bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetric comparison between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in the treatment of different stages of nasopharyngeal carcinoma
Authors: Ibrahim Mohamed S. , Attalla Ehab M. , El Naggar Mostafa , Elshemey Wael M.
Published: September 2018

Background

This work aims to compare the dosimetric performance of three-dimensional conformal radiotherapy (3D-CRT), a relatively available technique in developing countries, to intensity-modulated radiotherapy (IMRT) in the treatment of different stages of nasopharyngeal carcinoma (NPC).

Materials and Methods

According to the diagnostic stages, 40 NPC patients were divided into two equal groups. Three planning techniques such as 3D-CRT, seven-field IMRT (7F-IMRT) and nine-field IMRT (9F-IMRT) were compared. Dose prescriptions of 70 and 66 Gy were delivered in 35 fractions to gross planning target volume (PTV1) and bilateral retropharyngeal carcinoma (PTV2), respectively.

Results

Stage I dose data for almost all of the three investigated planning techniques obey the international recommendations. The dose delivered to PTV1 and PTV2 for 3D-CRT and 7F-IMRT are statistically similar, whereas 9F-IMRT is significantly better than 3D-CRT. For organs at risk (OARs), the delivered dose is significantly better for 9F-IMRT compared with the other two techniques, whereas 7F-IMRT is significantly better than 3D-CRT.

Conclusions

3D-CRT is an acceptable alternative treatment technique for stage I NPC patients in developing countries suffering from the lack of advanced radiotherapy treatment techniques. 3D-CRT and 7F-IMRT have comparable performance in PTVs, while 9F-IMRT is superior in PTVs and OARs.
Virtual reality as a distraction technique for pain and anxiety among patients with breast cancer: A randomized control trial
Authors: Bani Mohammad Eslam , Ahmad Muayyad
Published: September 2018

Objective

The goal of this study was to assess the effectiveness of immersive virtual reality (VR) distraction technology in reducing pain and anxiety among female patients with breast cancer.

Method

A randomized control trial design was used with a sample of 80 female patients with breast cancer at a specialized cancer center in Jordan. Participants were randomly assigned into intervention and comparison groups.

Result

The study findings showed that one session of the immersive VR plus morphine made a significant reduction in pain and anxiety self-reported scores, compared with morphine alone, in breast cancer patients.

Significance of results

Immersive VR is an effective distraction intervention for managing pain and anxiety among breast cancer patients. Using immersive VR as an adjuvant intervention is more effective than morphine alone in relieving pain and anxiety; furthermore, VR is a safe intervention more than pharmacological treatment.
Effects of Size and Temperature‐Dependent Thermal Conductivity on the Cooling of Pyroclasts in Air
Authors: Moitra Pranabendu , Sonder Ingo , Valentine Greg A.
Published: September 2018

The knowledge of the cooling time scales of pyroclasts, in conditions of free to forced convection, is of paramount importance in microtextural analysis, development of welded deposits, and in eruption column and pyroclast flow modeling. We performed cooling experiments of heated rock inside a cylindrical wind tunnel under a range of air speeds. In order to estimate the heat transfer coefficients, we modeled the transient temperature distribution in the sample with temperature‐dependent thermal diffusivity and heat capacity, which were obtained from laser flash measurements. For air speeds up to 15 m/s and for sample temperatures up to 1383 K (1110 ° C), a Nusselt‐Reynolds (Nu‐Re) relationship up to Re=3× 104 is established in this study. We find that the dependency of heat loss on size is particularly important for pyroclasts larger than ∼1 mm. Our results suggest that the cooling time scales of pyroclasts could be large enough to cause postfragmentation modification of clast microtextures. We further show that clasts of few‐centimeter and larger develop solid crusts with molten cores within time scales of a few minutes and therefore may inhibit postdepositional welding.
The 2018 MW 7.9 Gulf of Alaska Earthquake: Multiple Fault Rupture in the Pacific Plate
Authors: Lay Thorne , Ye Lingling , Bai Yefei , Cheung Kwok Fai , Kanamori Hiroo
Published: September 2018

A major (MW 7.9) intraplate earthquake ruptured the Pacific plate seaward of the Alaska subduction zone near Kodiak Island on 23 January 2018. The aftershock seismicity is diffuse, with both NNW‐ and ENE‐trending distributions, while long‐period point source moment tensors have near‐horizontal compressional and tensional principal strain axes and significant non‐double‐couple components. Backprojections from three large‐aperture networks indicate sources of short‐period radiation not aligned with the best double‐couple fault planes. A suite of finite‐fault rupture models with one to four faults was considered, and a four‐fault model, dominated by right‐lateral slip on an SSE trending, westward‐dipping fault, is compatible with most seismic, GPS, and tsunami data. However, the precise geometry, timing, and slip distribution of the complex set of faults is not well resolved. The sequence appears to be the result of intraplate stresses influenced by slab pull, the 1964 Alaska earthquake, and collision of the Yakutat terrane in northeastern Alaska.
Using the Airborne Snow Observatory to Assess Remotely Sensed Snowfall Products in the California Sierra Nevada
Authors: Behrangi Ali , Bormann Kat J. , Painter Thomas H.
Published: September 2018

The Airborne Snow Observatory (ASO) performed two acquisitions over two mountainous basins in California on 29 January and 3 March 2017, encompassing two atmospheric river events that brought heavy snowfall to the area. These surveys produced high‐resolution (50 m) maps of snow depth and snow water equivalent (SWE) that were used to estimate monthly areal snowfall accumulation. Comparison of ASO snow accumulation with point measurements showed that the ASO estimates ranged from −10 to +16% relative bias across three sites, which is likely inflated by the disagreement in areal representation of the quantities from the actual errors in these products. The aggregated SWE accumulations from ASO are then used to evaluate a suite of in situ based and remote sensing precipitation products. During the study period, Parameter‐Elevation Regressions on Independent Slopes Model (PRISM) and Mountain Mapper estimates had relative bias <10% compared with ASO‐based estimates of snow accumulation, but satellite and radar products largely underestimate snowfall accumulation compared to ASO (up to 50%). Despite their underestimation, satellite and radar products show correlation coefficients >0.8 with ASO snow accumulation over the selected grids at the monthly scale. Finally, we leveraged the fine‐scale sampling of the spatially complete ASO products to show that by moving from 100 m to 2 km spatial scales, the perceived bias errors SWE at point locations increased by an order of magnitude, displaying a nonlinear relationship. The study demonstrates that ASO acquisitions in cold months can bring a new and effective approach to spatial evaluation of precipitation products.
Imaging and Measurement of Pore‐Scale Interfacial Curvature to Determine Capillary Pressure Simultaneously With Relative Permeability
Authors: Lin Qingyang , Bijeljic Branko , Pini Ronny , Blunt Martin J. , Krevor Samuel
Published: September 2018

There are a number of challenges associated with the determination of relative permeability and capillary pressure. It is difficult to measure both parameters simultaneously on the same sample using conventional methods. Instead, separate measurements are made on different samples, usually with different flooding protocols. Hence, it is not certain that the pore structure and displacement processes used to determine relative permeability are the same as those when capillary pressure was measured. Moreover, at present, we do not use pore‐scale information from high‐resolution imaging to inform multiphase flow properties directly. We introduce a method using pore‐scale imaging to determine capillary pressure from local interfacial curvature. This, in combination with pressure drop measurements, allows both relative permeabilities and capillary pressure to be determined during steady state coinjection of two phases through the core. A steady state waterflood experiment was performed in a Bentheimer sandstone, where decalin and brine were simultaneously injected through the core at increasing brine fractional flows from 0 to 1. The local saturation and the curvature of the oil‐brine interface were determined. Using the Young‐Laplace law, the curvature was related to a local capillary pressure. There was a detectable gradient in both saturation and capillary pressure along the flow direction. The relative permeability was determined from the experimentally measured pressure drop and average saturation obtained by imaging. An analytical correction to the brine relative permeability could be made using the capillary pressure gradient. The results for both relative permeability and capillary pressure are consistent with previous literature measurements on larger samples.
Breath acetone as a marker of energy balance: an exploratory study in healthy humans
Authors: Bovey Fabian , Cros Jérémy , Tuzson Béla , Seyssel Kevin , Schneiter Philippe , Emmenegger Lukas , Tappy Luc
Published: September 2018

An exploratory study was performed on eight healthy volunteers to assess how short-term changes in energy balance and dietary carbohydrate content impact breath acetone concentrations. Participants were studied on three occasions: on each occasion, they remained fasted and in resting conditions during the first 2 h to assess basal breath acetone and blood beta-hydroxybutyrate (BOHB). During the next 6 h, they remained fasted on one occasion (F), or were fed hourly high carbohydrate (HC) or low-carbohydrate (LC) meals to induce a positive energy balance on the other two occasions. They remained in resting conditions during 4 h, then performed a 2-hour low intensity exercise (25 W) inducing a negative energy balance. In resting conditions, breath acetone and blood BOHB concentrations increased progressively compared to basal values in F, but decreased and remained low throughout the test in HC. With LC, breath acetone increased progressively, while blood BOHB decreased. This exploratory study indicates that breath acetone reliably detects a stimulation of ketogenesis during a short-term fast. It also suggests that LC and HC differentially impact BOHB and acetone production and utilization, and reveals possible limitations to the use of breath acetone as a marker of energy balance.
HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
Authors: Di Rita Anthea , Peschiaroli Angelo , D′Acunzo Pasquale , Strobbe Daniela , Hu Zehan , Gruber Jens , Nygaard Mads , Lambrughi Matteo , Melino Gerry , Papaleo Elena , Dengjel Jörn , El Alaoui Said , Campanella Michelangelo , Dötsch Volker , Rogov Vladimir V. , Strappazzon Flavie , Cecconi Francesco
Published: September 2018

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells.
Conditional and interaction gene-set analysis reveals novel functional pathways for blood pressure
Authors: de Leeuw Christiaan A. , Stringer Sven , Dekkers Ilona A. , Heskes Tom , Posthuma Danielle
Published: September 2018

Gene-set analysis provides insight into which functional and biological properties of genes are aetiologically relevant for a particular phenotype. But genes have multiple properties, and these properties are often correlated across genes. This can cause confounding in a gene-set analysis, because one property may be statistically associated even if biologically irrelevant to the phenotype, by being correlated with gene properties that are relevant. To address this issue we present a novel conditional and interaction gene-set analysis approach, which attains considerable functional refinement of its conclusions compared to traditional gene-set analysis. We applied our approach to blood pressure phenotypes in the UK Biobank data (N = 360,243), the results of which we report here. We confirm and further refine several associations with multiple processes involved in heart and blood vessel formation but also identify novel interactions, among others with cardiovascular tissues involved in regulatory pathways of blood pressure homoeostasis.
A self-improving triboelectric nanogenerator with improved charge density and increased charge accumulation speed
Authors: Cheng Li , Xu Qi , Zheng Youbin , Jia Xiaofeng , Qin Yong
Published: September 2018

Charge density is one of the most important parameters of triboelectric nanogenerators since it directly determines performance; unfortunately, it is largely restricted by the phenomenon of air breakdown. Here, we design a self-improving triboelectric nanogenerator with improved charge density. A maximum effective charge density of 490 μC m−2 is obtained, which is about two times higher than the highest reported charge density of a triboelectric nanogenerator that operates in an air environment. At the beginning of the working process, the charge accumulation speed is increased 5.8 times in comparison with a triboelectric nanogenerator that is incorporated into the self-improving device. The self-improving triboelectric nanogenerator overcomes the restriction of air breakdown and exhibits an increased effective charge density, which contributes to the improvement of the output performance, and the increase of charge accumulation speed will accelerate the increase of the output power at the start of operation.
Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments
Authors: Yoshitomi Hiroyuki , Kobayashi Shio , Miyagawa-Hayashino Aya , Okahata Akinori , Doi Kohei , Nishitani Kohei , Murata Koichi , Ito Hiromu , Tsuruyama Tatsuaki , Haga Hironori , Matsuda Shuichi , Toguchida Junya
Published: September 2018

In human inflammatory sites, PD-1hiCXCR5−CD4+ T cells are involved in the formation of ectopic lymphoid-like structures (ELSs) by the secretion of chemokine CXCL13, but how the transcription of CXCL13 is regulated in CD4+ T cells is still unclear. Here we show that Sox4 is a key transcription factor for CXCL13 production in human CD4+ T cells under inflammatory conditions. In vitro TGF-β+, IL-2-neutralizing culture conditions give rise to PD-1hiCXCR5−CD4+ T cells that preferentially express CXCL13, and transcriptome analysis and lentiviral overexpression indicate Sox4 association with the CXCL13 transcription. In vivo, Sox4 is significantly upregulated in synovial CD4+ T cells, when compared with blood CD4+ T cells, from patients with rheumatoid arthritis (RA), and further correlates with ELS formation in RA synovium. Overall, our studies suggest that Sox4 contributes to CXCL13 production and ELS formation at inflammatory sites in humans.
Predicting nutrient content of ray-finned fishes using phylogenetic information
Authors: Vaitla Bapu , Collar David , Smith Matthew R. , Myers Samuel S. , Rice Benjamin L. , Golden Christopher D.
Published: September 2018

Human food and nutrition security is dependent on marine ecosystems threatened by overfishing, climate change, and other processes. The consequences on human nutritional status are uncertain, in part because current methods of analyzing fish nutrient content are expensive. Here, we evaluate the possibility of predicting nutrient content of ray-finned fishes using existing phylogenetic and life history information. We focus on nutrients for which fish are important sources: protein, total fat, omega-3 and omega-6 fatty acids, iron, zinc, vitamin A, vitamin B12, and vitamin D. Our results show that life history traits are weak predictors of species nutrient content, but phylogenetic relatedness is associated with similar nutrient profiles. Further, we develop a method for predicting the nutrient content of 7500+ species based on phylogenetic relationships to species with known nutrient content. Our approach is a cost-effective means for estimating potential changes in human nutrient intake associated with altered access to ray-finned fishes.
Nanomaterials design for super-degenerate electronic state beyond the limit of geometrical symmetry
Authors: Haruta Naoki , Tsukamoto Takamasa , Kuzume Akiyoshi , Kambe Tetsuya , Yamamoto Kimihisa
Published: September 2018

Spherical atoms have the highest geometrical symmetry. Due to this symmetry, atomic orbitals are highly degenerate, leading to closed-shell stability and magnetism. No substances with greater degrees of degeneracy are known, due to geometrical limitations. We now propose that realistic magnesium, zinc, and cadmium clusters having a specific tetrahedral framework possess anomalous higher-fold degeneracies than spherical symmetry. Combining density functional theory calculations with simple tight-binding models, we demonstrate that these degeneracies can be attributed to dynamical symmetry. The degeneracy condition is fully identified as an elegant mathematical sequence involving interatomic parameters. The introduction of dynamical symmetry will lead to the discovery of a novel category of substances with super-degenerate orbitals.
The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation
Authors: Mi Wenyi , Zhang Yi , Lyu Jie , Wang Xiaolu , Tong Qiong , Peng Danni , Xue Yongming , Tencer Adam H. , Wen Hong , Li Wei , Kutateladze Tatiana G. , Shi Xiaobing
Published: September 2018

Recognition of histones by epigenetic readers is a fundamental mechanism for the regulation of chromatin and transcription. Most reader modules target specific post-translational modifications on histones. Here, we report the identification of a reader of histone H3, the ZZ-type zinc finger (ZZ) domain of ZZZ3, a subunit of the Ada-two-A-containing (ATAC) histone acetyltransferase complex. The solution NMR structure of the ZZ in complex with the H3 peptide reveals a unique binding mechanism involving caging of the N-terminal Alanine 1 of histone H3 in an acidic cavity of the ZZ domain, indicating a specific recognition of H3 versus other histones. Depletion of ZZZ3 or disruption of the ZZ-H3 interaction dampens ATAC-dependent promoter histone H3K9 acetylation and target gene expression. Overall, our study identifies the ZZ domain of ZZZ3 as a histone H3 reader that is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.
Chromatin swelling drives neutrophil extracellular trap release
Authors: Neubert Elsa , Meyer Daniel , Rocca Francesco , Günay Gökhan , Kwaczala-Tessmann Anja , Grandke Julia , Senger-Sander Susanne , Geisler Claudia , Egner Alexander , Schön Michael P. , Erpenbeck Luise , Kruss Sebastian
Published: September 2018

Neutrophilic granulocytes are able to release their own DNA as neutrophil extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion (NETosis) has also been documented for other cells and organisms, thus highlighting the evolutionary conservation of this process. Moreover, dysregulated NETosis has been implicated in many diseases, including cancer and inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic alterations of their cellular as well as sub-cellular morphology whose biophysical basis is poorly understood. Here we investigate NETosis in real-time on the single-cell level using fluorescence and atomic force microscopy. Our results show that NETosis is highly organized into three distinct phases with a clear point of no return defined by chromatin status. Entropic chromatin swelling is the major physical driving force that causes cell morphology changes and the rupture of both nuclear envelope and plasma membrane. Through its material properties, chromatin thus directly orchestrates this complex biological process.
Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization
Authors: Lee Chih-Chan , Lin Jiunn-Chang , Hwang Wei-Lun , Kuo Ying-Ju , Chen Hung-Kai , Tai Shyh-Kuan , Lin Chun-Chi , Yang Muh-Hwa
Published: September 2018

A favorable interplay between cancer cells and the tumor microenvironment (TME) facilitates the outgrowth of metastatic tumors. Because of the distinct initiating processes between primary and metastatic tumors, we investigate the differences in tumor-associated macrophages (TAMs) from primary and metastatic cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs from primary tumors, whereas predominant expression of M2 markers is shown in metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to facilitate metastatic colonization through activation of JAK2–STAT6-GATA3 signaling to reverse epithelial–mesenchymal transition (EMT) in cancer cells. In primary tumors, inflammation-induced EMT upregulates IL12Rβ2, a subunit of the IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis. Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic colonization. These results indicate the distinct TMEs of primary and metastatic tumors and provide potential targets for intercepting metastasis.
Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations
Authors: Zou Wenyue , González Ana , Jampaiah Deshetti , Ramanathan Rajesh , Taha Mohammad , Walia Sumeet , Sriram Sharath , Bhaskaran Madhu , Dominguez-Vera José M. , Bansal Vipul
Published: September 2018

Spectrally–selective monitoring of ultraviolet radiations (UVR) is of paramount importance across diverse fields, including effective monitoring of excessive solar exposure. Current UV sensors cannot differentiate between UVA, B, and C, each of which has a remarkably different impact on human health. Here we show spectrally selective colorimetric monitoring of UVR by developing a photoelectrochromic ink that consists of a multi-redox polyoxometalate and an e−donor. We combine this ink with simple components such as filter paper and transparency sheets to fabricate low-cost sensors that provide naked-eye monitoring of UVR, even at low doses typically encountered during solar exposure. Importantly, the diverse UV tolerance of different skin colors demands personalized sensors. In this spirit, we demonstrate the customized design of robust real-time solar UV dosimeters to meet the specific need of different skin phototypes. These spectrally–selective UV sensors offer remarkable potential in managing the impact of UVR in our day-to-day life.
The last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts
Authors: Loyer Nicolas , Januschke Jens
Published: September 2018

Controlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division. Using live cell imaging of cultured brains, laser ablation and genetics, we reveal that division axis maintenance relies on their last-born daughter cell. We propose that, in addition to known intrinsic cues, stem cells in the developing fly brain are polarized by an extrinsic signal. We further find that division axis maintenance allows neuroblasts to maximize their contact area with glial cells known to provide protective and proliferative signals to neuroblasts.
Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells
Authors: Chen Xufeng , Zhao Jingyao , Gu Chan , Cui Yu , Dai Yuling , Song Guangrong , Liu Haifeng , Shen Hao , Liu Yuanhua , Wang Yuya , Xing Huayue , Zhu Xiaoyan , Hao Pei , Guo Fan , Liu Xiaolong
Published: September 2018

In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs. Ablation of Med23 in hematopoietic system leads to lymphocytopenia. Med23-deficient HSCs undergo myeloid-biased differentiation and lose the self-renewal capacity. Interestingly, Med23-deficient HSCs are much easier to be activated in response to physiological stresses. Mechanistically, Med23 plays essential roles in maintaining stemness genes expression and suppressing myeloid lineage genes expression. Med23 is downregulated in HSCs and Med23 deletion results in better survival under myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of myeloid potential of HSCs, thus providing unique insights into the relationship among Med23-mediated transcriptional regulations, the myeloid potential of HSCs and HSC activation upon stresses.
Author Correction: Origin of large plasticity and multiscale effects in iron-based metallic glasses
Authors: Sarac Baran , Ivanov Yurii P. , Chuvilin Andrey , Schöberl Thomas , Stoica Mihai , Zhang Zaoli , Eckert Jürgen
Published: September 2018

The authors became aware of a mistake in the original version of this Article. Specifically, where discussing the Curie temperature of the amorphous phase, Tc, in the ‘Thermal characterization’ section of the Results and in Fig. 2, the authors should have been discussing the Curie temperature of the magnetic crystalline phases T’c. While the Curie temperature of the glass is lower than previously reported, this error does not affect the original discussion or conclusions of the Article. The authors apologize for the confusion caused by this mistake. In addition to this, there were errors in some of the equations in the main text, and the glass composition. A number of changes have been made in both the PDF and HTML versions of the Article to reflect these errors. A full list of these changes is available online.
Differences in the intrinsic chondrogenic potential of equine umbilical cord matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration
Authors: Rakic Rodolphe , Bourdon Bastien , Demoor Magali , Maddens Stéphane , Saulnier Nathalie , Galéra Philippe
Published: September 2018

Umbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to standard surgically derived bone marrow or adipose tissue collection for cartilage engineering. However, the majority of comparative studies explore neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in the reproducibility between in vitro and in clinical studies. Therefore, we characterized equine UCB-MSCs and UCM-MSCs and investigated with particular attention their chondrogenesis potential in 3D culture with BMP-2 + TGF-ß1 in normoxia or hypoxia. We carried out an exhaustive characterization of the extracellular matrix generated by both these two types of MSCs after the induction of chondrogenesis through evaluation of hyaline cartilage, hypertrophic and osteogenic markers (mRNA, protein and histology levels). Some differences in hypoxia sensitivity and chondrogenesis were observed. UCB-MSCs differentiated into chondrocytes express an abundant, dense and a hyaline-like cartilage matrix. By contrast, despite their expression of cartilage markers, UCM-MSCs failed to express a relevant cartilage matrix after chondrogenic induction. Both MSCs types also displayed intrinsic differences at their undifferentiated basal status, UCB-MSCs expressing higher levels of chondrogenic markers whereas UCM-MSCs synthesizing higher amounts of osteogenic markers. Our results suggest that UCB-MSCs should be preferred for ex-vivo horse cartilage engineering. How those results should be translated to in vivo direct cartilage regeneration remains to be determined through dedicated study.
A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias associated with dilated cardiomyopathy
Authors: Moreau Adrien , Gosselin-Badaroudine Pascal , Mercier Aurélie , Burger Bettina , Keller Dagmar I. , Chahine Mohamed
Published: September 2018

Dilated cardiomyopathy (DCM) is a structural heart disease that causes dilatation of cardiac chambers and impairs cardiac contractility. The SCN5A gene encodes Nav1.5, the predominant cardiac sodium channel alpha subunit. SCN5A mutations have been identified in patients with arrhythmic disorders associated with DCM. The characterization of Nav1.5 mutations located in the voltage sensor domain (VSD) and associated with DCM revealed divergent biophysical defects that do not fully explain the pathologies observed in these patients. The purpose of this study was to characterize the pathological consequences of a gating pore in the heart arising from the Nav1.5/R219H mutation in a patient with complex cardiac arrhythmias and DCM. We report its properties using cardiomyocytes derived from patient-specific human induced pluripotent stem cells. We showed that this mutation generates a proton leak (called gating pore current). We also described disrupted ionic homeostasis, altered cellular morphology, electrical properties, and contractile function, most probably linked to the proton leak. We thus propose a novel link between SCN5A mutation and the complex pathogenesis of cardiac arrhythmias and DCM. Furthermore, we suggest that leaky channels would constitute a common pathological mechanism underlying several neuronal, neuromuscular, and cardiac pathologies.
High-throughput sequencing revealed that microRNAs were involved in the development of superior and inferior grains in bread wheat
Authors: Wang Yongyan , Shi Chaonan , Yang Tianxiao , Zhao Lei , Chen Jianhui , Zhang Ning , Ren Yan , Tang Guiliang , Cui Dangqun , Chen Feng
Published: September 2018

High-throughput sequencing was employed to investigate the expression of miRNAs and their target genes in superior and inferior seeds of Aikang 58. Small RNA sequencing revealed 620 conserved and 64 novel miRNAs in superior grains, and 623 conserved and 66 novel miRNAs in inferior grains. Among these, 97 known miRNAs, and eight novel miRNAs showed differential expression between the superior and inferior seeds. Degradome sequencing revealed at least 140 candidate target genes associated with 35 miRNA families during the development of superior and inferior seeds. GO and KEGG pathway analysis showed that the differentially expressed miRNAs, both conserved and novel, were likely involved in hormone production, carbohydrate metabolic pathways, and cell division. We validated eight known and four novel grain development-related miRNAs and their target genes by quantitative real-time polymerase chain reaction to ensure the reliability of small RNA and degradome-seq results. Of these, miR160 and miR165/166 were knocked down in Arabidopsis using short-tandem target mimic (STTM160 and STTM165/166) technology, which confirmed their roles in seed development. Specifically, STTM160 showed significantly smaller grain size, lower grain weight, shorter siliques length, shorter plant height, and more serrated leaves, whereas STTM165/166 showed decreased seed number, disabled siliques, and curled upward leaves.
Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging
Authors: Hainfeld James F. , Ridwan Sharif M. , Stanishevskiy Yaroslav , Smilowitz Nathaniel R. , Davis James , Smilowitz Henry M.
Published: September 2018

Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.
Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe
Authors: O’Sullivan D. , Adams M. P. , Tarn M. D. , Harrison A. D. , Vergara-Temprado J. , Porter G. C. E. , Holden M. A. , Sanchez-Marroquin A. , Carotenuto F. , Whale T. F. , McQuaid J. B. , Walshaw R. , Hedges D. H. P. , Burke I. T. , Cui Z. , Murray B. J.
Published: September 2018

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above −18 °C at concentrations >0.1 L−1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.
Within-colony genetic diversity differentially affects foraging, nest maintenance, and aggression in two species of harvester ants
Authors: Saar Maya , Eyer Pierre-André , Kilon-Kallner Tal , Hefetz Abraham , Scharf Inon
Published: September 2018

There is accumulating evidence that genetic diversity improves the behavioral performance and consequently the fitness in groups of social animals. We examined the behavioral performance of colonies of two co-occurring, congeneric harvester ant species (Messor arenarius and a non-described Messor sp.) in fitness-related behaviors, pertaining to foraging performance, nest maintenance, and aggression. We linked these behaviors to the colonial genetic diversity, by genotyping workers, using six and five microsatellite markers for M. arenarius and M. sp., respectively. Correlations of genetic diversity with colony performance and aggression level contrasted between the two species. In M. arenarius, genetic diversity was correlated with foraging performance and nest maintenance but not with the overall aggression level, while in M. sp., genetic diversity was correlated with the overall aggression level, but not with foraging performance or nest maintenance. The two species exhibited similar specific aggression levels, with higher aggression shown towards heterospecifics and lower towards non-nestmate conspecifics and nestmates. However, M. sp. workers displayed a tendency to interact for longer with heterospecifics than did M. arenarius. We speculate that the different foraging strategies, group vs. individual foraging, and possibly also the different mating systems, contribute to the differences found in behavior between the two species.
A new method to improve the prediction of the celestial pole offsets
Authors: Belda Santiago , Ferrándiz José M. , Heinkelmann Robert , Schuh Harald
Published: September 2018

Knowledge of the Earth’s changing rotation is fundamental to positioning objects in space and on the planet. Nowadays, the Earth’s orientation in space is expressed by five Earth Orientation Parameters (EOP). Many applications in astronomy, geosciences, and space missions require accurate EOP predictions. Operational predictions are released daily by the Rapid Service/Prediction Centre of the International Earth Rotation and Reference Systems Service (IERS). The prediction procedures and performances differ for the three EOP classes: polar motion, rotation angle (UT1-UTC), and the two celestial pole offsets (CPO), dX and dY. The IERS Annual Report 2016 shows Rapid Service CPO predictions errors with respect to IERS 08 C04 observations in 2016 ranging from 120 to 140 μas in 40 days for dX, and 100–160 μas for dY. We test a new method for the CPO prediction based on the recent availability of sophisticated empirical models for the Free Core Nutation, a main component of the CPO variations. We found it allows predicting both CPO with error estimates for the period 2000–2016 lower than the 2016 Rapid Service products, reaching about 85 μas after 40 days and near 90 μas after a year. These results would represent a 35–40% improvement.
Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes
Authors: Haukka Jani K. , Sandholm Niina , Forsblom Carol , Cobb Jeffrey E. , Groop Per-Henrik , Ferrannini Ele
Published: September 2018

Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched non-progressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA1c), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.
Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery
Authors: Falanga Annarita , Iachetta Giuseppina , Lombardi Lucia , Perillo Emiliana , Lombardi Assunta , Morelli Giancarlo , Valiante Salvatore , Galdiero Stefania
Published: September 2018

We have investigated the crossing of the blood brain barrier (BBB) by the peptide gH625 and compared to the uptake by liver in vivo. We clearly observed that in vivo administration of gH625 allows the crossing of the BBB, although part of the peptide is sequestered by the liver. Furthermore, we used a combination of biophysical techniques to gain insight into the mechanism of interaction with model membranes mimicking the BBB and the liver. We observed a stronger interaction for membranes mimicking the BBB where gH625 clearly undergoes a change in secondary structure, indicating the key role of the structural change in the uptake mechanism. We report model studies on liposomes which can be exploited for the optimization of delivery tools.
A Small Molecule BH3-mimetic Suppresses Cigarette Smoke-Induced Mucous Expression in Airway Epithelial Cells
Authors: Hussain Shah S. , George Shebin , Singh Shashi , Jayant Rahul , Hu Chien-An , Sopori Mohan , Chand Hitendra S.
Published: September 2018

Cigarette smoke (CS) exposure is one of the primary risk factors associated with the chronic mucous hypersecretion (CMH). The antiapoptotic protein, Bcl-2 sustains hyperplastic mucous cells, and the airway epithelium of ex-smokers with CMH as well as mice exposed to chronic CS showed increased Bcl-2 expression. Therefore, we investigated whether Bcl-2 plays a role in CS-induced mucous expression. Primary airway epithelial cells (AECs) of murine and human origin were treated with CS extract (CSE), and there was a concentration- and time-dependent increase in secretory mucin (MUC5AC), mucous regulator (SPDEF) and Bcl-2 expression. Using differentiated human AECs cultured on air-liquid interface, EGFR and ERK1/2 pathways were interrogated. Bcl-2 activity was blocked using a small molecule BH3 mimetic ABT-263 that disrupts the Bcl-2 interaction with pro-apoptotic proteins. The ABT-263 treatment resulted in the downregulation of CSE-induced mucus expression and disrupted the EGFR-signaling while inducing the apoptosis and the pro-apoptotic protein, Bik expression. This strategy significantly suppressed the mainstream CS-induced mucous phenotype in a 3-D human airway epithelium model. Therefore, the present study suggests that CS induces Bcl-2 expression to help promote mucous cell survival; and small molecule BH3 mimetics targeting Bcl-2 could be useful in suppressing the CS-induced mucous response.
Elevated basal luteinizing hormone does not impair the outcome of human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles
Authors: Sun Lihua , Ye Jing , Wang Yun , Chen Qiuju , Cai Renfei , Fu Yonglun , Tian Hui , Lyu Qifeng , Lu Xuefeng , Kuang Yanping
Published: September 2018

The potential effects of high basal luteinizing hormone (LH) levels on human reproduction were controversial. To demonstrate the effects of elevated basal LH levels on the outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles, we performed a retrospective data analysis of 1011 polycystic ovarian syndrome (PCOS) patients treated with human menopausal gonadotropin and medroxyprogesterone acetate (hMG + MPA) protocol at our center between Nov. 2013 and Jun. 2017. PCOS patients with elevated basal LH levels had significantly higher LH exposure during the stimulation period. The group with LH ≥ 10 mIU/mL showed a lower mean total hMG dose used but higher numbers of oocytes retrieved, metaphase II oocytes, embryos and top-quality embryos developed than the groups with lower basal LH levels. Moreover, partial correlation analysis showed that the basal LH level was negatively correlated with the total hMG dose but positively correlated with the numbers of oocytes retrieved, metaphase II oocytes, embryos, and top-quality embryos. There were no significant differences in the rates of oocyte retrieval, fertilization, implantation, clinical pregnancy and miscarriage between the groups based on frozen embryo transfer (FET). We concluded that elevated basal LH level does not impair the final outcome of hMG + MPA-treated IVF/ICSI cycles in PCOS women.
Early identification of esophageal squamous neoplasm by hyperspectral endoscopic imaging
Authors: Wu I-Chen , Syu Hao-Yi , Jen Chun-Ping , Lu Ming-Yen , Chen Yi-Ting , Wu Ming-Tsang , Kuo Chie-Tong , Tsai Yu-Yuan , Wang Hsiang-Chen
Published: September 2018

Esophageal squamous neoplasm presents a spectrum of different diatheses. A precise assessment for individualized treatment depends on the accuracy of the initial diagnosis. Detection relies on comprehensive and accurate white-light, iodine staining, and narrow-band imaging endoscopy. These methods have limitations in addition to its invasive nature and the potential risks related to the method. These limitations include difficulties in precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and stage determination. The resolution of these problems depends on the surgeon’s ability and experience with available technology for visualization and resection. We proposed a method for identifying early esophageal cancerous lesion by endoscopy and hyperspectral endoscopic imaging. Experimental result shows the characteristic spectrum of a normal esophagus, precancerous lesion, canceration, and intraepithelial papillary capillary loop can be identified through principal component score chart. The narrow-band imaging (NBI) image shows remarkable spectral characteristic distribution, and the sensitivity and specificity of the proposed method are higher than those of other methods by ~0.8 and ~0.88, respectively. The proposed method enables the accurate visualization of target organs, it may be useful to capsule endoscope and telemedicine, which requires highly precise images for diagnosis.