bluuebunny/crossref_metadata_2025 huggingface dataset:
Techniques of Ectopic Reservoir Placement and Their Pitfalls
Authors: Thirumavalavan Nannan , Gross Martin S. , Munarriz Ricardo
Published: October 2017

Background

Ectopic placement of penile prosthesis reservoirs has become more common in patients whose space of Retzius has been compromised.

Aim

To describe techniques and instruments used to place penile prosthesis reservoirs ectopically.

Methods

We present our method of placing ectopic reservoirs and review the literature for other techniques. We also catalog the instruments used for this purpose.

Outcomes

Similar to traditional reservoir placement, successful ectopic reservoir implantation requires good cosmetic and functional success and low complication rates.

Results

Ectopic reservoir placement has been shown to be effective, to safely avoid bowel, bladder, and vascular injury, and to maintain excellent function and cosmesis. Multiple tools for ectopic placement have been described, but no data exist comparing their effectiveness and complications. Examples include dissection of the space anterior to the transversalis muscle using the surgeon's finger, a pediatric Yankauer suction tip, or a Foerster lung clamp. Instruments described to grasp and advance the reservoir include a sponge stick, a Foerster lung clamp, and the ectopic reservoir insertion tool (Sontec, Centennial, CO, USA). The effect of different instruments on the integrity of reservoir has not been extensively studied.

Clinical Implications

Attention to technique and the instruments used to dissect the ectopic space and grasp the reservoir are crucial to successful ectopic reservoir placement.

Strengths and Limitations

Reports of vascular, bowel, or bladder injuries during ectopic placement are exceedingly rare, as are reports of injury to reservoirs caused by traumatic grasping. However, no methods or tools have been compared in head-to-head trials.

Conclusion

Ectopic placement is safe and effective, but differences between methods and instruments have not been delineated.
Transport properties of warm and hot dense iron from orbital free and corrected Yukawa potential molecular dynamics
Authors: Sun H.Y. , Kang Dongdong , Hou Yong , Dai J.Y.
Published: October 2017

The equation of states, diffusions, and viscosities of strongly coupled Fe at 80 and 240 eV with densities from 1.6 to 40 g/cm3 are studied by orbital-free molecular dynamics, classical molecular dynamics with a corrected Yukawa potential and compared with the results from average atom model. A new local pseudopotential is generated for orbital free calculations. For low densities, the Yukawa model captures the correct ionic interaction behavior around the first peak of the radial distribution function (RDF), thus it gives correct RDFs and transport coefficients. For higher densities, the scaled transformation of the Yukawa potential or adding a short range repulsion part to the Yukawa potential can give correct RDFs and transport coefficients. The corrected potentials are further validated by the force matching method.
Pulmonary Rehabilitation in a Patient With Bronchiectasis and Underlying Cerebral Palsy: A Case Presentation
Authors: Yoon Seo Yeon , Kim Yong Wook , Choi Ja Young
Published: October 2017

Bronchiectasis is a chronic pulmonary disease characterized by the permanent dilatation of the airways, with recurrent infections. As the disease progresses, extrapulmonary symptoms manifest. If the patient with bronchiectasis has an underlying central nervous system disease such as cerebral palsy (CP), extrapulmonary functions decline faster. The co‐occurrence of these 2 diseases may make care more complex, and there have been no reports about pulmonary rehabilitation (PR) in this class of patients. Here, we present a patient with bronchiectasis and underlying CP who showed marked improvement of pulmonary function and clinical symptoms after 6 weeks of a patient‐specific intensive PR program.

Level of Evidence

IV
A new model for evaluating maintenance energy requirements in dogs: allometric equation from 319 pet dogs
Authors: Divol Guilhem , Priymenko Nathalie
Published: October 2017

Reports concerning maintenance energy requirements (MER) in dogs are common but most of the data cover laboratory or utility dogs. This study establishes those of healthy adult pet dogs and the factors which cause these energy requirements to vary. Within the framework of a nutrition teaching exercise, each student followed a pet from his entourage and gathered accurate records of its feeding habits. Data have been restricted to healthy adult dogs with an ideal body weight (BW) which did not vary more than 5 % during the study period. A total of 319 eligible records were analysed using multiple linear regression. Variation factors such as ownership, breed, sex and neutered status, bedding location, temperament and feeding habits were then analysed individually using a non-parametric model. Two models result from this study, one excluding age (r2 0·813) and a more accurate one which takes into consideration the age in years (r2 0·816). The second model was assessed with the main variation factors and shows that: MER (kcal) = k1 × k2 × k3 × k4 × k5 × 128 × BW0·740 × age−0·050/d (r2 0·836), with k1 the effect of the breed, k2 the effect of sex and neutered status, k3 the effect of bedding location, k4 the effect of temperament and k5 the effect of the type of feed. The resulting model is very similar to the recommendations made by the National Research Council (2006) but a greater accuracy was obtained using age raised to a negative power, as demonstrated in human nutrition.
PLATO'S PILOT IN THE POLITICAL STRATEGY OF JULIAN AND LIBANIUS
Authors: Greenwood David Neal
Published: October 2017

The rhetorical career of Libanius of Antioch (a.d.314–c.393) spanned the reigns of a number of fourth-century emperors. Like many orators, he used the trope of the emperor as a pilot, steering the ship of state. He did this for his imperial exemplar Julian and in fact for his predecessor Constantius II as well. Julian sought to craft an identity for himself as a theocratic king. He and his supporters cast him as an earthly parallel to the Christ-like versions of Heracles and Asclepius he constructed, which was arguably a co-opting of Christian and particularly Constantinian themes. In a public oration, Julian even placed himself in the role of Christ in the Temptation in the Wilderness. This kind of overtly Christian metaphor was not Libanius’ preferred idiom, however, and he wrote of Julian as another kind of chosen and divine saviour-figure, one with its roots in the golden age of Greek philosophy. The figure of the κυβερνήτης, the ‘pilot’ or ‘helmsman’, is a philosophical concept with roots in the thought of the pre-Socratics but most familiar from Plato. The uses of this metaphor by Julian and Libanius highlight the rhetorical strategy and self-presentation the emperor employed during his reign.
Molecular variance and population structure of lentil (Lens culinarisMedik.) landraces from Mediterranean countries as revealed by simple sequence repeat DNA markers: implications for conservation and use
Authors: Idrissi Omar , Piergiovanni Angela R. , Toklu Faruk , Houasli Chafika , Udupa Sripada M. , De Keyser Ellen , Van Damme Patrick , De Riek Jan
Published: October 2017

The Mediterranean region has a rich history of domestication and cultivation of lentil (Lens culinarisMedik.). Landraces have been grown and repeatedly selected by local farmers under different agro-environments. Characterization of molecular variation and genetic differentiation helps to ensure enhanced valorization, conservation and use of these genetic resources. Nineteen Simple Sequence Repeat DNA markers were used for molecular variance analysis (AMOVA) and population structure assessment underlying 74 lentil landraces from four Mediterranean countries: Morocco, Italy, Greece and Turkey. Based on AMOVA, presence of population structure and genetic differentiation at different levels were evidenced. Genetic diversity among Turkish landraces was higher than that of other countries. These landraces were more homogeneous as shown by low genetic differentiation among individuals within each landrace. Whereas Moroccan landraces followed by Italian and Greek provenances showed higher diversity and differentiation among individuals within landraces. The wide genetic variability of these landraces could help to better adaptation to biotic and abiotic stresses. Moreover, they could provide useful alleles related to adaptive traits for breeding purposes. Based on structure analysis, we obtained indications of possible presence of two major gene pools: a northern gene pool composed of Turkish, Italian and Greek landraces, and a southern gene pool composed of Moroccan landraces. Our results could be of interest when designing future diversity studies, collection missions, conservation and core collection construction strategies on Mediterranean lentil landraces.
Research on a ‘drug-centred’ approach to psychiatric drug treatment: assessing the impact of mental and behavioural alterations produced by psychiatric drugs
Authors: Moncrieff J.
Published: October 2017

Aims.

This article explores an alternative understanding of how psychiatric drugs work that is referred to as the drug-centred model of drug action. Unlike the current disease-centred model, which suggests that psychiatric drugs work by correcting an underlying brain abnormality, the drug-centred model emphasises how psychiatric drugs affect mental states and behaviour by modifying normal brain processes. The alterations produced may impact on the emotional and behavioural problems that constitute the symptoms of mental disorders.

Methods.

Arguments are put forward that justify the consideration of the drug-centred model. The research necessary to support the prescription of drugs according to such a model is explored.

Results.

Evidence from neurochemistry and comparative drug trials do not confirm the disease-centred model of drug action. Since psychiatric drugs are recognised to have mind- and behaviour-altering properties, the drug-centred model constitutes a plausible alternative. The drug-centred model suggests that research is needed to identify all the alterations produced by various sorts of drugs, both acute and long term, and how these might interact with the symptoms and problems associated with different mental disorders. This requires detailed animal and volunteer studies and data from patients prescribed drug treatment long term, along with placebo-controlled and comparative trials that look at the overall impact of drug-induced alterations on well-being and functioning as well as symptoms. Research is also needed on alternative ways of fulfilling the function of drug treatment. The moral aspect of using drugs to modify behaviour rather than treat disease needs honest and transparent consideration.

Conclusions.

It is hoped this discussion will encourage the psychiatric and pharmaceutical research community to provide more of the information that is required to use psychiatric drugs safely and effectively.
Angles of Plasma Ropes near Mars Point to Different Origins
Authors: Stanley Sarah
Published: October 2017

Variation in the orientation of flux rope features in Mars’s magnetotail suggests that some of them form on the planet’s Sun-facing side and travel to the night side.
BCR–ABL1-induced downregulation of WASP in chronic myeloid leukemia involves epigenetic modification and contributes to malignancy
Authors: Pereira Welbert O , De Carvalho Daniel D , Zenteno Maria Emilia , Ribeiro Beatriz F , Jacysyn Jacqueline F , Sardinha Luiz R , Zanichelli Maria A , Hamerschlak Nelson , Jones Gareth E , Pagnano Katia B , Castro Fabiola A , Calle Yolanda , Amarante-Mendes Gustavo P
Published: October 2017

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR–ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR–ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Wiskott–Aldrich syndrome protein (WASP) is an important regulator of signaling transduction in hematopoietic cells and was shown to be an endogenous inhibitor of the c-ABL TK. Here, we show that the expression of WASP decreases with the progression of CML, inversely correlates with the expression of BCR–ABL1 and is particularly low in blast crisis. Enforced expression of BCR–ABL1 negatively regulates the expression of WASP. Decreased expression of WASP is partially due to DNA methylation of the proximal WASP promoter. Importantly, lower levels of WASP in CML advanced phase patients correlate with poorer overall survival (OS) and is associated with TKI response. Interestingly, enforced expression of WASP in BCR–ABL1-positive K562 cells increases the susceptibility to apoptosis induced by TRAIL or chemotherapeutic drugs and negatively modulates BCR–ABL1-induced tumorigenesis in vitro and in vivo. Taken together, our data reveal a novel molecular mechanism that operates in BCR–ABL1-induced tumorigenesis that can be used to develop new strategies to help TKI-resistant, CML patients in blast crisis (BC).
miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by suppressing MYO6
Authors: Lei Chao , Du Feng , Sun Lina , Li Ting , Li Tingyu , Min Yali , Nie Aiying , Wang Xin , Geng Lei , Lu Yuanyuan , Zhao Xiaodi , Shi Yongquan , Fan Daiming
Published: October 2017

Metastasis is a major clinical obstacle responsible for the high mortality and poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators of metastasis that act by modulating their target genes. In this study, we found that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the epithelial–mesenchymal transition (EMT) and inhibit metastasis. We determined that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of miR-143 and/or miR-145 inhibited GC cell migration and metastasis. Furthermore, MYO6 was identified as a direct common target of miR-143 and miR-145 and was elevated in GC. Silencing of MYO6 resulted in a metastasis-suppressive activity similar to that of miR-143 and miR-145, while restoring MYO6 attenuated the anti-metastatic or anti-EMT effects caused by miR-143 and miR-145. Clinically, an inverse correlation was observed between miR-143/145 levels and MYO6 levels in GC tissues, and either miR-143/145 downregulation or MYO6 upregulation was associated with more malignant phenotypes in patients with GC. In conclusion, miR-143 and miR-145 suppress GC cell migration and metastasis by inhibiting MYO6 expression and the EMT, which provides a novel mechanism and promising therapeutic target for the treatment of GC metastasis.
Current progress in the derivation and therapeutic application of neural stem cells
Authors: Tang Yuewen , Yu Pei , Cheng Lin
Published: October 2017

Neural stem cells (NSCs) have a unique role in neural regeneration. Cell therapy based on NSC transplantation is a promising tool for the treatment of nervous system diseases. However, there are still many issues and controversies associated with the derivation and therapeutic application of these cells. In this review, we summarize the different sources of NSCs and their derivation methods, including direct isolation from primary tissues, differentiation from pluripotent stem cells and transdifferentiation from somatic cells. We also review the current progress in NSC implantation for the treatment of various neural defects and injuries in animal models and clinical trials. Finally, we discuss potential optimization strategies for NSC derivation and propose urgent challenges to the clinical translation of NSC-based therapies in the near future.
Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification
Authors: Xu Xiaoliang , Yin Yin , Tang Junwei , Xie Yu , Han Zhuo , Zhang Xudong , Liu Qiaoyu , Qin Xihu , Huang Xinli , Sun Beicheng
Published: October 2017

Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could promote the proliferation and metastasis of HCC both in vitro and in vivo. In addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the activation of both NF-κB and PI3K/AKT signal pathways. In conclusion, we proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target for HCC.
c-Abl-mediated Drp1 phosphorylation promotes oxidative stress-induced mitochondrial fragmentation and neuronal cell death
Authors: Zhou Lujun , Zhang Qiang , Zhang Peng , Sun Lei , Peng Can , Yuan Zengqiang , Cheng Jinbo
Published: October 2017

Oxidative stress-induced mitochondrial dysfunction and neuronal cell death have important roles in the development of neurodegenerative diseases. Dynamin related protein 1 (Drp1) is a critical factor in regulating mitochondrial dynamics. A variety of posttranslational modifications of Drp1 have been reported, including phosphorylation, ubiquitination, sumoylation and S-nitrosylation. In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation. Consistently, c-Abl-mediated phosphorylation is important for GTPase activity of Drp1 and mitochondrial fragmentation. Furthermore, we found that Drp1 phosphorylation mediated by c-Abl is required for oxidative stress-induced cell death in primary cortical neurons. Taken together, our findings reveal that c-Abl-Drp1 signaling pathway regulates oxidative stress-induced mitochondrial fragmentation and cell death, which might be a potential target for the treatment of neurodegenerative diseases.
Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production
Authors: Zhang Min , Wang Jiancheng , Deng Chunhua , Jiang Mei Hua , Feng Xin , Xia Kai , Li Weiqiang , Lai Xingqiang , Xiao Haipeng , Ge Ren-shan , Gao Yong , Xiang Andy Peng
Published: October 2017

Previous studies have demonstrated that rodent stem Leydig cell (SLC) transplantation can partially restore testosterone production in Leydig cell (LC)-disrupted or senescent animal models, which provides a promising approach for the treatment of hypogonadism. Here, we isolated human SLCs prospectively and explored the potential therapeutic benefits of human SLC transplantation for hypogonadism treatment. In adult human testes, p75 neurotrophin receptor positive (p75+) cells expressed the known SLC marker nestin, but not the LC lineage marker hydroxysteroid dehydrogenase-3β (HSD3β). The p75+ cells which were sorted by flow cytometry from human adult testes could expand in vitro and exhibited clonogenic self-renewal capacity. The p75+ cells had multi-lineage differentiation potential into multiple mesodermal cell lineages and testosterone-producing LCs in vitro. After transplantation into the testes of ethane dimethane sulfonate (EDS)-treated LC-disrupted rat models, the p75+ cells differentiated into LCs in vivo and secreted testosterone in a physiological pattern. Moreover, p75+ cell transplantation accelerated the recovery of serum testosterone levels, spermatogenesis and reproductive organ weights. Taken together, we reported a method for the identification and isolation of human SLCs on the basis of p75 expression, and demonstrated that transplanted human p75+ SLCs could replace disrupted LCs for testosterone production. These findings provide the groundwork for further clinical application of human SLCs for hypogonadism.
A mechanosensitive Ca2+ channel activity is dependent on the developmental regulator DEK1
Authors: Tran Daniel , Galletti Roberta , Neumann Enrique D. , Dubois Annick , Sharif-Naeini Reza , Geitmann Anja , Frachisse Jean-Marie , Hamant Olivier , Ingram Gwyneth C.
Published: October 2017

Responses of cells to mechanical stress are thought to be critical in coordinating growth and development. Consistent with this idea, mechanically activated channels play important roles in animal development. For example, the PIEZO1 channel controls cell division and epithelial-layer integrity and is necessary for vascular development in mammals. In plants, the actual contribution of mechanoperception to development remains questionable because very few putative mechanosensors have been identified and the phenotypes of the corresponding mutants are rather mild. Here, we show that the Arabidopsis Defective Kernel 1 (DEK1) protein, which is essential for development beyond early embryogenesis, is associated with a mechanically activated Ca2+ current in planta, suggesting that perception of mechanical stress plays a critical role in plant development.
ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs
Authors: Mrass Paulus , Oruganti Sreenivasa Rao , Fricke G. Matthew , Tafoya Justyna , Byrum Janie R. , Yang Lihua , Hamilton Samantha L. , Miller Mark J. , Moses Melanie E. , Cannon Judy L.
Published: October 2017

Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue. Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature. Rho-associated protein kinase (ROCK) is required for both high-speed migration and straight motion. By contrast, inhibition of Gαisignaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells. Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells. These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.
Few-femtosecond passage of conical intersections in the benzene cation
Authors: Galbraith M. C. E. , Scheit S. , Golubev N. V. , Reitsma G. , Zhavoronkov N. , Despré V. , Lépine F. , Kuleff A. I. , Vrakking M. J. J. , Kornilov O. , Köppel H. , Mikosch J.
Published: October 2017

Observing the crucial first few femtoseconds of photochemical reactions requires tools typically not available in the femtochemistry toolkit. Such dynamics are now within reach with the instruments provided by attosecond science. Here, we apply experimental and theoretical methods to assess the ultrafast nonadiabatic vibronic processes in a prototypical complex system—the excited benzene cation. We use few-femtosecond duration extreme ultraviolet and visible/near-infrared laser pulses to prepare and probe excited cationic states and observe two relaxation timescales of 11 ± 3 fs and 110 ± 20 fs. These are interpreted in terms of population transfer via two sequential conical intersections. The experimental results are quantitatively compared with state-of-the-art multi-configuration time-dependent Hartree calculations showing convincing agreement in the timescales. By characterising one of the fastest internal conversion processes studied to date, we enter an extreme regime of ultrafast molecular dynamics, paving the way to tracking and controlling purely electronic dynamics in complex molecules.
The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells
Authors: Huggins Ian J. , Bos Tomas , Gaylord Olivia , Jessen Christina , Lonquich Brianna , Puranen Angeline , Richter Jenna , Rossdam Charlotte , Brafman David , Gaasterland Terry , Willert Karl
Published: October 2017

The WNT/β-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior–posterior axis specification, organ and tissue development, and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wild-type and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT signaling is most robust in cells with developmental potential, such as stem cells. These findings indicate a mechanism by which the developmental WNT signaling pathway reins in expression of transcriptional programs.
Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer
Authors: Farahani Hossein , de Souza Camila P. E. , Billings Raewyn , Yap Damian , Shumansky Karey , Wan Adrian , Lai Daniel , Mes-Masson Anne-Marie , Aparicio Samuel , P. Shah Sohrab
Published: October 2017

Characterization and quantification of tumour clonal populations over time via longitudinal sampling are essential components in understanding and predicting the response to therapeutic interventions. Computational methods for inferring tumour clonal composition from deep-targeted sequencing data are ubiquitous, however due to the lack of a ground truth biological data, evaluating their performance is difficult. In this work, we generate a benchmark data set that simulates tumour longitudinal growth and heterogeneity by in vitro mixing of cancer cell lines with known proportions. We apply four different algorithms to our ground truth data set and assess their performance in inferring clonal composition using different metrics. We also analyse the performance of these algorithms on breast tumour xenograft samples. We conclude that methods that can simultaneously analyse multiple samples while accounting for copy number alterations as a factor in allelic measurements exhibit the most accurate predictions. These results will inform future functional genomics oriented studies of model systems where time series measurements in the context of therapeutic interventions are becoming increasingly common. These studies will need computational models which accurately reflect the multi-factorial nature of allele measurement in cancer including, as we show here, segmental aneuploidies.
Molecular structure of starch isolated from jackfruit and its relationship with physicochemical properties
Authors: Zhang Yanjun , Zhang Yutong , Xu Fei , Wu Gang , Tan Lehe
Published: October 2017

The molecular structure of starches isolated from five jackfruits (M2, M3, M4, M8 and X1) and its relationship with physicochemical properties were investigated. Although they had uniform amylose (AM) content, the five jackfruit starches displayed different physicochemical properties, including their pasting, thermal, crystal and texture properties. Furthermore, differences in the molecular structure (i.e., average weight-average molar mass (Mw) of amylose and amylopectin (AP) as well as the same AP fine structure) were also found in the five jackfruit starches. The results indicated that jackfruit starch with a larger Mw of amylose and proportions of DP 25–36, DP ≥ 37 and chain length had a lower peak viscosity, breakdown, final viscosity, setback and adhesiveness, but a higher pasting and gelatinization temperature, gelatinization temperature range, gelatinization enthalpy and relative crystallinity. Xiangyinsuo 1 hao (X1) starch, which originated from Xinglong in Hainan province, China, had special physicochemical properties, which were ascribed to its lower amylopectin Mw, smaller particle size, and perfect amylopectin structure. The results showed that the most important intrinsic factors that could determine the physicochemical properties of starch were its molecular structure, including the Mw of amylose and AP as well as a fine AP structure.
The piecewise parabolic method for Riemann problems in nonlinear elasticity
Authors: Zhang Wei , Wang Tao , Bai Jing-Song , Li Ping , Wan Zhen-Hua , Sun De-Jun
Published: October 2017

We present the application of Harten-Lax-van Leer (HLL)-type solvers on Riemann problems in nonlinear elasticity which undergoes high-load conditions. In particular, the HLLD (“D” denotes Discontinuities) Riemann solver is proved to have better robustness and efficiency for resolving complex nonlinear wave structures compared with the HLL and HLLC (“C” denotes Contact) solvers, especially in the shock-tube problem including more than five waves. Also, Godunov finite volume scheme is extended to higher order of accuracy by means of piecewise parabolic method (PPM), which could be used with HLL-type solvers and employed to construct the fluxes. Moreover, in the case of multi material components, level set algorithm is applied to track the interface between different materials, while the interaction of interfaces is realized through HLLD Riemann solver combined with modified ghost method. As seen from the results of both the solid/solid “stick” problem with the same material at the two sides of contact interface and the solid/solid “slip” problem with different materials at the two sides, this scheme composed of HLLD solver, PPM and level set algorithm can capture the material interface effectively and suppress spurious oscillations therein significantly.
Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures
Authors: Schwalbe E. C. , Hicks D. , Rafiee G. , Bashton M. , Gohlke H. , Enshaei A. , Potluri S. , Matthiesen J. , Mather M. , Taleongpong P. , Chaston R. , Silmon A. , Curtis A. , Lindsey J. C. , Crosier S. , Smith A. J. , Goschzik T. , Doz F. , Rutkowski S. , Lannering B. , Pietsch T. , Bailey S. , Williamson D. , Clifford S. C.
Published: October 2017

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.
Facilitating identification of minimal protein binding domains by cross-linking mass spectrometry
Authors: Liu Qingyang , Remmelzwaal Sanne , Heck Albert J. R. , Akhmanova Anna , Liu Fan
Published: October 2017

Characterization of protein interaction domains is crucial for understanding protein functions. Here we combine cross-linking mass spectrometry (XL-MS) with deletion analysis to accurately locate minimal protein interaction domains. As a proof of concept, we investigated in detail the binding interfaces of two protein assemblies: the complex formed by MICAL3, ELKS and Rab8A, which is involved in exocytosis, and the complex of SLAIN2, CLASP2 and ch-TOG, which controls microtubule dynamics. We found that XL-MS provides valuable information to efficiently guide the design of protein fragments that are essential for protein interaction. However, we also observed a number of cross-links between polypeptide regions that were dispensable for complex formation, especially among intrinsically disordered sequences. Collectively, our results indicate that XL-MS, which renders distance restrains of linked residue pairs, accelerates the characterization of protein binding regions in combination with other biochemical approaches.
Association between Parkinson’s disease and risk of prostate cancer in different populations: An updated meta-analysis
Authors: Chen Chunli , Zheng Haiping , Hu Zhiping
Published: October 2017

Recently, growing evidence has revealed a significant association between Parkinson’s disease (PD) and cancer. However, controversy still exists concerning the association between PD and prostate cancer. A comprehensive article search for relevant published studies was performed using the online databases PubMed, Web of Science and Embase up to January 1, 2017. The pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using the method of inverse variance with a random-effects model. Fifteen studies comprising 346,153 PD patients were included in this study. The results of the present study showed that PD was significantly associated with a decreased risk of prostate cancer in the Western population (RR: 0.83, 95% CI: 0.72–0.95, P < 0.01), while an increased risk of prostate cancer was shown in the Asian population (RR: 1.80, 95% CI: 1.52–2.13, P < 0.001). In the subgroup analysis, the reduced risk of prostate cancer in PD patients from Western populations was consistent regardless of study design or study quality. In conclusion, PD was significantly associated with a reduced risk of prostate cancer in the Western population. The relationship between those conditions in the Asian population needs to be confirmed by future studies.
Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification
Authors: Kurosaki Yohei , Martins Danyelly Bruneska Gondim , Kimura Mayuko , Catena Andriu dos Santos , Borba Maria Amélia Carlos Souto Maior , Mattos Sandra da Silva , Abe Haruka , Yoshikawa Rokusuke , de Lima Filho José Luiz , Yasuda Jiro
Published: October 2017

The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID50/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks.
Circulating miR-19b and miR-181b are potential biomarkers for diabetic cardiomyopathy
Authors: Copier Camila Uribe , León Luis , Fernández Mauricio , Contador David , Calligaris Sebastián D.
Published: October 2017

Diabetic cardiomyopathy is characterized by metabolic changes in the myocardium that promote a slow and silent dysfunction of muscle fibers, leading to myocardium remodelling and heart failure, independently of the presence of coronary artery diseases or hypertension. At present, no imaging methods allow an early diagnosis of this disease. Circulating miRNAs in plasma have been proposed as biomarkers in the prognosis of several cardiac diseases. This study aimed to determine whether circulating miRNAs could be potential biomarkers of diabetic cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and a progressive cardiac function decline. At 16 months, when maximal degree of cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in myocardium were selected. Then, selected miRNAs expression in myocardium (at 4 and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR. Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium levels during the development of diabetic cardiomyopathy (in terms of cardiac dysfunction), suggesting that these miRNAs could be suitable biomarkers of this disease in asymptomatic diabetic patients.
Rapid Generation and Detection of Biomimetic Oxygen Concentration Gradients In Vitro
Authors: Khan Daud H. , Roberts Steven A. , Cressman John Robert , Agrawal Nitin
Published: October 2017

Hypoxic regions exist within most solid tumors and often lead to altered cellular metabolism, metastasis, and drug resistance. Reliable generation and detection of biomimetic gaseous gradientsin vitrois challenging due to low spatiotemporal resolution and poor longevity of gradients utilizing microfluidic techniques. Here, we present a novel and simplistic approach for producing gradients of dissolved oxygen (DO) within a lab-on-a-chip platform. Linear and stable DO gradients with high spatial resolution are established by introducing pre-gassed media into the gradient generating network. An underlying platinum(ii) octaethlporphyrin ketone (PtOEPK) based sensor layer allows parallel detection of oxygen. A thin 3-sided glass coating on the inner channel walls prevents multi-directional diffusion of ambient oxygen across PDMS preserving the gradient resolution and stability. Viability analysis of normal mammary epithelial cells (MCF-12A) under oxygen gradients revealed 70% mortality after 6 hours of hypoxic exposure. Biological applicability of the platform was further validated by demonstrating increase in endoplasmic reticulum stress of MDA-MB-468 cells with time and with increasing oxygen tension. The unique ability to establish parallel or opposing gradients of gases and chemicals offers the potential for a wide range of applications in therapeutic development, and fundamental understanding of cellular behavior during hypoxia.
TGF-β signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells
Authors: Shinohara Naohiro , Maeda Shingo , Yahiro Yuhei , Sakuma Daisuke , Matsuyama Kanehiro , Imamura Katsuyuki , Kawamura Ichiro , Setoguchi Takao , Ishidou Yasuhiro , Nagano Satoshi , Komiya Setsuro
Published: October 2017

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells compared with C28/I2 normal chondrocytes, while TGF-β1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-β signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-β and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-β signalling are mutually inhibitory in chondrosarcoma cells.
Growth factors regulate phospholipid biosynthesis in human fibroblast-like synoviocytes obtained from osteoarthritic knees
Authors: Sluzalska Katarzyna D. , Liebisch Gerhard , Wilhelm Jochen , Ishaque Bernd , Hackstein Holger , Schmitz Gerd , Rickert Markus , Steinmeyer Juergen
Published: October 2017

Elevated levels of growth factors and phospholipids (PLs) have been found in osteoarthritic synovial fluid (SF), although the metabolic regulation of PLs is currently unknown. This study aimed to determine the effects of growth factors on the biosynthesis of PLs by fibroblast-like synoviocytes (FLS) obtained from human osteoarthritic knee joints. Electrospray ionization tandem mass spectrometry was applied to analyse the newly synthesized PLs. In the presence of stable isotope-labelled PL precursors, cultured FLS were treated with either transforming growth factor-β1 (TGF-β1), bone morphogenetic protein (BMP)-2, BMP-4, BMP-7 or insulin-like growth factor-1 (IGF-1) alone or in combination with specific inhibitors of cell signalling pathways. TGF-β1 and IGF-1 markedly stimulated the biosynthesis of phosphatidylcholine (PC) before sphingomyelin (SM) and lysophosphatidylcholine (LPC) species were stimulated. BMPs elaborated less pronounced effects. The BMPs tested have different potentials to induce the biosynthesis of phosphatidylethanolamine (PE) and PE-based plasmalogens. Our study shows for the first time that TGF-β1 and IGF-1 substantially regulate the biosynthesis of PC, SM and LPC in human FLS. The functional consequences of elevated levels of PLs require additional study. The BMPs tested may be joint protective in that they upregulate PE-based plasmalogens that function as endogenous antioxidants against reactive oxygen species.
New magnetostratigraphic evidence for the age of Acheulean tools at the archaeo-palaeontological site “Solana del Zamborino” (Guadix – Baza Basin, S Spain)
Authors: Álvarez-Posada C. , Parés J. M. , Sala R. , Viseras C. , Pla-Pueyo S.
Published: October 2017

The sedimentary record in the Guadix-Baza Basin (southern Spain) has proved to be a great source of information for the Miocene through the Pleistocene periods, due to the abundant faunal remains preserved, in some cases associated with lithic tools. The Solana del Zamborino (SZ) section has been the subject of controversy ever since a magnetostratigraphic analysis resulted in an age of 750–770 Kyr for Acheulean tools, a chronology significantly older than the ~600 Kyr established chronology for the first Acheulean record in Europe. Although recent findings at the “Barranc de la Boella” site (north-east of the Iberian Peninsula) seem to indicate that an earlier introduction of such technique in Europe around 0.96–0.781 Ma is possible, the precise age of the classical site at SZ is still controversial. The aim of this paper is to constrain the chronology of the site by developing a longer magnetostratigraphic record. For this purpose, we carried out an exhaustive sampling in a new succession at SZ. Our results provide a ~65 m magnetostratigraphic record in which 4 magnetozones of normal polarity are found. Our new magnetostratigraphic data suggest an age range between 300–480 Kyr for the lithic tools, closer to the age of traditional Acheulean sites in Europe.
Zebrafish aversive taste co-receptor is expressed in both chemo- and mechanosensory cells and plays a role in lateral line development
Authors: Mojib Nazia , Xu Jin , Bartolek Zinka , Imhoff Barry , McCarty Nael A. , Shin Chong Hyun , Kubanek Julia
Published: October 2017

Fishes rely on both chemical and tactile senses to orient themselves to avoid predators, and to detect and taste food. This is likely achieved by highly coordinated reception of signals by mechano- and chemosensory receptors in fish. A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), was previously found to be involved in recognition of triterpene glycosides, a family of naturally occurring compounds that act as chemical defenses in various prey species. However, its localization, function, and how it impacts sensory organ development in vivo is not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical microvilli of the chemosensory cells of taste buds including the epithelium of lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts belonging to the lateral line system. Loss-of-function analyses of RL-TGR resulted in significantly decreased number of neuromasts in the posterior lateral line system and decreased body length, suggesting that RL-TGR is involved in deposition and migration of the neuromasts. Collectively, these results provide the first in vivo genetic evidence of sensory cell-specific expression of this unusual co-receptor and reveal its additional role in the lateral line development in zebrafish.
An endophytic microbe from an unusual volcanic swamp corn seeks and inhabits root hair cells to extract rock phosphate
Authors: Shehata Hanan R. , Dumigan Christopher , Watts Sophia , Raizada Manish N.
Published: October 2017

In the animal microbiome, localization of microbes to specific cell types is well established, but there are few such examples within the plant microbiome which includes endophytes. Endophytes are non-pathogenic microbes that inhabit plants. Root hairs are single cells, equivalent to the nutrient-absorbing intestinal microvilli of animals, used by plants to increase the root surface area for nutrient extraction from soil including phosphorus (P). There has been significant interest in the microbiome of intestinal microvilli but less is known about the root hair microbiome. Here we describe a bacterial endophyte (3F11) from Zea nicaraguensis, a wild corn discovered in a Nicaraguan swamp above rock-P lava flowing from the San Cristobal volcano. Rock-P is insoluble and a major challenge for plants. Following seed coating and germination on insoluble-P, the endophyte colonized epidermal surfaces, ultimately colonizing root hairs intracellularly. The endophyte promoted root hair growth and secreted acids to solubilize rock-P for uptake by a larger root hair surface. The most interesting observation was that a seed-coated endophyte targeted and colonized a critical cell type, root hair cells, consistent with earlier studies. The endophyte maintained its targeting ability in two evolutionary divergent hosts, suggesting that the host recognition machinery is conserved.
Principles of mucin structure: implications for the rational design of cancer vaccines derived from MUC1-glycopeptides
Authors: Martínez-Sáez Nuria , Peregrina Jesús M. , Corzana Francisco
Published: October 2017

Conformational features of tumour-associated MUC1 in both solution and bound states and their implications for the design of cancer vaccines.
Highly sensitive surface-enhanced Raman scattering detection of adenosine triphosphate based on core–satellite assemblies
Authors: Tian Ya-Fei , Zhou Wen , Yin Bin-Cheng , Ye Bang-Ce
Published: October 2017

As an important small molecule, adenosine triphosphate (ATP) plays an important role in the regulation of cell metabolism and supplies energy for various biochemical reactions in organisms.