bluuebunny/crossref_metadata_2025 huggingface dataset:
The extracellular vesicles‐derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine
Authors: Nooshabadi Vajihe Taghdiri , Mardpour Soura , Yousefi‐Ahmadipour Aliakbar , Allahverdi Amir , Izadpanah Mehrnaz , Daneshimehr Fatemeh , Ai Jafar , Banafshe Hamid R. , Ebrahimi‐Barough Somayeh
Published: January 2018

Mesenchymal stem cells (MSCs) are adult multipotent cells that due to their ability to homing to damaged tissues and differentiate into specialized cells, are remarkable cells in the field of regenerative medicine. It's suggested that the predominant mechanism of MSCs in tissue repair might be related to their paracrine activity. The utilization of MSCs for tissue repair is initially based on the differentiation ability of these cells; however now it has been revealed that only a small fraction of the transplanted MSCs actually fuse and survive in host tissues. Indeed, MSCs supply the microenvironment with the secretion of soluble trophic factors, survival signals and the release of extracellular vesicles (EVs) such as exosome. Also, the paracrine activity of EVs could mediate the cellular communication to induce cell‐differentiation/self‐renewal. Recent findings suggest that EVs released by MSCs may also be critical in the physiological function of these cells. This review provides an overview of MSC‐derived extracellular vesicles as a hopeful opportunity to advance novel cell‐free therapy strategies that might prevail over the obstacles and risks associated with the use of native or engineered stem cells. EVs are very stable; they can pass the biological barriers without rejection and can shuttle bioactive molecules from one cell to another, causing the exchange of genetic information and reprogramming of the recipient cells. Moreover, extracellular vesicles may provide therapeutic cargo for a wide range of diseases and cancer therapy.
Effect of l‐caldesmon on osteoclastogenesis in RANKL–induced RAW264.7 cells
Authors: Liou Ying‐Ming , Chan Chu‐Lung , Huang Renjian , Wang Chih‐Lueh A.
Published: January 2018

Non‐muscle caldesmon (l‐CaD) is involved in the regulation of actin cytoskeletal remodeling in the podosome formation, but its function in osteoclastogenesis remains to be determined. In this study, RANKL‐induced differentiation of RAW264.7 murine macrophages to osteoclast‐like cells (OCs) was used as a model to determine the physiological role of l‐CaD and its phosphorylation in osteoclastogenesis. Upon RANKL treatment, RAW264.7 cells undergo cell‐cell fusion into multinucleate, and TRAP‐positive large OCs with a concomitant increase of l‐CaD expression. Using gain‐ and loss‐of‐function in OC precursor cells followed by RANKL induction, we showed that the expression of l‐CaD in response to RANKL activation is an important event for osteoclastogenesis, and bone resorption. To determine the effect of l‐CaD phosphorylation in osteoclastogenesis, three decoy peptides of l‐CaD were used with, respectively, Ser‐to‐Ala mutations at the Erk‐ and Pak1‐mediated phosphorylation sites, and Ser‐to‐Asp mutation at the Erk‐mediated phosphorylation sites. Both the former two peptides competed with the C‐terminal segment of l‐CaD for F‐actin binding and accelerated formation of podosome‐like structures in RANKL‐induced OCs, while the third peptide did not significantly affect the F‐actin binding of l‐CaD, and decreased the formation of podosome‐like structures in OCs. With the experiments using dephosphorylated and phosphorylated l‐CaD mutants, we further showed that dephosphorylated l‐CaD mutant facilitated RANKL‐induced TRAP activity with an increased cell fusion index, whereas phosphorylated l‐CaD decreased the TRAP activity and cell fusion. Our findings suggested that both the level of l‐CaD expression and the extent of l‐CaD phosphorylation play a role in RANKL‐induced osteoclast differentiation.
LGA‐newborn from patients with pregestational obesity present reduced adiponectin‐mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries
Authors: Muñoz‐Muñoz Estefanía , Krause Bernardo J. , Uauy Ricardo , Casanello Paola
Published: January 2018

Maternal obesity is associated with large‐for‐gestational‐age (LGA) neonates and programming of obesity‐related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO‐dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 weeks) from uncomplicated singleton pregnancies of LGA and adequate‐for‐gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho‐AMPKαThr172, eNOS, and phospho‐eNOSSer1177 after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin‐induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin‐dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental‐endothelial responses.
MicroRNA implications in the etiopathogenesis of ankylosing spondylitis
Authors: Mohammadi Hamed , Hemmatzadeh Maryam , Babaie Farhad , Gowhari Shabgah Arezoo , Azizi Gholamreza , Hosseini Fatemeh , Majidi Jafar , Baradaran Behzad
Published: January 2018

Ankylosing spondylitis (AS) is a chronic immune‐mediated inflammatory disease that affects both axial and peripheral skeletons as well as soft tissues. Recent investigations offer that disease pathogenesis is ascribed to a complex interplay of genetic, environmental, and immunological factors. Until now, there is no appropriate method for early diagnosis of AS and the successful available therapy for AS patients stay largely undefined. MicroRNAs (miRNAs), endogenous small noncoding RNAs controlling the functions of target mRNAs and cellular processes, are present in human plasma in a stable form and have appeared as possible biomarkers for activity, pathogenesis, and prognosis of the disease. In the present review, we have tried to summarize the recent findings related to miRNAs in AS development and discuss the possible utilization of these molecules as prognostic biomarkers or important therapeutic strategies for AS. Further examinations are needed to determine the unique miRNAs signatures in AS and characterize the mechanisms mediated by miRNAs in the pathology of this disease.
Effects of bone marrow mesenchymal stem cells transfected with Ang‐1 gene on hyperoxia‐induced optic nerve injury in neonatal mice
Authors: Liu Fang‐Yu , Li Guang‐Wu , Sun Chang‐Hua , Chen Sha , Cao Jun‐Fei , Ma Qian‐Qian , Fang Sheng‐Yun
Published: January 2018

Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are stromal cells, capable of proliferating and differentiating into different types of tissues. This aims of this study is to investigate the role of BMSCs transfected with angiopoietin‐1 (Ang‐1) in optic nerve injury induced by hyperoxia in a neonatal mice model. Ang‐1 overexpression vector was constructed and used to transfect BMSCs. Reverse transcription‐quantitative polymerase chain reaction was performed to detect Ang‐1 expression in BMSCs. The hyperoxia‐induced optic nerve injury model was established. The optic nerves at 6–7 mm posterior to the eyeball were extracted, and were treated with luxol fast blue staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy to examine the effects of Ang‐1‐modified BMSCs on optic nerve injury induced by hyperoxia. The mice in the Ang‐1 + BMSCs and BMSCs groups showed remarkably improved myelin sheaths of nerve fibers compared to the hyperoxia saline group. The positive expression and integrated optic density of Ang‐1 in the Ang‐1 + BMSCs group were significantly higher compared to the air control, hyperoxia saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the diameter of axons and the thickness of myelin sheath in the air control and Ang‐1 + BMSCs groups were higher compared to the hyperoxia saline group. Our study provides evidence supporting that Ang‐1‐modified BMSCs may have preventive and therapeutic effects on hyperoxia‐induced optic nerve injury in neonatal mice.
Rab 10—a traffic controller in multiple cellular pathways and locations
Authors: Chua Christelle En Lin , Tang Bor L.
Published: January 2018

Rab GTPases are key regulators of eukaryotic membrane traffic, and their functions and activities are limited to particular intracellular transport steps and their membrane localization is by and large restricted. Some Rabs do participate in more than one transport steps, but broadly speaking, there is a clear demarcation between exocytic and endocytic Rabs. One Rab protein, Rab10, however, appears to be anomalous in this regard and has a diverse array of functions and subcellular localizations. Rab10 has been implicated in a myriad of activities ranging from polarized exocytosis and endosomal sorting in polarized cells, insulin‐dependent Glut4 transport in adipocytes, axonal growth in neurons, and endo‐phagocytic processes in macrophages. It's reported subcellular localizations include the endoplasmic reticulum (ER), Golgi/TGN, the endosomes/phagosomes and the primary cilia. In this review, we summarize and discuss the multitude of known roles of Rab10 in cellular membrane transport and the molecular players and mechanisms associated with these roles.
Frontline Science: Structural insights into Resolvin D4 actions and further metabolites via a new total organic synthesis and validation
Authors: Winkler Jeremy W , Libreros Stephania , De La Rosa Xavier , Sansbury Brian E , Norris Paul C , Chiang Nan , Fichtner David , Keyes Gregory S , Wourms Nicholas , Spite Matthew , Serhan Charles N
Published: January 2018

Local production and downstream metabolism of specialized proresolving lipid mediators (SPMs) are pivotal in regulating their biological actions during resolution of inflammation. Resolvin D4 (RvD4: 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z hexaenoic acid) is one of the more recently elucidated SPMs with complete stereochemistry biosynthesized from docosahexaenoic acid. Here, we report a new multimilligram commercial synthesis that afforded enough material for matching, validation, and further evaluation of RvD4 functions. Using LC-MS-MS profiling, RvD4 was identified at bioactive amounts in human (1 pg/mL) and mouse bone marrow (12 pg/femur and tibia). In mouse bone marrow, ischemia increased the formation of RvD4 > 37-fold (455 pg/femur and tibia). Two separate mouse ischemic injury models were used, where RvD4 reduced second organ reperfusion lung injury > 50%, demonstrating organ protection. Structure–function relationships of RvD4 demonstrated > 40% increase in neutrophil and monocyte phagocytic function in human whole blood in comparison with 2 separate trans-containing double bond isomers that were inactive. These 2 isomers were prepared by organic synthesis: 4S,5R,17S-trihydroxydocosa-6E,8E,10E,13Z,15E,19Z-hexaenoic acid (10-trans-RvD4), a natural isomer, and 4S,5R,17S-trihydroxydocosa-6E,8E,10E,13E,15E,19Z-hexaenoic acid (10,13-trans-RvD4), a rogue isomer. Compared to leukotriene B4, D-series resolvins (RvD1, RvD2, RvD3, RvD4, or RvD5) did not stimulate human neutrophil chemotaxis monitored via real-time microfluidics chambers. A novel 17-oxo-containing-RvD4 product of eicosanoid oxidoreductase was identified with human bone marrow cells. Comparison of 17-oxo-RvD4 to RvD4 demonstrated that with human leukocytes 17-oxo-RvD4 was inactive. Together, these provide commercial-scale synthesis that permitted a second independent validation of RvD4 complete stereochemical structure as well as evidence for RvD4 regulation in tissues and its stereoselective phagocyte responses.
Transformation of the gas‐phase favored O‐protomer of p‐aminobenzoic acid to its unfavored N‐protomer by ion activation in the presence of water vapor: An ion‐mobility mass spectrometry study
Authors: Xia Hanxue , Attygalle Athula B.
Published: January 2018

An ion‐mobility mass spectrometry study showed that the preferred O‐protonated form of p‐aminobenzoic in the gas phase can be converted to the thermodynamically less favored N‐protomer by in‐source collision‐induced ion activation during the ion transfer process from the atmospheric region to the first vacuum region if the humidity is high in the ion source. Upon the addition of water vapor to the nitrogen gas used to promote the solid analyte to the gas phase under helium‐plasma ionization conditions, the intensity of the ion‐mobility arrival‐time peak for the N‐protomer increased dramatically. Evidently, the ion‐activation process in the first vacuum region is able to provide the energy required to surmount the barrier to isomerize the O‐protomer to the more energetic N‐protomer. The transfer of the proton attached to the carbonyl oxygen atom of the O‐protomer to the amino group takes place by a water‐bridge mechanism. Apparently, the postionization transformations that take place during the transmission of ions from the atmospheric‐pressure ion source to the detector, via different physical compartments of low to high vacuum, play an eminent role in determining the population ratios eventually manifested at the detector.
Increased ceruloplasmin expression caused by infiltrated leukocytes, activated microglia, and astrocytes in injured female rat spinal cords
Authors: Wu Yan , Shen Lin , Wang Rui , Tang Jie , Ding Shu‐Qin , Wang Sai‐Nan , Guo Xue‐Yan , Hu Jian‐Guo , Lü He‐Zuo
Published: January 2018

Ceruloplasmin (Cp), an enzyme containing six copper atoms, has important roles in iron homeostasis and antioxidant defense. After spinal cord injury (SCI), the cellular components in the local microenvironment are very complex and include functional changes of resident cells and the infiltration of leukocytes. It has been confirmed that Cp is elevated primarily in astrocytes and to a lesser extent in macrophages following SCI in mice. However, its expression in other cell types is still not very clear. In this manuscript, we provide a sensible extension of these findings by examining this system within a female Sprague–Dawley rat model and expanding the scope of inquiry to include additional cell types. Quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that the Cp mRNA and protein in SCI tissue homogenates were quite consistent with prior publications. However, we observed that Cp was expressed not only in GFAP+ astrocytes (consistent with prior reports) but also in CD11b+ microglia, CNPase+ oligodendrocytes, NeuN+ neurons, CD45+ leukocytes, and CD68+ activated microglia/macrophages. Quantitative analysis proved that infiltrated leukocytes, activated microglia/macrophages, and astrocytes should be the major sources of increased Cp.
Recent trends in wind speed across Saudi Arabia, 1978–2013: a break in the stilling
Authors: Azorin‐Molina Cesar , Rehman Shafiqur , Guijarro Jose A. , McVicar Tim R. , Minola Lorenzo , Chen Deliang , Vicente‐Serrano Sergio M.
Published: January 2018

We analyse recent trends and variability of observed near‐surface wind speed from 19 stations across Saudi Arabia (SA) for 1978–2013. The raw wind speed data set was subject to a robust homogenization protocol, and the stations were then classified under three categories: (1) coast, (2) inland and (3) mountain stations. The results reveal a statistically significant (p < 0.05) reduction of wind speed of −0.058 m s−1 dec−1 at annual scale across SA, with decreases in winter (−0.100 m s−1 dec−1) and spring (−0.066 m s−1 dec−1) also detected, being non‐significant in summer and autumn. The coast, inland and mountain series showed similar magnitude and significance of the declining trends across all SA series, except for summer when a decoupled variability and opposite trends of wind speed between the coast and inland series (significant declines: −0.101 m s−1 dec−1 and −0.065 m s−1 dec−1, respectively) and the high‐elevation mountain series (significant increase: +0.041 m s−1 dec−1) were observed. Even though wind speed declines dominated across much of the country throughout the year, only a small number of stations showed statistically significant negative trends in summer and autumn. Most interestingly, a break in the stilling was observed in the last 12‐year (2002–2013) period (+0.057 m s−1 dec−1; not significant) compared to the significant slowdown detected in the previous 24‐year (1978–2001) period (−0.089 m s−1 dec−1). This break in the slowdown of winds, even followed by a non‐significant recovery trend, occurred in all seasons (and months) except for some winter months. Atmospheric circulation plays a key role in explaining the variability of winds, with the North Atlantic Oscillation positively affecting the annual wind speed, the Southern Oscillation displaying a significant negative relationship with winds in winter, spring and autumn, and the Eastern Atlantic negatively modulating winds in summer.
Characterization and differentiation of sheep's milk from Greek breeds based on physicochemical parameters, fatty acid composition and volatile profile
Authors: Gatzias Ilias S , Karabagias Ioannis K , Kontakos Stavros P , Kontominas Michael G , Badeka Anastasia V
Published: January 2018

BACKGROUND

There are only limited studies in the literature attempting to differentiate sheep's milk originating from different sheep breeds. In the present study the physicochemical parameters (pH, percent fat, percent protein, percent lactose and percent total solids), fatty acid composition and volatile profile of raw milk from four autochthonous Greek breeds (Karagouniko, Mpoutsiko, Artas and Chios) were determined. The objective of the present study was to characterize and differentiate the sheep breeds based on the above analytical parameters in combination with chemometrics.

RESULTS

The overall correct classification rate was 79.7%%, 84.4% and 100% based on physicochemical parameters, fatty acid composition and volatile profile, respectively. Volatiles proved to be the most effective of parameters analyzed for the differentiation of sheep breed. Furthermore, the combination of physicochemical parameters and fatty acid composition gave a correct classification rate equal to 96.9%.

CONCLUSION

Either volatile profile or the combination of physicochemical parameters and fatty acid composition may be easily determined and used for the differentiation of sheep's milk from four different Greek breeds, this being the novelty of the present work. This may be very important in terms of PDO (Protected Designation of Origin) and PGI (Protected Geographical Indication) products related to specific geographical origin and sensory characteristics. © 2018 Society of Chemical Industry
Space, function, and vitality in historic areas: The tourismification process and spatial order of Shichahai in Beijing
Authors: Wang Fang , Li Jianing , Yu Fengyao , He Hao , Zhen Feng
Published: January 2018

In the development of historic areas, functions change following socioeconomic transformation. Nowadays, tourism is popular in historic areas. We examined this to understand the internal motivation, spatial logic, and functional transformation of a historic area to sustainably maintain its vitality. For Shichahai in Beijing, the selected study area, space syntax and kernel density analyses were conducted to understand the development vitality and determine the inner order of space and function in tourism development. The results clarified the inertia retained by historic genes to provide vitality in tourism.
How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal Imaging and Clinical Implications
Authors: Mottet Nicolas , Chaussy Yann , Auber Frederic , Guimiot Fabien , Arbez‐Gindre Francine , Riethmuller Didier , Cretolle Célia , Benachi Alexandra
Published: January 2018

The estimated prevalence of fetal caudal dysgenesis is 1 per 100,000 births. The functional prognosis of sacral agenesis is dominated by the large spectrum of associated caudal malformations. Except for cases associated with hydrocephalus secondary to open spinal dysraphism or chromosomal anomalies, association with mental deficiency is rare. We propose a systematic prenatal approach to cases of fetal sacral agenesis based on 9 etiologic items: clinical context, type of sacral dysgenesis, associated spinal cord malformations, mobility of lower limbs, investigation of the presacral region, analysis of the gastrointestinal tract, analysis of the genitourinary tract, associated vertebral defects, and cytogenetic analysis.
Grass and maize vegetation systems restore saline‐sodic soils in the Songnen Plain of northeast China
Authors: Luo Shasha , Tian Lei , Chang Chunling , Wang Shaojie , Zhang Jianfeng , Zhou Xue , Li Xiujun , Tran Lam‐Son Phan , Tian Chunjie
Published: January 2018

Establishment of an appropriate vegetation system for reclamation of saline‐sodic soils requires studies for specific salt‐affected region(s). The phytoremediation of saline‐sodic soils has not been well documented in the Songnen Plain of northeast China. Thus, in this study, we aimed to investigate the effects of grass (G) and maize (Zea maysL.; M) vegetation systems, which were established for 5 years, on soil properties of 10 typical saline‐sodic sampling sites across the Songnen Plain, in comparison with respective nonvegetated areas that were used as controls (CK) for the evaluation of variability among the sampling sites. Physicochemical properties, such as soil moisture, bulk density, porosity, saturated hydraulic conductivity, aggregate stability, pH, electric conductivity, total salt, organic C, total N, and C/N ratio, were analyzed. G and M vegetation significantly produced a 108% and 153% improvement in soil quality, respectively. Additionally, metagenomic analysis of the soil bacterial community revealed that vegetation enhanced the ability of the bacteria to survive in saline‐sodic soils, relative to the control. The composition of the bacterial community was highly correlated with all of the soil physicochemical properties. G vegetation had better effects than M vegetation in enhancing soil organic C, total N and aggregate stability, whereas M vegetation more favorably adjusted soil pH, physical structure, and bacterial community than G vegetation did. Collectively, these findings demonstrate that M vegetation has a greater impact than G vegetation on repairing saline‐sodic soils in the Songnen Plain of northeast China.
Wait‐list mortality of young patients with Biliary atresia: Competing risk analysis of a eurotransplant registry–based cohort
Authors: van der Doef Hubert P. J. , van Rheenen Patrick F. , van Rosmalen Marieke , Rogiers Xavier , Verkade Henkjan J. ,   for pediatric liver transplantation centers of Eurotransplant
Published: January 2018

Liver transplantation (LT) is the standard treatment for biliary atresia (BA) patients with end‐stage liver disease. The prognosis after LT has steadily improved, but overall prognosis of BA patients is also determined by mortality before LT. We aimed to quantify mortality in young BA patients on the Eurotransplant waiting list and to determine the effect of disease severity and age at time of listing on pretransplant mortality. We used a cohort study design, which incorporated data from the Eurotransplant registry. Participants were 711 BA patients who were below 5 years of age from 5 countries and listed for LT between 2001 and 2014. We applied a competing risk analysis to evaluate simultaneously the outcomes death, LT, and still waiting for a suitable organ. We used Cox proportional hazards regression to assess 2‐year mortality. In a subcohort of 416 children, we performed multivariate analyses between 2‐year mortality and disease severity or age, each at listing. Disease severity at listing was quantified by the Model for End‐Stage Liver Disease (MELD) score, which assesses bilirubin, creatinine, albumin, and international normalized ratio as continuous variables. Two‐year wait‐list mortality was 7.9%. Age below 6 months and MELD score above 20 points, each at listing, were strongly and independently associated with 2‐year mortality (each P < 0.001). A total of 21% of infants who fulfilled both criteria did not survive the first 6 months on the waiting list. In conclusion, our findings quantify mortality among young BA patients on the waiting list and the relative importance of risk factors (age and severity of disease at listing). Our results provide both an evidence base to rationally address high mortality in subgroups and a methodology to assess effects of implemented changes, for example, in allocation rules. Liver Transplantation 24 810–819 2018 AASLD.
Biophotonics of Native Silk Fibrils
Authors: Shimanovich Ulyana , Pinotsi Dorothea , Shimanovich Klimentiy , Yu Na , Bolisetty Sreenath , Adamcik Jozef , Mezzenga Raffaele , Charmet Jerome , Vollrath Fritz , Gazit Ehud , Dobson Christopher M. , Schierle Gabriele Kaminski , Holland Chris , Kaminski Clemens F. , Knowles Tuomas P. J.
Published: January 2018

Native silk fibroin (NSF) is a unique biomaterial with extraordinary mechanical and biochemical properties. These key characteristics are directly associated with the physical transformation of unstructured, soluble NSF into highly organized nano‐ and microscale fibrils rich in β‐sheet content. Here, it is shown that this NSF fibrillation process is accompanied by the development of intrinsic fluorescence in the visible range, upon near‐UV excitation, a phenomenon that has not been investigated in detail to date. Here, the optical and fluorescence characteristics of NSF fibrils are probed and a route for potential applications in the field of self‐assembled optically active biomaterials and systems is explored. In particular, it is demonstrated that NSF can be structured into autofluorescent microcapsules with a controllable level of β‐sheet content and fluorescence properties. Furthermore, a facile and efficient fabrication route that permits arbitrary patterns of NSF microcapsules to be deposited on substrates under ambient conditions is shown. The resulting fluorescent NSF patterns display a high level of photostability. These results demonstrate the potential of using native silk as a new class of biocompatible photonic material.
Tox21 Enricher: Web‐based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform
Authors: Hur Junguk , Danes Larson , Hsieh Jui‐Hua , McGregor Brett , Krout Dakota , Auerbach Scott
Published: January 2018

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human‐relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high‐throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration‐response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web‐based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over‐represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set.
The existence of periodic solutions for nonlinear beam equations on by a para‐differential method
Authors: Chen Bochao , Li Yong , Gao Yixian
Published: January 2018

This paper focuses on the construction of periodic solutions of nonlinear beam equations on the d‐dimensional tori. For a large set of frequencies, we demonstrate that an equivalent form of the nonlinear equations can be obtained by a para‐differential conjugation. Given the nonresonant conditions on each finite dimensional subspaces, it is shown that the periodic solutions can be constructed for the block diagonal equation by a classical iteration scheme.
Multiset topology via DNA and RNA mutation
Authors: El‐Sharkasy M. M. , Fouda Wafaa M. , Badr Mohamed S.
Published: January 2018

Topology is the most important branch of modern mathematics, which plays an important role in applications. In this paper, we use the concept of the topology, based on the concept of multiset to solve an important problems in life (DNA and RNA mutation) to detect diseases and help biologists in the treatment of diseases. Also, we introduce a new theory that explains if there is an existence of a mutation or not, and we have a set of metric functions through which we examine the congruence and similarity and dissimilarity between “types,” which may be a strings of bits, vectors, DNA or RNA sequences, …, etc. Finally, we will introduce a theory that which can be used to know the existence and place of mutation.
Invariant solutions for nonlinear models of illiquid markets
Authors: Fedorov Vladimir E. , Dyshaev Mikhail M.
Published: January 2018

A general nonlinear model of illiquid markets with feedback effects is considered. This equation with 2 free functional parameters contains as partial cases the classical Black‐Scholes equation, Schönbucher‐Wilmott equation, and Sircar‐Papanicolaou equation of option pricing. We obtain here the complete group classification of the equation, and for every parameters specification we obtain the principal Lie algebra and its optimal system of 1‐dimensional subalgerbras. For every such subalgebra we calculate the invariant submodel and invariant solution, when it is possible. Thus, the series of invariant submodels and invariant solutions are derived for the considered nonlinear model.
A Phytol‐Enriched Diet Activates PPAR‐α in the Liver and Brown Adipose Tissue to Ameliorate Obesity‐Induced Metabolic Abnormalities
Authors: An Ji‐Yeong , Jheng Huei‐Fen , Nagai Hiroyuki , Sanada Kohei , Takahashi Haruya , Iwase Mari , Watanabe Natsumi , Kim Young‐Il , Teraminami Aki , Takahashi Nobuyuki , Nakata Rieko , Inoue Hiroyasu , Seno Shigeto , Mastuda Hideo , Kawada Teruo , Goto Tsuyoshi
Published: January 2018

Scope

Peroxisome proliferator‐activated receptor alpha (PPAR‐α) is a ligand‐activated transcription factor that regulates lipid and carbohydrate metabolism. We investigate the effects of naturally occurring PPAR‐α agonists, phytol, and its metabolite phytanic acid, on obesity‐induced metabolic disorders using a mouse model.

Methods and results

A luciferase reporter assay shows that phytanic acid potently activates PPAR‐α among PPAR subtypes. In high‐fat‐diet‐induced, severely obese mice, a phytol‐enriched diet increases phytanic acid levels in the liver and adipose tissue, where PPAR‐α is abundantly expressed. A phytol‐enriched diet ameliorates severe obesity and the related metabolic abnormalities of white adipose tissue. Moreover, the expression of PPAR‐α target genes in the liver and brown adipose tissue is enhanced by a phytol‐enriched diet, suggesting that phytol and phytanic acid activate PPAR‐α in these organs. We confirm that phytanic acid treatment induced PPAR‐α target gene expression in both primary hepatocytes and brown adipocytes from wild‐type mice, but not in these cells from PPAR‐α‐deficient mice.

Conclusion

A phytol‐enriched diet may increase phytanic acid levels in the liver and brown adipocytes, thereby activating PPAR‐α in these organs and ameliorating obesity‐induced metabolic diseases.
Dairy Protein Supplementation Modulates the Human Skeletal Muscle microRNA Response to Lower Limb Immobilization
Authors: D'Souza Randall F. , Zeng Nina , Figueiredo Vandre C. , Markworth James F. , Durainayagam Brenan R. , Mitchell Sarah M. , Fanning Aaron C. , Poppitt Sally D. , Cameron‐Smith David , Mitchell Cameron J.
Published: January 2018

Limb immobilization results in a rapid loss of muscle size and strength. The resultant alterations in signaling pathways governing myogenesis, catabolism, and mitochondrial biogenesis are likely to include posttranscriptional regulation mediated by altered microRNAs (miRNAs). Given that protein ingestion exerts an anabolic action and may act as a countermeasure to mitigate muscle loss with immobilization, it is important to examine miRNA in this context. The objective of the study is therefore to characterize the vastus lateralis miRNA response to 14 days of disuse in males (45–60 years) randomized to receive supplementation with 20 g d−1 of dairy protein (n = 12) or isocaloric carbohydrate placebo (n = 13). Biopsies are collected before and after a 2‐week immobilization period. Of the 24 miRNAs previously identified in myogenic regulation, seven (miR‐133a, −206, −15a, −451a, −126, −208b, and let‐7e) are increased with immobilization irrespective of group; five (miR‐16, −494, let‐7a, −7c, and 7d) increased only in the carbohydrate group; and eight (miR‐1, −486, −23a, −23b, −26a, −148b, let‐7b, and −7g) are divergently expressed between groups (suppressed with protein). The ability of protein supplementation to differentially regulate miRNAs involved in key muscle regulatory pathways following short‐term limb immobilization reflects potential protective function in mitigating muscle loss during limb immobilization.
Guided undersampling classification for automated radiation therapy quality assurance of prostate cancer treatment
Authors: Brown W. Eric , Sung Kisuk , Aleman Dionne M. , Moreno‐Centeno Erick , Purdie Thomas G. , McIntosh Chris J.
Published: January 2018

Purpose

To test the use of well‐studied and widely used classification methods alongside newly developed data‐filtering techniques specifically designed for imbalanced‐data classification in order to demonstrate proof of principle for an automated radiation therapy (RT) quality assurance process on prostate cancer treatment.

Methods

A series of acceptable (majority class, n = 61) and erroneous (minority class, n = 12) RT plans as well as a disjoint set of acceptable plans used to develop features (n = 273) were used to develop a dataset for testing. A series of five widely used imbalanced‐data classification algorithms were tested with a modularized guided undersampling procedure that includes ensemble‐outlier filtering and normalized‐cut sampling.

Results

Hybrid methods including either ensemble‐outlier filtering or both filtering and normalized‐cut sampling yielded the strongest performance in identifying unacceptable treatment plans. Specifically, five methods demonstrated superior performance in both area under the receiver operating characteristics curve and false positive rate when the true positive rate is equal to one. Furthermore, ensemble‐outlier filtering significantly improved results in all but one hybrid method (p < 0.01). Finally, ensemble‐outlier filtering methods identified four minority instances that were considered outliers in over 96% of cross‐validation iterations. Such instances may be considered distinct planning errors and merit additional inspection, providing potential areas of improvement for the planning process.

Conclusions

Traditional imbalanced‐data classification methods combined with ensemble‐outlier filtering and normalized‐cut sampling provide a powerful framework for identifying erroneous RT treatment plans. The proposed methodology yielded strong classification performance and identified problematic instances with high accuracy.
Multimodal assessment of orbital immune cell infiltration and tissue remodeling during development of graves disease by 1H19F MRI
Authors: Flögel Ulrich , Schlüter Anke , Jacoby Christoph , Temme Sebastian , Banga J. Paul , Eckstein Anja , Schrader Jürgen , Berchner‐Pfannschmidt Utta
Published: January 2018

Purpose

To evaluate key molecular and cellular features of Graves orbitopathy (GO) by simultaneous monitoring of alterations in morphology, inflammatory patterns, and tissue remodeling.

Methods

To this end, we utilized a murine model of GO induced by immunization with a human thyroid‐stimulating hormone receptor A‐subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl) immunized with β‐galactasidose plasmid. From these, 17 GO and 12 Ctrl mice were subjected to multimodal MRI at 9.4T, whereas 23 mice only underwent histology. Beyond anatomical hydrogen‐1 (1H) MRI, we employed transverse relaxation time (T2) mapping for visualization of edema, chemical exchange saturation transfer (CEST) for detection of hyaluronan, and fluorine‐19 (19F) MRI for tracking of in situ‐labeled immune cells after intravenous injection of perfluorcarbons (PFCs).

Results

1H/19F MRI demonstrated substantial infiltration of PFC‐loaded immune cells in peri and retro‐orbital regions of GO mice, whereas healthy Ctrls showed only minor 19F signals. In parallel, T2 mapping indicated onset of edema in periorbital tissue and adjacent ocular glands (P = 0.038/0.017), which were associated with enhanced orbital CEST signals in GO mice (P = 0.031). Concomitantly, a moderate expansion of retrobulbar fat (P = 0.029) was apparent; however, no signs for extraocular myopathy were detectable. 19F MRI‐based visualization of orbital inflammation exhibited the highest significance level to discriminate between GO and Ctrl mice (P = 0.006) and showed the best correlation with the clinical score (P = 0.0007).

Conclusion

The present approach permits the comprehensive characterization of orbital tissue and holds the potential for accurate GO diagnosis in the clinical setting. Magn Reson Med 80:711–718, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
A framework for implementation of RVE‐based multiscale models in computational homogenization using isogeometric analysis
Authors: Alberdi Ryan , Zhang Guodong , Khandelwal Kapil
Published: January 2018

This study presents an isogeometric framework for incorporating representative volume element–based multiscale models into computational homogenization. First‐order finite deformation homogenization theory is derived within the framework of the method of multiscale virtual power, and Lagrange multipliers are used to illustrate the effects of considering different kinematical constraints. Using a Lagrange multiplier approach in the numerical implementation of the discrete system naturally leads to a consolidated treatment of the commonly employed representative volume element boundary conditions. Implementation of finite deformation computational strain‐driven, stress‐driven, and mixed homogenization is detailed in the context of isogeometric analysis (IGA), and performance is compared to standard finite element analysis. As finite deformations are considered, a numerical multiscale stability analysis procedure is also detailed for use with IGA. Unique implementation aspects that arise when computational homogenization is performed using IGA are discussed, and the developed framework is applied to a complex curved microstructure representing an architectured material.
Is high‐grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies
Authors: Tolkach Yuri , Kristiansen Glen
Published: January 2018

High‐grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a comparative molecular genetic characterisation of HGPIN and its corresponding carcinoma to study this transformation. However, to date, some HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde colonisation of the prostatic acini in an HGPIN‐like manner, have been described. In this work, we hypothesise that the lesion formerly known as HGPIN adjacent to invasive carcinoma does not necessarily represent its respective precursor lesion. This hypothesis stems from recent morphological, experimental, and theoretical evidence on the development of tumour clonality, as well as recent studies outlining the three‐dimensional architecture of prostate adenocarcinomas (most importantly, their interconnection with the tumoural glandular system). Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Critical role of rabphilin‐3A in the pathophysiology of experimental lymphocytic neurohypophysitis
Authors: Yasuda Yoshinori , Iwama Shintaro , Kiyota Atsushi , Izumida Hisakazu , Nakashima Kohtaro , Iwata Naoko , Ito Yoshihiro , Morishita Yoshiaki , Goto Motomitsu , Suga Hidetaka , Banno Ryoichi , Enomoto Atsushi , Takahashi Masahide , Arima Hiroshi , Sugimura Yoshihisa
Published: January 2018

Autoimmune hypophysitis (AH) is thought to be an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland. Among AH pathologies, lymphocytic infundibulo‐neurohypophysitis (LINH) involves infiltration of the neurohypophysis and/or the hypothalamic infundibulum, causing central diabetes insipidus resulting from insufficiency of arginine vasopressin secretion. The pathophysiological and pathogenetic mechanisms underlying LINH are largely unknown. Clinically, differentiating LINH from other pituitary diseases accompanied by mass lesions, including tumours, has often been difficult, because of similar clinical manifestations. We recently reported that rabphilin‐3A is an autoantigen and that anti‐rabphilin‐3A antibodies constitute a possible diagnostic marker for LINH. However, the involvement of rabphilin‐3A in the pathogenesis of LINH remains to be elucidated. This study was undertaken to explore the role of rabphilin‐3A in lymphocytic neurohypophysitis and to investigate the mechanism. We found that immunization of mice with rabphilin‐3A led to neurohypophysitis. Lymphocytic infiltration was observed in the neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice immunized with rabphilin‐3A showed an increase in the volume of urine that was hypotonic as compared with control mice. Administration of a cocktail of monoclonal anti‐rabphilin‐3A antibodies did not induce neurohypophysitis. However, abatacept, which is a chimeric protein that suppresses T‐cell activation, decreased the number of T cells specific for rabphilin‐3A in peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic infiltration of CD3+ T cells in the neurohypophysis of mice that had been immunized with rabphilin‐3A. Additionally, there was a linear association between the number of T cells specific for rabphilin‐3A in PBMCs and the number of CD3+ T cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin‐3A is a pathogenic antigen, and that T cells specific for rabphilin‐3A are involved in the pathogenesis of neurohypophysitis in mice. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mixtures of antidepressant amphiphilic drug imipramine hydrochloride and anionic surfactant: Micellar and thermodynamic investigation
Authors: Khan Farah , Rub Malik Abdul , Azum Naved , Asiri Abdullah M.
Published: January 2018

Aggregation as well as thermodynamic behavior of amphiphilic imipramine hydrochloride (IMH) drug (antidepressant) and anionic surfactant (sodium dodecyl sulfate [NaDS] as well as sodium dodecylbenzenesulfonate [NaDBS]) mixtures as a function of solution composition in aqueous solutions have been evaluated by conductometry method at different temperatures. Surfactant (NaDS and NaDBS) employed in the current study is anionic in nature. Various theoretical models such as Clint, Rubingh, Motomura, and Rodenas were employed to gain information regarding the type of interaction between the components in the solution mixtures. The value of micellar mole fraction evaluated by different utilized models is found to be more for IMH‐NaDBS mixtures in comparison with IMH‐NaDS mixtures, signifying that participation of NaDBS is more in mixed micelles as compared with NaDS. Owing to the different charge of employed drug and surfactant, which sources high synergistic results in the mixed system comparative to the possessions of their pure compounds, means here anionic surfactants were elected in favor of the quantitation of cationic drug. The value of interaction parameters (β) was also evaluated by employing the Rubingh's model. The values of Gibbs free energy (∆G0m) for all systems attained to be negative in all studied systems showing that the systems are spontaneous in nature.
Influence of Stoichiometry on the Thrust and Heat Deposition of On‐Chip Nanothermites
Authors: Ramachandran Raghav , Vuppuluri Vasant S. , Fleck Trevor J. , Rhoads Jeffrey F. , Gunduz Ibrahim E. , Son Steven F.
Published: January 2018

Currently, there is very little systematic work quantifying the thrust or heat applied to an electronic circuit or other substrate by a deposited layer of energetic material. A better understanding of the interactions between nanoscale energetic materials and electronic systems, as a function of stoichiometry, is needed. For this purpose, formulations of nAl‐CuO and nAl‐Bi2O3 nanothermites were prepared at different equivalence ratios and selectively deposited onto electronic circuit analogues (silicon wafers) and the amounts of thrust production and heat deposition were measured. Both nanothermite systems produced maximum thrust near stoichiometric ratios, accompanied by a shock wave, with minimal thermal effects due to large gas production, which ejects the hot products of the substrates. Conversely, more fuel‐rich mixtures led to significantly decreased thrust while increasing heat deposition due to the lower gas production, which allowed more heat to diffuse to the substrates. This shows that the energetic material response can be tuned between thrust or heat deposition by just varying the equivalence ratio. The conductive heat transfer within the silicon substrates from the nAl‐CuO system increased more than the nAl‐Bi2O3 system at fuel rich conditions due to its higher heat of combustion.