bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cleavage of caspase‐12 at Asp94, mediated by endoplasmic reticulum stress (ERS), contributes to stretch‐induced apoptosis of myoblasts
Authors: Song Jing , Zhang Qiang , Wang Shuai , Yang Fang , Chen Zhenggang , Dong Quanjiang , Ji Qiuxia , Yuan Xiao , Ren Dapeng 
Published: June 2018

Mechanical overloading can lead to skeletal muscle damage instead of remodeling. This is attributed to the excessive apoptosis of myoblasts, mechanism of which remains to be elucidated. The present study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) and caspase‐12 in mediating the stretch‐induced apoptosis of myoblasts. Myoblast apoptosis was evaluated by Hoechst staining, DNA fragmentation assay, Annexin V binding, and propidium iodide staining, as well as caspase‐3 and poly‐ADP‐ribose polymerase 1 cleavage. First, our results showed that apoptosis was elevated in a time‐dependent manner when myoblasts were subjected to cyclic mechanical stretch (CMS) for 12, 24, and 36 hr. Concomitantly, CMS triggered the ERS and caspase‐12 cleavage; ERS inhibitor GSK 2606414 suppressed the CMS‐induced cleavage of caspase‐12 and myoblast apoptosis. Silencing caspase‐12 attenuated the apoptosis of myoblasts under CMS. Furthermore, CMS‐induced myoblast apoptosis was partially recovered by overexpressing wild‐type caspase‐12 in caspase‐12‐silenced myoblasts. In contrast, overexpressing mutant caspase‐12 (D94N), which cannot be cleaved into the active caspase‐12 fragments, failed to accomplish the same effect. Finally, C2C12 overexpressing truncated caspase‐12 segment (TC‐casp12‐D94), which starts from Asp94 and ends at Asn419, underwent apoptosis under both static and stretched conditions. Interestingly, C2C12 myoblasts seemed to be resistant to stretch‐induced apoptosis upon low‐serum‐induced differentiation. In conclusion, our study provided evidence that caspase‐12 cleavage at Asp94, induced by ERS under mechanical stimuli, is the key molecule in initiating the stretch‐triggered apoptosis of myoblasts.
BMAL1 and CLOCK proteins in regulating UVB‐induced apoptosis and DNA damage responses in human keratinocytes
Authors: Sun Yang , Wang Peiling , Li Hongyu , Dai Jun 
Published: June 2018

A diverse array of biological processes are under circadian controls. In mouse skin, ultraviolet ray (UVR)‐induced apoptosis and DNA damage responses are time‐of‐day dependent, which are controlled by core clock proteins. This study investigates the roles of clock proteins in regulating UVB responses in human keratinocytes (HKCs). We found that the messenger RNA expression of brain and muscle ARNT‐like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) genes is altered by low doses (5 mJ/cm2) of UVB in the immortalized HaCat HKCs cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation of Rad3‐related protein kinases–checkpoint kinase 1–p53 mediated DNA damage checkpoints, it leads to suppression of UVB‐stimulated apoptotic responses, and downregulation of UVB‐elevated expression of DNA damage marker γ‐H2AX and cell cycle inhibitor p21. Diminished apoptotic responses are also observed in primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK depletion shows a suppressive effect on UVB‐induced p53 protein accumulation, depletion of either clock gene triggers early keratinocyte differentiation of HKCs at their steady state. These results suggest that UVB‐induced apoptosis and DNA damage responses are controlled by clock proteins, but via different mechanisms in the immortalized human adult low calcium temperature and primary HKCs. Given the implication of UVB in photoaging and photocarcinogenesis, mechanistic elucidation of circadian controls on UVB effects in human skin will be critical and beneficial for prevention and treatment of skin cancers and other skin‐related diseases.
P2Y12 shRNA treatment decreases SGC activation to relieve diabetic neuropathic pain in type 2 diabetes mellitus rats
Authors: Wang Shouyu , Wang Zilin , Li Lin , Zou Lifang , Gong Yingxin , Jia Tianyu , Zhao Shanhong , Yuan Huilong , Shi Liran , Liu Shuangmei , Wu Bing , Yi Zhihua , Liu Hui , Gao Yun , Li Guilin , Deussing Jan M. , Li Man , Zhang Chunping , Liang Shangdong 
Published: June 2018

Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus (DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in neuropathic pain through the release of proinflammatory cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our aim was to investigate the role of the P2Y12 receptor on the pathological changes in diabetic neuropathic pain. The present study showed that diabetic neuropathic pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The results showed that the expression levels of P2Y12 messenger RNA (mRNA) and protein in DRG SGCs were increased in DM model rats compared with control rats. Glial fibrillary acidic protein (GFAP) and interleukin‐1β (IL‐1β) expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA (shRNA) decreased the upregulated expression of P2Y12 mRNA and protein, coexpression of P2Y12 and GFAP, the expression of GFAP, IL‐1β, and tumor necrosis factor‐receptor 1 in the DRG of DM rats, and relieved mechanical and thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA, the enhancing integrated OPTICAL density (IOD) ratios of p‐P38 MAPK to P38 mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA were significantly lower than that in the untreated DM rats. Therefore, P2Y12 shRNA treatment decreased SGC activation to relieve mechanical and thermal hyperalgesia in DM rats.
Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease
Authors: Gouzi Fares , Blaquière Marine , Catteau Matthias , Bughin François , Maury Jonathan , Passerieux Emilie , Ayoub Bronia , Mercier Jacques , Hayot Maurice , Pomiès Pascal 
Published: June 2018

The proteolytic autophagy pathway is enhanced in the lower limb muscles of patients with chronic obstructive pulmonary disease (COPD). Reactive oxygen species (ROS) have been shown to regulate autophagy in the skeletal muscles, but the role of oxidative stress in the muscle autophagy of patients with COPD is unknown. We used cultured myoblasts and myotubes from the quadriceps of eight healthy subjects and twelve patients with COPD (FEV1% predicted: 102.0% and 32.0%, respectively; p < 0.0001). We compared the autophagosome formation, the expression of autophagy markers, and the autophagic flux in healthy subjects and the patients with COPD, and we evaluated the effects of the 3‐methyladenine (3‐MA) autophagy inhibitor on the atrophy of COPD myotubes. Autophagy was also assessed in COPD myotubes treated with an antioxidant molecule, ascorbic acid. Autophagosome formation was increased in COPD myoblasts and myotubes (p = 0.011; p < 0.001), and the LC3 2/LC3 1 ratio (p = 0.002), SQSTM1 mRNA and protein expression (p = 0.023; p = 0.007), BNIP3 expression (p = 0.031), and autophagic flux (p = 0.002) were higher in COPD myoblasts. Inhibition of autophagy with 3‐MA increased the COPD myotube diameter (p < 0.001) to a level similar to the diameter of healthy subject myotubes. Treatment of COPD myotubes with ascorbic acid decreased ROS concentration (p < 0.001), ROS‐induced protein carbonylation (p = 0.019), the LC3 2/LC3 1 ratio (p = 0.037), the expression of SQSTM1 (p < 0.001) and BNIP3 (p < 0.001), and increased the COPD myotube diameter (p < 0.001). Thus, autophagy signaling is enhanced in cultured COPD muscle cells. Furthermore, the oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.
Enhancing developmental rate and quality of mouse single blastomeres into blastocysts using a microplatform
Authors: Yekani Farshid , Fazel‐Tabar Mohammad , Kowsari‐Esfahan Reza , Renaud Philippe , Kavand Hanieh , Esfandiari Fereshteh , Azarnia Mahnaz , Montazeri Leila , Baharvand Hossein 
Published: June 2018

The present work reports the beneficial effects of using a microplatform on the development of mouse single blastomeres (SBs) to the blastocyst stage. Development of blastocysts from SBs separated from two‐ and four‐cell stage embryos (two‐ and four‐cell SBs) can provide a valuable supply both for couples who use fertility‐assisted techniques and farm animals. As a step forward, we introduce three chips that provide the possibility of culturing SBs separately, in groups, and in the vicinity of the intact embryo (co‐culture), while each well of the chips is assigned to an isolated SB. Two‐ and four‐cell SBs co‐cultured with intact embryos showed 97.1% and 76.6% developmental rates and up to 34.1% and 49.1% growth relative to the microdroplet method (control). We examined the quality of developed blastocysts by assessing the total cell number, the number of inner cell mass (ICM) according to the octamer‐binding transcription factor 4 marker (OCT4), and trophectoderm (TE). Co‐culture of SBs with an intact embryo in a chip with nanoscale culture medium volume also increased the cell population of the developed embryo. The ICM:TE ratio, which is the most important blastocyst quality parameter, also indicated that developed two‐cell SBs have a higher degree of similarity to intact embryos despite fewer numbers of total cells.
Colors of attraction: Modeling insect flight to light behavior
Authors: Donners Maurice , van Grunsven Roy H.A. , Groenendijk Dick , van Langevelde Frank , Bikker Jan Willem , Longcore Travis , Veenendaal Elmar 
Published: June 2018

AbstractLight sources attract nocturnal flying insects, but some lamps attract more insects than others. The relation between the properties of a light source and the number of attracted insects is, however, poorly understood. We developed a model to quantify the attractiveness of light sources based on the spectral output. This model is fitted using data from field experiments that compare a large number of different light sources. We validated this model using two additional datasets, one for all insects and one excluding the numerous Diptera. Our model facilitates the development and application of light sources that attract fewer insects without the need for extensive field tests and it can be used to correct for spectral composition when formulating hypotheses on the ecological impact of artificial light. In addition, we present a tool allowing the conversion of the spectral output of light sources to their relative insect attraction based on this model.
Filter‐based emulsification microextraction as an efficient method for the determination of chlorophenols by gas chromatography
Authors: Bazregar Mohammad , Rajabi Maryam , Yamini Yadollah , Asghari Alireza 
Published: June 2018

AbstractIn this work, an efficient microextraction method was applied for the extraction of some chlorophenols in water samples. This method, termed filter‐based emulsification microextraction, is based on the dispersion of an extractant into an aqueous sample solution to accelerate the extraction process and the utilization of a Nylon syringe filter to break the emulsion. After phase separation, the method is coupled with gas chromatography as a final analyzer instrument. The overall derivatization/extraction time was about 90 s. The proposed method is centrifuge‐free, and it also provides a suitable sample clean‐up by filtration of the extracting phase. The effective parameters involved in the extraction method were optimized. Under the optimal experimental conditions, the method provided a good linearity in the range of 2.0–2000 ng/mL, extraction repeatabilities (relative standard deviations) below 9.4%, enrichment factors of 180–203, and limits of detection between 0.5 and 1.2 ng/mL.
Design of Silica‐Oligourethane‐Collagen Membranes for Inflammatory Response Modulation: Characterization and Polarization of a Macrophage Cell Line
Authors: Muñoz‐González Pedro U. , Rivera‐Debernardi Olivia , Mendoza‐Novelo Birzabith , Claudio‐Rizo Jesús A. , Mata‐Mata José L. , Delgadillo‐Holtfort Isabel , Carriles Ramón , Flores‐Moreno Mauricio , González‐García Gerardo , Cauich‐Rodríguez Juan V. , Delgado Jorge , Castellano Laura E. 
Published: June 2018

AbstractThe polarization of macrophages M0 to M1 or M2 using molecules embedded in matrices and hydrogels is an active field of study. The design of biomaterials capable of promoting polarization has become a paramount need nowadays, since in the healing process macrophages M1 and M2 modulate the inflammatory response. In this work, several immunocytochemistry and ELISA tests strongly suggest the achievement of polarization using collagen‐based membranes crosslinked with tri‐functionalized oligourethanes and coated with silica. Measuring the amount of TGF‐β1 secreted to culture media by macrophages growth on these materials, and quantifying the macrophage morphology, it is proved that it is possible to stimulate the anti‐inflammatory pathway toward M2, having measurements with p ≤ 0.05 of statistical significance between the control and the collagen‐based membranes. Furthermore, some physicochemical characteristics of the hybrid materials are tested envisaging future applications: collagenase degradation resistance, water uptake, collagen fiber diameter, and deformation resistance are increased for all the crosslinked biomaterials. It is considered that the biological and physicochemical properties make the material suitable for the modulation of the inflammatory response in the chronic wounds and promising for in vivo studies.
Ratings surveillance and reliability in a study of major depressive disorder with subthreshold hypomania (mixed features)
Authors: Targum Steven D. , Pendergrass J. Cara , Lee Sang , Loebel Antony 
Published: June 2018

AbstractObjectivesSite‐independent ratings surveillance assessed ratings reliability in a clinical trial.MethodsInter‐rater reliability was assessed at the screen visit in a 6‐week, double‐blind, placebo‐controlled study of lurasidone for the treatment of major depressive disorder (MDD) with subthreshold hypomanic (“mixed”) symptoms (clinicaltrials.gov NCT01421134). Site‐based Montgomery‐Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) interviews were paired with 184 site‐independent ratings derived from audio‐digital recordings.ResultsThe paired MADRS and YMRS scores were highly correlated (r = 0.708 and 0.885, respectively) and generated minimal scoring discordance. The surveillance program identified 14 MADRS scores (7.6% of this sample) that were below the study entry criterion (MADRS ≥26) and resulted in screen failure.When present, paired scoring discordance was associated with symptom severity, interview length, interview quality, and the level of patient cooperation.Higher severity scores (MADRS ≥40 and YMRS ≥15) were associated with greater paired scoring discordance. Further, MADRS scores <30 and short MADRS interviews conducted in ≤12 min revealed significantly more pairs of discordant outliers (p = 0.04 and 0.009, respectively).ConclusionsThe findings suggest that MDD patients with mixed features can be reliably assessed, that paired site‐based and site‐independent assessments were generally concordant, and that ratings surveillance may reinforce ratings precision.
Multimaterial multijoint topology optimization
Authors: Woischwill Christopher , Kim Il Yong 
Published: June 2018

SummaryIn this paper, a methodology that solves multimaterial topology optimization problems while also optimizing the quantity and type of joints between dissimilar materials is proposed. Multimaterial topology optimization has become a popular design optimization technique since the enhanced design freedom typically leads to superior solutions; however, the conventional assumption that all elements are perfectly fused together as a single piece limits the usefulness of the approach since the mutual dependency between optimal multimaterial geometry and optimal joint design is not properly accounted for. The proposed methodology uses an effective decomposition approach to both determine the optimal topology of a structure using multiple materials and the optimal joint design using multiple joint types. By decomposing the problem into two smaller subproblems, gradient‐based optimization techniques can be used and large models that cannot be solved with nongradient approaches can be solved. Moreover, since the joining interfaces are interpreted directly from multimaterial topology optimization results, the shape of the joining interfaces and the quantity of joints connecting dissimilar materials do not need to be defined a priori. Three numerical examples, which demonstrate how the methodology optimizes the geometry of a multimaterial structure for both compliance and cost of joining, are presented.
A stabilization technique for coupled convection‐diffusion‐reaction equations
Authors: Hernández H. , Massart T. J. , Peerlings R. H. J. , Geers M. G. D. 
Published: June 2018

SummaryPartial differential equations having diffusive, convective, and reactive terms appear in the modeling of a large variety of processes in several branches of science. Often, several species or components interact with each other, rendering strongly coupled systems of convection‐diffusion‐reaction equations. Exact solutions are available in extremely few cases lacking practical interest due to the simplifications made to render such equations amenable by analytical tools. Then, numerical approximation remains the best strategy for solving these problems. The properties of these systems of equations, particularly the lack of sufficient physical diffusion, cause most traditional numerical methods to fail, with the appearance of violent and nonphysical oscillations, even for the single equation case. For systems of equations, the situation is even harder due to the lack of fundamental principles guiding numerical discretization. Therefore, strategies must be developed in order to obtain physically meaningful and numerically stable approximations. Such stabilization techniques have been extensively developed for the single equation case in contrast to the multiple equations case. This paper presents a perturbation‐based stabilization technique for coupled systems of one‐dimensional convection‐diffusion‐reaction equations. Its characteristics are discussed, providing evidence of its versatility and effectiveness through a thorough assessment.
Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community‐acquired pneumonia in children: A hospital‐based study in India
Authors: Awasthi Shally , Yadav Krishna K. , Pandey Monika , Mahdi Abbas A. , Awasthi Nidhi 
Published: June 2018

AbstractBackgroundHigh morbidity and mortality due to community‐acquired pneumonia (CAP) is seen in children under 5 years of age in India. Besides identified risk factors for CAP, there may be a phenotype‐genotype association with cytokines, resulting in enhanced inflammatory response resulting in the adverse outcome (AO), namely complications and death.AimTo assess the association of IL1RA gene polymorphism on serum levels of IL1RA and with AO in children under 5 years of age hospitalized with WHO‐defined severe CAP.MethodA prospective cohort study with nested case‐control design conducted in a tertiary care teaching hospital after obtaining institutional ethical approval. Included were children between 2 and 59 months of age hospitalized with WHO‐defined severe CAP with consistent radiological abnormalities. Excluded were those with suspected or proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA test to detect serum levels of IL1RA.ResultsFrom 2014 to 2016, of 420 screened cases, 350 were eligible and included, of which 132 (37.7%) had no complication and 218 (62.3%) had AO, which included complications like empyema, pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p 0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was statistically significantly elevated in CAP with AO (2.55 ± 1.44) versus uncomplicated (0.87 ± 0.52) (P < 0.0001).ConclusionIn IL1RA gene, A1A1 genotype was associated with lower risk and A2A2 genotype with increased the risk of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating possibly enhanced inflammatory response resulting in AO of CAP.
Dating igneous rocks using the Potassium–Argon Laser Experiment (KArLE) instrument: A case study for ~380 Ma basaltic rocks
Authors: Cho Yuichiro , Cohen Barbara A. 
Published: June 2018

RationaleWe report new K–Ar isochron data for two ~380 Ma basaltic rocks, using an updated version of the Potassium–Argon Laser Experiment (KArLE), which is being developed for future in situ dating of planetary materials. These basalts have K contents comparable with those of lunar KREEP basalts or igneous lithologies found by Mars rovers, whereas previous proof‐of‐concept studies focused primarily on more K‐rich rocks. We aim to measure these analogous samples to show the advancing capability of in situ K–Ar geochronology.MethodsCombining laser‐induced breakdown spectroscopy (LIBS), mass spectrometry (MS), and microscopic analyses, we measured the abundance of K and 40Ar from 23 spots on the basalt samples. We then constructed K–Ar isochron plots from these rocks. The breadboard instrument consists of flight‐equivalent devices including a 30‐mJ Nd:YAG laser and a quadrupole mass spectrometer.ResultsDespite much lower K abundances than in previous studies, the isochron slopes yielded 380 ± 44 Ma and 398 ± 50 Ma for 380.7‐Ma and 373.5‐Ma rocks, respectively, indicating that accuracy better than 25 Ma (<7%) is achievable with our instrument. The isochron intercepts both yielded trapped 40Ar approximately 1 × 10−6 cm3 STP/g.ConclusionsOur experimental results demonstrate that accurate and precise measurements are possible using the KArLE approach on basaltic rocks, which are ubiquitous on planetary surfaces, and are useful in addressing a wide range of questions in planetary science.
Forestry crane posture estimation with a two‐dimensional laser scanner
Authors: Hyyti Heikki , Lehtola Ville V. , Visala Arto 
Published: June 2018

AbstractCrane posture estimation is the stepping stone to forest machine automation. Here, we introduce a robust minimal perception solution, that is, one that uses minimal constraints for maximal benefits. Specifically, we introduce a robust particle‐filter‐based method to estimate and track the posture of a flexible hydraulic crane by using only low‐cost equipment, namely, a two‐dimensional (2D) laser scanner, two short magnetically attached metal tubes as targets, and an angle sensor. An important feature of our method is that it incorporates control signals for hydraulic actuators. In contrast to the previous works employing laser scanners, we do not use the full shape of the crane to estimate the crane posture, but, instead, we use only two small targets in the field of view of the laser scanner. Thus, a large share of the range data is useful for other purposes, for example, to map the surrounding environment. We test the proposed method in a challenging forest environment and show that the particle filter is able to estimate the posture of the hydraulic crane efficiently and reliably in the presence of occlusions and obstructions. During our comprehensive testing, the tip position was measured with average errors smaller than 4.3 cm whereas the absolute maximum error was 15 cm.