xie Yuanyu , Xue Wei , Huang Jianbin , Luo Yong
Published: January 2018

The original version of this Article contained an error in Figure 2. In panel a, the x axis of the graph was incorrectly labeled ‘precipitation bias’, and should have read ‘negative precipitation bias’. This error has been corrected in both the PDF and HTML versions of the Article.
Magnetically induced transparency of a quantum metamaterial composed of twin flux qubits
Authors: Shulga K. V. , Il’ichev E. , Fistul M. V. , Besedin I. S. , Butz S. , Astafiev O. V. , Hübner U. , Ustinov A. V.
Published: January 2018

Quantum theory is expected to govern the electromagnetic properties of a quantum metamaterial, an artificially fabricated medium composed of many quantum objects acting as artificial atoms. Propagation of electromagnetic waves through such a medium is accompanied by excitations of intrinsic quantum transitions within individual meta-atoms and modes corresponding to the interactions between them. Here we demonstrate an experiment in which an array of double-loop type superconducting flux qubits is embedded into a microwave transmission line. We observe that in a broad frequency range the transmission coefficient through the metamaterial periodically depends on externally applied magnetic field. Field-controlled switching of the ground state of the meta-atoms induces a large suppression of the transmission. Moreover, the excitation of meta-atoms in the array leads to a large resonant enhancement of the transmission. We anticipate possible applications of the observed frequency-tunable transparency in superconducting quantum networks.
A robust targeted sequencing approach for low input and variable quality DNA from clinical samples
Authors: So Austin P. , Vilborg Anna , Bouhlal Yosr , Koehler Ryan T. , Grimes Susan M. , Pouliot Yannick , Mendoza Daniel , Ziegle Janet , Stein Jason , Goodsaid Federico , Lucero Michael Y. , De La Vega Francisco M. , Ji Hanlee P.
Published: January 2018

Next-generation deep sequencing of gene panels is being adopted as a diagnostic test to identify actionable mutations in cancer patient samples. However, clinical samples, such as formalin-fixed, paraffin-embedded specimens, frequently provide low quantities of degraded, poor quality DNA. To overcome these issues, many sequencing assays rely on extensive PCR amplification leading to an accumulation of bias and artifacts. Thus, there is a need for a targeted sequencing assay that performs well with DNA of low quality and quantity without relying on extensive PCR amplification. We evaluate the performance of a targeted sequencing assay based on Oligonucleotide Selective Sequencing, which permits the enrichment of genes and regions of interest and the identification of sequence variants from low amounts of damaged DNA. This assay utilizes a repair process adapted to clinical FFPE samples, followed by adaptor ligation to single stranded DNA and a primer-based capture technique. Our approach generates sequence libraries of high fidelity with reduced reliance on extensive PCR amplification—this facilitates the accurate assessment of copy number alterations in addition to delivering accurate single nucleotide variant and insertion/deletion detection. We apply this method to capture and sequence the exons of a panel of 130 cancer-related genes, from which we obtain high read coverage uniformity across the targeted regions at starting input DNA amounts as low as 10 ng per sample. We demonstrate the performance using a series of reference DNA samples, and by identifying sequence variants in DNA from matched clinical samples originating from different tissue types.
Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation
Authors: Zanello Susana B. , Tadigotla Vasisht , Hurley James , Skog Johan , Stevens Brian , Calvillo Eusebia , Bershad Eric
Published: January 2018

The visual impairment and intracranial pressure (VIIP) syndrome is a neuro–ophthalmologic condition described in astronauts returning from long duration space missions. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is characterized by a chronic elevation of intracranial pressure (ICP) in the absence of an intracranial mass lesion. Because VIIP and IIH share some neurologic and ophthalmologic manifestations, the latter might be used as a model to study some of the processes underlying VIIP. This work constitutes a preliminary investigation of the molecular pathways associated with the elevation of ICP in IIH. Gene expression signatures were obtained from exosomes collected from CSF and plasma in patients with possible signs of IIH. The gene expression targets focused on inflammatory genes and miRNAs. The results suggest that inflammatory cytokine-driven processes and immune cell migration are activated when ICP is elevated in IIH patients, either as a cause or effect of the ICP increase. Several miRNAs appear to be involved in this response, among which miR-9 and miR-16 are upregulated in CSF and plasma of higher ICP subjects. This study provides evidence in support of neurophysiological alterations and neuro-immunomodulation in this condition. If similar changes are seen in astronauts manifesting with the VIIP syndrome, an underlying pathophysiological basis may be discovered.
Majorana zero modes and long range edge correlation in interacting Kitaev chains: analytic solutions and density-matrix-renormalization-group study
Authors: Miao Jian-Jian , Jin Hui-Ke , Zhang Fu-Chun , Zhou Yi
Published: January 2018

We study Kitaev model in one-dimension with open boundary condition by using exact analytic methods for non-interacting system at zero chemical potential as well as in the symmetric case of Δ = t, and by using density-matrix-renormalization-group method for interacting system with nearest neighbor repulsion interaction. We suggest and examine an edge correlation function of Majorana fermions to characterize the long range order in the topological superconducting states and study the phase diagram of the interating Kitaev chain.
The effect of image position on the Independent Components of natural binocular images
Authors: Hunter David W. , Hibbard Paul B.
Published: January 2018

Human visual performance degrades substantially as the angular distance from the fovea increases. This decrease in performance is found for both binocular and monocular vision. Although analysis of the statistics of natural images has provided significant insights into human visual processing, little research has focused on the statistical content of binocular images at eccentric angles. We applied Independent Component Analysis to rectangular image patches cut from locations within binocular images corresponding to different degrees of eccentricity. The distribution of components learned from the varying locations was examined to determine how these distributions varied across eccentricity. We found a general trend towards a broader spread of horizontal and vertical position disparity tunings in eccentric regions compared to the fovea, with the horizontal spread more pronounced than the vertical spread. Eccentric locations above the centroid show a strong bias towards far-tuned components, eccentric locations below the centroid show a strong bias towards near-tuned components. These distributions exhibit substantial similarities with physiological measurements in V1, however in common with previous research we also observe important differences, in particular distributions of binocular phase disparity which do not match physiology.
Stratification-induced reorientation of disk settling through ambient density transition
Authors: Mrokowska Magdalena M.
Published: January 2018

Settling due to gravity force is a basic transport mechanism of solid particles in fluids in the Earth. A large portion of particles occurring in nature and used in technical applications are non-spherical. Settling of particles is usually studied in homogeneous ambient conditions, however, stratification is inherent of natural fluids. It has been acknowledged that stratification modifies the velocity of settling spheres and amorphous aggregates. However, the effect of particle shape on the dynamics of settling through density-stratified ambient fluid has not been recognized well enough. Here I show experimental evidence that continuous density transition markedly modifies the settling dynamics of a disk in terms of settling velocity and orientation of a particle. Settling dynamics of a disk are more complex than dynamics of spheres and aggregates studied previously. I found that in a two-layer ambient with density transition, a disk settling in a low Reynolds number regime undergoes five phases of settling with the orientation varying from horizontal to vertical, and it may achieve two local minimum settling velocities in the density transition layer. Moreover, I found that the settling dynamics depends on a density difference between upper and lower homogeneous layers, stratification strength and thickness of density transition.
Reference gene identification and validation for quantitative real-time PCR studies in developing Xenopus laevis
Authors: Mughal Bilal B. , Leemans Michelle , Spirhanzlova Petra , Demeneix Barbara , Fini Jean-Baptiste
Published: January 2018

Reference genes are essential for gene expression analysis when using real-time quantitative PCR (RT-qPCR). Xenopus laevis is a popular amphibian model for studying vertebrate embryogenesis and development. Further, X. laevis is ideal for studying thyroid signaling due to its thyroid dependent metamorphosis, a stage comparable to birth in humans. When using PCR based studies, a primary concern is the choice of reference genes. Commonly used references are eef1a1, odc1, rpl8, and actnB, although there is a lack of ad hoc reference genes for X. laevis. Here, we used previously published RNA-seq data on different X. laevis stages and identified the top 14 candidate genes with respect to their expression levels as a function of developmental stage and degree of variation. We further evaluated the stability of these and other candidate genes using RT-qPCR on various stages including the unfertilised eggs, whole embryos during early development and brains during late development. We used four different statistical software packages: deltaCT, geNorm, NormFinder and BestKeeper. We report optimized reference gene pair combinations for studying development (early whole embryos), brains at later stages (metamorphosis and adult), and  thyroid signalling. These reference gene pairs are suitable for studying different aspects of X. laevis development and organogenesis.
Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells
Authors: Montaner Aneley , da Silva Santana Themis Taynah , Schroeder Timm , Einicker-Lamas Marcelo , Girardini Javier , Costa Marcos Romualdo , Banchio Claudia
Published: January 2018

Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.
Engineered 3D-printed artificial axons
Authors: Espinosa-Hoyos Daniela , Jagielska Anna , Homan Kimberly A. , Du Huifeng , Busbee Travis , Anderson Daniel G. , Fang Nicholas X. , Lewis Jennifer A. , Van Vliet Krystyn J.
Published: January 2018

Myelination is critical for transduction of neuronal signals, neuron survival and normal function of the nervous system. Myelin disorders account for many debilitating neurological diseases such as multiple sclerosis and leukodystrophies. The lack of experimental models and tools to observe and manipulate this process in vitro has constrained progress in understanding and promoting myelination, and ultimately developing effective remyelination therapies. To address this problem, we developed synthetic mimics of neuronal axons, representing key geometric, mechanical, and surface chemistry components of biological axons. These artificial axons exhibit low mechanical stiffness approaching that of a human axon, over unsupported spans that facilitate engagement and wrapping by glial cells, to enable study of myelination in environments reflecting mechanical cues that neurons present in vivo. Our 3D printing approach provides the capacity to vary independently the complex features of the artificial axons that can reflect specific states of development, disease, or injury. Here, we demonstrate that oligodendrocytes’ production and wrapping of myelin depend on artificial axon stiffness, diameter, and ligand coating. This biofidelic platform provides direct visualization and quantification of myelin formation and myelinating cells’ response to both physical cues and pharmacological agents.
Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters
Authors: Ito Kenyu , Ohkawara Bisei , Yagi Hideki , Nakashima Hiroaki , Tsushima Mikito , Ota Kyotaro , Konishi Hiroyuki , Masuda Akio , Imagama Shiro , Kiyama Hiroshi , Ishiguro Naoki , Ohno Kinji
Published: January 2018

FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18−/− mice at E18.5 showed decreased expressions of the NMJ-specific Chrne and Colq genes in the diaphragm. In Fgf18−/− diaphragms, the synaptophysin-positive areas at the nerve terminals and the acetylcholine receptor (AChR)-positive areas at the motor endplates were both approximately one-third of those in wild-type embryos. Fgf18−/− diaphragms ultrastructurally showed abnormal aggregation of multiple nerve terminals making a gigantic presynapse with sparse synaptic vesicles, and simplified motor endplates. In Fgf18−/− diaphragms, miniature endplate potentials were low in amplitude with markedly reduced frequency. In C2C12 myotubes, FGF18 enhanced AChR clustering, which was blocked by inhibiting FGFRs or MEK1. We propose that FGF18 plays a pivotal role in AChR clustering and NMJ formation in mouse embryogenesis.
Variations in bacterial and archaeal communities along depth profiles of Alaskan soil cores
Authors: Tripathi Binu Mani , Kim Mincheol , Kim Yongwon , Byun Eunji , Yang Ji-Woong , Ahn Jinho , Lee Yoo Kyung
Published: January 2018

Understating the microbial communities and ecological processes that influence their structure in permafrost soils is crucial for predicting the consequences of climate change. In this study we investigated the bacterial and archaeal communities along depth profiles of four soil cores collected across Alaska. The bacterial and archaeal diversity (amplicon sequencing) overall decreased along the soil depth but the depth-wise pattern of their abundances (qPCR) varied by sites. The community structure of bacteria and archaea displayed site-specific pattern, with a greater role of soil geochemical characteristics rather than soil depth. In particular, we found significant positive correlations between methane trapped in cores and relative abundance of methanogenic archaeal genera, indicating a strong association between microbial activity and methane production in subsurface soils. We observed that bacterial phylogenetic community assembly tended to be more clustered in surface soils than in deeper soils. Analyses of phylogenetic community turnover among depth profiles across cores indicated that the relative influence of deterministic and stochastic processes was mainly determined by soil properties rather than depth. Overall, our findings emphasize that the vertical distributions of bacterial and archaeal communities in permafrost soils are to a large extent determined by the variation in site-specific soil properties.
Climate change risk to forests in China associated with warming
Authors: Yin Yunhe , Ma Danyang , Wu Shaohong
Published: January 2018

Variations in forest net primary productivity (NPP) reflects the combined effects of key climate variables on ecosystem structure and function, especially on the carbon cycle. We performed risk analysis indicated by the magnitude of future negative anomalies in NPP in comparison with the natural interannual variability to investigate the impact of future climatic projections on forests in China. Results from the multi-model ensemble showed that climate change risk of decreases in forest NPP would be more significant in higher emission scenario in China. Under relatively low emission scenarios, the total area of risk was predicted to decline, while for RCP8.5, it was predicted to first decrease and then increase after the middle of 21st century. The rapid temperature increases predicted under the RCP8.5 scenario would be probably unfavorable for forest vegetation growth in the long term. High-level risk area was likely to increase except RCP2.6. The percentage area at high risk was predicted to increase from 5.39% (2021–2050) to 27.62% (2071–2099) under RCP8.5. Climate change risk to forests was mostly concentrated in southern subtropical and tropical regions, generally significant under high emission scenario of RCP8.5, which was mainly attributed to the intensified dryness in south China.
Adipose-specific lipin1 overexpression in mice protects against alcohol-induced liver injury
Authors: Zhang Wenliang , Zhong Wei , Sun Qian , Sun Xinguo , Zhou Zhanxiang
Published: January 2018

Excessive fatty acid release from the white adipose tissue (WAT) contributes to the development of alcoholic liver disease (ALD). Lipin1 (LPIN1), as a co-regulator of DNA-bound transcription factors and a phosphatidic acid (PA) phosphatase (PAP) enzyme that dephosphorylates PA to form diacylglycerol (DAG), is dramatically reduced by alcohol in the WAT. This study aimed at determining the role of adipose LPIN1 in alcohol-induced lipodystrophy and the development of ALD. Transgenic mice overexpressing LPIN1 in adipose tissue (LPIN1-Tg) and wild type (WT) mice were fed a Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks. Alcohol feeding to WT mice resulted in significant liver damage, which was significantly alleviated in the LPIN1-Tg mice. Alcohol feeding significantly reduced epididymal WAT (EWAT) mass, inhibited lipogenesis, and increased lipolysis in WT mice, which were attenuated in the LPIN1-Tg mice. LPIN1 overexpression also partially reversed alcohol-reduced plasma leptin levels. In WT mice, alcohol feeding induced hepatic lipid accumulation and down-regulation of beta-oxidation genes, which were dramatically alleviated in the LPIN1-Tg mice. LPIN1 overexpression also significantly attenuated alcohol-induced hepatic ER stress. These results suggest that overexpression of LPIN1 in adipose tissue restores WAT lipid storage function and secretive function to alleviate alcohol-induced liver injury.
Reconstruction of the domain orientation distribution function of polycrystalline PZT ceramics using vector piezoresponse force microscopy
Authors: Kratzer Markus , Lasnik Michael , Röhrig Sören , Teichert Christian , Deluca Marco
Published: January 2018

Lead zirconate titanate (PZT) is one of the prominent materials used in polycrystalline piezoelectric devices. Since the ferroelectric domain orientation is the most important parameter affecting the electromechanical performance, analyzing the domain orientation distribution is of great importance for the development and understanding of improved piezoceramic devices. Here, vector piezoresponse force microscopy (vector-PFM) has been applied in order to reconstruct the ferroelectric domain orientation distribution function of polished sections of device-ready polycrystalline lead zirconate titanate (PZT) material. A measurement procedure and a computer program based on the software Mathematica have been developed to automatically evaluate the vector-PFM data for reconstructing the domain orientation function. The method is tested on differently in-plane and out-of-plane poled PZT samples, and the results reveal the expected domain patterns and allow determination of the polarization orientation distribution function at high accuracy.
Unveiling the piezoelectric nature of polar α-phase P(VDF-TrFE) at quasi-two-dimensional limit
Authors: Qian Jun , Jiang Sai , Wang Qijing , Zheng Shushu , Guo Shuya , Yi Chang , Wang Jianpu , Wang Xinran , Tsukagoshi Kazuhito , Shi Yi , Li Yun
Published: January 2018

Piezoelectric response of P(VDF-TrFE), which is modulated by the dipole density due to the polarization switching on applying an electric field, allows it act as the fundamental components for electromechanical systems. As proposed since the 1970s, its polar α-phase is supposed to yield an enhanced piezoelectric activity. However, its experimental verification has never been reported, hampered by a substantial challenge for the achievement of a smooth, neat α-phase film. Here, we prepare ultrathin crystalline α-phase P(VDF-TrFE) films on the AlOx/Al-coated SiO2/Si substrates via a solution-based approach at room temperature. Thus, we unveil the piezoelectric nature of the polar α-phase P(VDF-TrFE) at a quasi-two-dimensional limit. The obtained values of the relative morphological deformation, the local effective piezoelectric coefficient, and the electric field-induced strain reach up to 37 pm, −46.4 pm V−1, and 4.1%, respectively. Such a robust piezoelectric response is even higher than that of the β-phase. Besides, the evolution of piezoelectricity, which is related to the piezoelectric properties of two polarization states, is also studied. Our work can enable the exploration of the prospective applications of polar α-phase P(VDF-TrFE) films.
Biogenesis of podosome rosettes through fission
Authors: Kuo Szu-Lin , Chen Chien-Lin , Pan Yi-Ru , Chiu Wen-Tai , Chen Hong-Chen
Published: January 2018

Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts. Fission is a more efficient way than de novo assembly to generate new podosome rosettes in these cells. Podosome rosettes undergoing fission possess higher motility and a stronger matrix-degrading capability. Podosome rosette fission may be the result of polarized myosin II-mediated contractility of these structures, which is coordinately regulated by myosin light chain kinase and Rho-associated kinase II. Collectively, this study unveils a previously unknown mechanism—fission for the biogenesis of podosome rosettes.
Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials
Authors: Balasubramanian Preetha , Williams Constance , Shapiro Mariya B. , Sinangil Faruk , Higgins Keith , Nádas Arthur , Totrov Maxim , Kong Xiang-Peng , Fiore-Gartland Andrew J. , Haigwood Nancy L. , Zolla-Pazner Susan , Hioe Catarina E.
Published: January 2018

Immunization with HIV AIDSVAX gp120 vaccines in the phase III VAX003 and VAX004 trials did not confer protection. To understand the shortcomings in antibody (Ab) responses induced by these vaccines, we evaluated the kinetics of Ab responses to the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral functions during the course of 7 vaccinations over a 30.5-month period. Plasma samples from VAX003 and VAX004 vaccinees and placebo recipients were measured for ELISA-binding Abs and for virus neutralization, Ab-dependent cellular phagocytosis (ADCP), and Ab-dependent cellular cytotoxicity (ADCC). Ab responses to V1V2 and V3 peaked after 3 to 4 immunizations and declined after 5 to 7 immunizations. The deteriorating responses were most evident against epitopes in the underside of the V1V2 β-barrel and in the V3 crown. Correspondingly, vaccinees demonstrated higher neutralization against SF162 pseudovirus sensitive to anti-V1V2 and anti-V3 Abs after 3 or 4 immunizations than after 7 immunizations. Higher levels of ADCP and ADCC were also observed at early or mid-time points as compared with the final time point. Hence, VAX003 and VAX004 vaccinees generated V1V2- and V3-binding Abs and functional Abs after 3 to 4 immunizations, but subsequent boosts did not maintain these responses.
Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury
Authors: Ruppert Katherine A. , Nguyen Tin T. , Prabhakara Karthik S. , Toledano Furman Naama E. , Srivastava Amit K. , Harting Matthew T. , Cox Charles S. , Olson Scott D.
Published: January 2018

No current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs). In this study, we investigate whether systemic administration of EVs isolated from human MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based therapy for SCI. Additionally, we investigate whether EVs isolated from human MSCs stimulated with pro-inflammatory cytokines have enhanced anti-inflammatory effects when administered after SCI. Immunohistochemistry supported the quantitative analysis, demonstrating a diminished inflammatory response with apparent astrocyte and microglia disorganization in cord tissue up to 10 mm caudal to the injury site. Locomotor recovery scores showed significant improvement among animals treated with MSCEv. Significant increases in mechanical sensitivity threshold were observed in animals treated with EVs from either naïve MSC (MSCEvwt) or stimulated MSC (MSCEv+), with a statistically significant increase in threshold for MSCEv+-treated animals when compared to those that received MSCEvwt. In conclusion, these data show that treatment of acute SCI with extracellular vesicles derived from human MSCs attenuates neuroinflammation and improves functional recovery.
Neoadjuvant therapy in relation to lymphadenectomy and resection margins during surgery for oesophageal cancer
Authors: Kauppila Joonas H. , Wahlin Karl , Lagergren Pernilla , Lagergren Jesper
Published: January 2018

Differences in lymph node yield and tumour-involved resection margins comparing neoadjuvant therapy plus surgery with surgery alone for oesophageal cancer are unclear. Patients who underwent oesophageal cancer surgery in Sweden in 1987–2010 were included. Patients treated with neoadjuvant therapy were compared with those who underwent surgery alone. Outcomes were the number of examined lymph nodes (main outcome), number metastatic lymph nodes, and resection margin status. Rate ratios (RRs) and 95% CIs of lymph node yield were calculated by Poisson regression, and odds ratios (ORs) and 95% CIs of resection margin status by multivariable logistic regression, both adjusted for confounders. Among 1818 patients, 587 (32%) had received neoadjuvant therapy and 1231 (68%) had not. Lymph node yield was lower in the neoadjuvant therapy group (median 6 versus 8; adjusted RR 0.75, 0.73–0.78). Fewer metastatic nodes were identified following neoadjuvant therapy (median 0 versus 1; adjusted RR 0.76, 0.69–0.84). Neoadjuvant therapy associated to decreased risk of tumour-involved resection margins when adjusted for confounders except T-stage (OR 0.52, 0.38–0.70), but the association did not remain after adjustment for T-stage (OR 0.91, 0.64–1.29). Neoadjuvant therapy seems to decrease the lymph node yield and decrease the risk of tumour-involved resection margins by shrinking primary tumour.
Leakage correction improves prognosis prediction of dynamic susceptibility contrast perfusion MRI in primary central nervous system lymphoma
Authors: Kim Yeon Soo , Choi Seung Hong , Yoo Roh-Eul , Kang Koung Mi , Yun Tae Jin , Kim Ji-hoon , Sohn Chul-Ho , Park Sung-Hye , Won Jae-Kyung , Kim Tae Min , Park Chul-Kee , Kim Il Han
Published: January 2018

To evaluate whether the cerebral blood volume (CBV) measurement with leakage correction from dynamic susceptibility contrast perfusion weighted imaging can be useful in predicting prognosis for primary central nervous system lymphoma (PCNSL). 46 PCNSL patients were included and classified by radiation therapy (RT) stratification into RT (n = 30) and non-RT (n = 16) groups. The corresponding histogram parameters of normalized CBV (nCBV) maps with or without leakage correction were calculated on contrast-enhanced T1 weighted image (CE T1WI) or on fluid attenuated inversion recovery image. The 75th percentile nCBV with leakage correction based on CE T1WI (T1 nCBVL75%) had a significant difference between the short and long progression free survival (PFS) subgroups of the RT group and the non-RT group, respectively. Based on the survival analysis, patients in the RT group with high T1 nCBVL75% had earlier progression than the others with a low T1 nCBVL75%. However, patients in the non-RT group with a high T1 nCBVL75% had slower progression than the others with a low T1 nCBVL75%. Based on RT stratification, the CBV with leakage correction has potential as a noninvasive biomarker for the prognosis prediction of PCNSL to identify high risk patients and it has a different correlation with the PFS based on the presence of combined RT.
A biofilm and organomineralisation model for the growth and limiting size of ooids
Authors: Batchelor Murray T. , Burne Robert V. , Henry Bruce I. , Li Fei , Paul Josef
Published: January 2018

Ooids are typically spherical sediment grains characterised by concentric layers encapsulating a core. There is no universally accepted explanation for ooid genesis, though factors such as agitation, abiotic and/or microbial mineralisation and size limitation have been variously invoked. Here we examine the possible influence of microbial organomineralisation on the formation of some naturally occurring ooids. We develop a mathematical model for ooid growth, inspired by work on avascular brain tumours, that assumes mineralisation in a biofilm to form a central core which then nucleates the progressive growth of concentric laminations. The model predicts a limiting size with the sequential width variation of growth rings comparing favourably with those observed in experimentally grown ooids generated from biomicrospheres. In reality, this model pattern may be complicated during growth by syngenetic aggrading neomorphism of the unstable mineral phase, followed by diagenetic recrystallisation that further complicates the structure. Our model provides a potential key to understanding the genetic archive preserved in the internal structures of some ooids.
Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo
Authors: Lee Ying-Ray , Kuo Szu-Han , Lin Ching-Yen , Fu Po-Jung , Lin Yee-Shin , Yeh Trai-Ming , Liu Hsiao-Sheng
Published: January 2018

Dengue virus (DENV) utilizes the endoplasmic reticulum (ER) for replication and assembling. Accumulation of unfolded proteins in the ER lumen leads to ER stress and unfolded protein response (UPR). Three branches of UPRs temporally modulated DENV infection. Moreover, ER stress can also induce autophagy. DENV infection induces autophagy which plays a promotive role in viral replication has been reported. However, the role of ER stress in DENV-induced autophagy, viral titer, and pathogenesis remain unclear. Here, we reveal that ER stress and its downstream UPRs are indispensable for DENV-induced autophagy in various human cells. We demonstrate that PERK-eIF2α and IRE1α-JNK signaling pathways increased autophagy and viral load after DENV infection. However, ATF6-related pathway showed no effect on autophagy and viral replication. IRE1α-JNK downstream molecule Bcl-2 was phosphorylated by activated JNK and dissociated from Beclin 1, which playing a critical role in autophagy activation. These findings were confirmed as decreased viral titer, attenuated disease symptoms, and prolonged survival rate in the presence of JNK inhibitor in vivo. In summary, we are the first to reveal that DENV2-induced ER stress increases autophagy activity, DENV replication, and pathogenesis through two UPR signaling pathways both in vitro and in vivo.
Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In Neurologically Asymtomatic Patients
Authors: Barcellini Wilma , Scola Elisa , Lanfranconi Silvia , Grottaroli Marika , Binda Francesca , Fattizzo Bruno , Zaninoni Anna , Valcamonica Gloria , Cinnante Claudia Maria , Boschetti Carla , Buoli Massimiliano , Altamura Carlo Alfredo , Bresolin Nereo , Triulzi Fabio , Zanella Alberto , Cortelezzi Agostino
Published: January 2018

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged <65) showed pathological findings: 9 white matter (WM) abnormalities related to chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement.
Electromagnetic Radiation Disturbed the Photosynthesis of Microcystis aeruginosa at the Proteomics Level
Authors: Tang Chao , Yang Chuanjun , Yu Hui , Tian Shen , Huang Xiaomei , Wang Weiyi , Cai Peng
Published: January 2018

Photosynthesis of Microcystis aeruginosa under Electromagnetic Radiation (1.8 GHz, 40 V/m) was studied by using the proteomics. A total of 30 differentially expressed proteins, including 15 up-regulated and 15 down-regulated proteins, were obtained in this study. The differentially expressed proteins were significantly enriched in the photosynthesis pathway, in which the protein expression levels of photosystems II cytochrome b559 α subunit, cytochrome C550, PsbY, and F-type ATP synthase (a, b) decreased. Our results indicated that electromagnetic radiation altered the photosynthesis-related protein expression levels, and aimed at the function of photosynthetic pigments, photosystems II potential activity, photosynthetic electron transport process, and photosynthetic phosphorylation process of M. aeruginosa. Based on the above evidence, that photoreaction system may be deduced as a target of electromagnetic radiation on the photosynthesis in cyanobacteria; the photoreaction system of cyanobacteria is a hypothetical “shared target effector” that responds to light and electromagnetic radiation; moreover, electromagnetic radiation does not act on the functional proteins themselves but their expression processes.