bluuebunny/crossref_metadata_2025 huggingface dataset:
Single and population coding of taste in the gustatory cortex of awake mice
Authors: Levitan David , Lin Jian-You , Wachutka Joseph , Mukherjee Narendra , Nelson Sacha B. , Katz Donald B.
Published: July 2019

Electrophysiological analysis has revealed much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats and about how these dynamics relate to behavior. With regard to mice, however, data concerning cortical taste coding have largely been restricted to imaging, a technique that reveals average levels of neural responsiveness but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour, and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3–4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability, the latter responses emerging ~0.5 s after the former, with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses: neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomic regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not “gustotopic” but also go beyond these imaging results to show that mice process tastes through time.

NEW & NOTEWORTHY Here, we analyzed taste-related spiking activity in awake mouse gustatory cortical (GC) neural ensembles, revealing deep similarities between mouse cortical taste processing and that repeatedly demonstrated in rat: mouse GC ensembles code multiple aspects of taste in a coarse-coded, time-varying manner that is essentially invariant across the spatial extent of GC. These data demonstrate that, contrary to some reports, cortical network processing is distributed, rather than being separated out into spatial subregion.
Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue
Authors: Saxton Sophie N. , Clark Ben J. , Withers Sarah B. , Eringa Etto C. , Heagerty Anthony M.
Published: July 2019

Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.
Bone Marrow-Derived CD44+Cells Migrate to Tissue-Engineered Constructs via SDF-1/CXCR4-JNK Pathway and Aid Bone Repair
Authors: Lu Yanzhu , Xing Junchao , Yin Xiaolong , Zhu Xiaobo , Yang Aijun , Luo Jiyue , Gou Jing , Dong Shiwu , Xu Jianzhong , Hou Tianyong
Published: July 2019

Background and Aims.Host-derived cells play crucial roles in the regeneration process of tissue-engineered constructs (TECs) during the treatment of large segmental bone defects (LSBDs). However, their identity, source, and cell recruitment mechanisms remain elusive.Methods.A complex model was created using mice by combining methods of GFP+bone marrow transplantation (GFP-BMT), parabiosis (GFP+-BMT and wild-type mice), and femoral LSBD, followed by implantation of TECs or DBM scaffolds. Postoperatively, the migration of host BM cells was detected by animal imaging and immunofluorescent staining. Bone repair was evaluated by micro-CT. Signaling pathway repressors including AMD3100 and SP600125 associated with the migration of BM CD44+cells were further investigated.In vitro, transwell migration and western-blotting assays were performed to verify the related signaling pathway.In vivo, the importance of the SDF-1/CXCR4-JNK pathway was validated by ELISA, fluorescence-activated cell sorting (FACS), immunofluorescent staining, and RT-PCR.Results.First, we found that host cells recruited to facilitate TEC-mediated bone repair were derived from bone marrow and most of them express CD44, indicating the significance of CD44 in the migration of bone marrow cells towards donor MSCs. Then, the predominant roles of SDF-1/CXCR4 and downstream JNK in the migration of BM CD44+cells towards TECs were demonstrated.Conclusion.Together, we demonstrated that during bone repair promoted by TECs, BM-derived CD44+cells were essential and their migration towards TECs could be regulated by the SDF-1/CXCR4-JNK signaling pathway.
Effects of Camellia Sinensis Extract on Repeated Restraint Stress-Induced Ovariectomized Female Rats
Authors: Ye Minsook , Jang Daehyuk , Kim Jin Su , Kim Kyungsoo , Shim Insop
Published: July 2019

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.
The CuePed Trial: How Does Environmental Complexity Impact Cue Effectiveness? A Comparison of Tonic and Phasic Visual Cueing in Simple and Complex Environments in a Parkinson’s Disease Population with Freezing of Gait
Authors: Marsh Rodney , Cole Michael H. , Dissanayaka Nadeeka N. W. , Au Tiffany R. , Clewett Sandra , O’Sullivan John D. , Silburn Peter A.
Published: July 2019

Background. The optimal prescription of cueing for the treatment of freezing of gait (FoG) in Parkinson’s disease (PD) is currently a difficult problem for clinicians due to the heterogeneity of cueing modalities, devices, and the limited comparative trial evidence. There has been a rise in the development of motion-sensitive, wearable cueing devices for the treatment of FoG in PD. These devices generally produce cues after signature gait or electroencephalographic antecedents of FoG episodes are detected (phasic cues). It is not known whether these devices offer benefit over simple (tonic) cueing devices. Methods. We assembled 20 participants with PD and FoG and familiarized them with a belt-worn, laser-light cueing device (Agilitas™). The device was designed with 2 cueing modalities—gait-dependent or “phasic” cueing and gait-independent or “tonic” cueing. Participants used the device sequentially in the off, phasic, or tonic modes, across 2 tasks—a 2-minute walk and an obstacle course. Results. A significant improvement in mean distance walked during the 2-minute walk test was observed for the tonic mode (127.3 m) compared with the off (111.4 m) and phasic (116.1 m) conditions. In contrast, there was a nonsignificant trend toward improvement in FoG frequency, duration, and course time when the device was switched from off to tonic and to phasic modes for the obstacle course. Conclusions. Parkinson’s disease patients with FoG demonstrated an improvement in distance walked during the two-minute walk test when a cueing device was switched from off to phasic and to tonic modes of operation. However, this benefit was lost when patients negotiated an obstacle course.
Safety and Effectiveness of Mist Antiaris, a Herbal Preparation for Treatment of Peripheral Neuropathy
Authors: Antwi S. , Asiedu-Larbi J. , Martey O. N. K. , Quasie O. , Boakye-Yiadom M. , Ayertey F. , Yeboah R. , Sapaty C. A. , Offei-Abrokwa D. , Oduro-Mensah D. , Kumatia E. K. , Ocloo A.
Published: July 2019

Mist Antiaris is a herbal decoction for treatment of nervous disorders. Safety and efficacy were evaluated in Sprague-Dawley rats and human patients, respectively. Acute toxicity was assessed by administration of a single 5000 mg/kg oral dose of decoction to a group of six rats. For subchronic toxicity, four groups of six rats each received water (control) or 10, 100, or 200 mg/kg oral doses of decoction daily for eight weeks. Body weight, serum, urine, and hematological profile of the animals in each group were monitored over the period. Effects of treatment on pentobarbital-induced sleeping time and histology of liver, lung, heart, and kidney tissue were assessed at the end of the study. There was no evidence of acute toxicity within 48 hours of the oral dose. Over the 8-week period, body weight increases in Mist Antiaris treatment groups were reduced relative to the control group. There were no significant differences in urine profile, serum biochemistry, hematological parameters, and pentobarbital-induced sleeping time. Tissue histology revealed no differences relative to controls. Assessment of efficacy was by retrospective review of data on patients who presented with peripheral neuropathy. Treatment resulted in 53.7 % of patients reporting complete resolution and 15.7 % showing reduction in neuropathic symptoms. The data demonstrate that there is no toxicity due to subchronic administration of Mist Antiaris in Sprague-Dawley rats. The reduction or resolution of neuropathic symptoms indicated by patents’ file data provides evidence to suggest that Mist Antiaris has antineuropathic effects.
Three‐Dimensional Nonlinear Seismic Response of Immersed Tunnel in Horizontally Layered Site under Obliquely Incident SV Waves
Authors: Zhou Xiaojie , Liang Qinghua , Zhang Yueyu , Liu Zhongxian , He Ying
Published: July 2019

A three‐dimensional (3D) detailed numerical model of an immersed tunnel in a horizontally layered site is established in this study. The 3D seismic response of the immersed tunnel in a horizontally layered site subjected to obliquely incident waves is analyzed based on the precise dynamic stiffness matrix of the soil layer and half‐space via combined viscous‐spring boundary and equivalent node stress methods. The nonlinear effects of external and internal site conditions on the whole model were determined by equivalent linearization algorithm and Mohr–Coulomb model, respectively. The proposed model was then applied to investigate the nonlinear seismic response of an immersed tunnel in the Haihe River subjected to seismic waves of oblique incidence. The dislocation (opening) of pipe joints in the immersed tunnel were analyzed to determine the response characteristics of the shear keys and overall displacement of the tunnel; the dynamic responses of the immersed tunnel subjected to obliquely incident seismic waves markedly differ from those of vertically incident seismic SV waves. The maximum stress value of shear keys and the maximum dislocation of the pipe joint appear as upon critical angle. The overall displacement of the tunnel increases as incident angle increases. Under severe earthquake conditions, both the pipe corners and midspan section of the roof and floor are likely to produce crack. These areas need careful consideration in the seismic design of immersed tunnel structures.
Stability Analysis and Chaos Control of Recycling Price Game Model for Manufacturers and Retailers
Authors: Li Ting , Yan Dongyun , Ma Xiaogang
Published: July 2019

With application of nonlinear theory, this paper makes study on the long‐term competition in a recycling price game model by manufacturers and retailers. The paper makes analysis on the local stability of the Nash equilibrium point and gives the corresponding stable region. It has been found that the stability of the whole system would be significantly impacted by the following factors which include adjustment speed of the recycling price, the proportion of recycled products by channels, the sensitivity of consumers for the recycling price, and the price cross‐elasticity between two channels. By means of the simulation technology, the complexity of the recycling price in the system in the long‐term competition has been demonstrated. Owing to the change of parameters, bifurcation, chaos, and other phenomena would appear in the system. When the system is becoming chaotic, the profit of the whole system decreased. All these show that the operational efficiency for the whole system will be impaired by the chaos. Effective chaotic control of the system will be realized by the use of the parameter adaptation method.
Effects of Individualized Treadmill Endurance Training on Oxidative Stress in Skeletal Muscles of Transgenic Sickle Mice
Authors: Gouraud Etienne , Charrin Emmanuelle , Dubé John J. , Ofori-Acquah Solomon F. , Martin Cyril , Skinner Sarah , Chatel Benjamin , Boreau Anaelle , Messonnier Laurent A. , Connes Philippe , Pialoux Vincent , Hautier Christophe , Faes Camille
Published: July 2019

Oxidative stress is a key feature in the pathophysiology of sickle cell disease. Endurance training has been shown to reduce oxidative stress in the heart and the liver of sickle mice. However, the effects of endurance training on skeletal muscles, which are major producers of reactive oxygen species during exercise, are currently unknown. The aim of this study was to evaluate the effect of sickle genotype on prooxidant/antioxidant response to individualized endurance training in skeletal muscles of sickle mice. Healthy and homozygous Townes sickle mice were divided into trained or sedentary groups. Maximal aerobic speed and V̇O2peak were determined using an incremental test on a treadmill. Trained mice ran at 40% to 60% of maximal aerobic speed, 1 h/day, 5 days/week for 8 weeks. Oxidative stress markers, prooxidant/antioxidant response, and citrate synthase enzyme activities were assessed in thegastrocnemius, in theplantaris, and in thesoleusmuscles. Maximal aerobic speed and V̇O2peak were significantly reduced in sickle compared to healthy mice (-57% and -17%;p<0.001). NADPH oxidase, superoxide dismutase, and catalase activities significantly increased after training in thegastrocnemiusof sickle mice only. A similar trend was observed for citrate synthase activity in sickle mice (p=0.06). In this study, we showed an adaptive response to individualized endurance training on the prooxidant/antioxidant balance in thegastrocnemius,but neither in theplantarisnor in thesoleusof trained sickle mice, suggesting an effect of sickle genotype on skeletal muscle response to endurance treadmill training.
Increased Outdoor PM2.5 Concentration Is Associated with Moderate/Severe Anemia in Children Aged 6–59 Months in Lima, Peru
Authors: Morales-Ancajima Valeria C. , Tapia Vilma , Vu Bryan N. , Liu Yang , Alarcón-Yaquetto Dulce E. , Gonzales Gustavo F.
Published: July 2019

Anemia affects 1.62 billion people worldwide. Although iron deficiency is the main cause of anemia, several other factors may explain its high prevalence. In this study, we sought to analyze the association between outdoor particulate matter PM2.5 levels with anemia prevalence in children aged 6–59 months residing in Lima, Peru (n = 139,368), one of the cities with the worst air pollution in Latin America. The study period was from 2012 to 2016. Anemia was defined according to the World Health Organization (Hb < 11 g/dL). PM2.5 values were estimated by a mathematical model that combined data observed from monitors, with satellite and meteorological data. PM2.5 was analyzed by quintiles. Multiple linear and logistic regressions were used to estimate the associations between hemoglobin concentration (beta) and anemia (odds ratio) with PM2.5, after adjusting by covariates. Prevalence of anemia was 39.6% (95% confidence interval (CI): 39.3–39.9). Mild anemia was observed in 30.8% of children and moderate/severe in 8.84% of children. Anemic children compared with nonanemic children are mainly males, have low body weight, higher rate of stunting, and live in an environment with high PM2.5 concentration. A slight decrease in hemoglobin (4Q B: −0.03, 95% CI: −0.05 to −0.02; 5Q B: −0.04, 95% CI: −0.06 to −0.01) and an increase in the probability of moderate/severe anemia (4Q OR: 1.18, 95% CI: 1.10–1.27; 5Q OR: 1.18, 95% CI: 1.08–1.29) were observed with increased exposure to PM2.5. We conclude that outdoor PM2.5 levels were significantly associated with decreased hemoglobin values and an increase in prevalence of moderate/severe anemia in children under 5 years old.
Sodium Oxybate: A Cause of Extreme Involuntary Weight Loss in a Young Lady
Authors: Noujaim Michael G. , Mourad Ahmad , Clough Jeffrey D.
Published: July 2019

We present a case of a young lady with extreme involuntary weight loss and alarming constitutional symptoms found ultimately to be all due to a single medication’s side effects. The objective of this case report is to alert physicians, especially in a primary care setting, that the side effects of a medication used mostly in a highly specialized field of neurology, sodium oxybate (SXB), can cause extreme involuntary weight loss in addition to chronic night sweats and symptoms of clinical depression.
Fault Detection for the Scraper Chain Based on Vibration Analysis Using the Adaptive Optimal Kernel Time‐Frequency Representation
Authors: Zhang Xing , Li Wei , Zhu Zhencai , Yang Shanguo , Jiang Fan
Published: July 2019

A scraper conveyor is a key component of large‐scale mechanized coal mining equipment, and its failure patterns are mainly caused by chain jam and chain fracture. Due to the difficulties with direct measurement for multiple performance parameters of the scraper chain, this paper deals with a novel strategy for fault detection of the scraper chain based on vibration analysis of the chute. First, a chute vibration model (CVM) is applied for modal analysis, and the hammer impact test (HIT) is conducted to validate the accuracy of the CVM; second, the measuring points for vibration analysis of the chute are determined based on the modal assurance criterion (MAC); and third, to simulate the actual vibration properties of the chute, a dynamic transmission system model (DTSM) is constructed based on finite element modeling. The fixed‐point experimental testing (FPET) is then conducted to indicate the correctness of simulation results. Subsequently, the DTSM‐based vibration responses of the chute under different operating conditions are obtained. In this paper, the proposed strategy is employed to determine the occurrence of chain faults by amplitude comparisons, while failure patterns are distinguished by the adaptive optimal kernel time‐frequency representation (AOKR).
The Influence of Additive Manufacturing Processes on the Performance of a Periodic Acoustic Metamaterial
Authors: Kennedy John , Flanagan Lara , Dowling Luke , Bennett G. J. , Rice Henry , Trimble Daniel
Published: July 2019

Advancements in 3D print technology now allow the printing of structured acoustic absorbent materials at the appropriate microscopic scale and sample sizes. The repeatability of the fundamental cell unit of these metamaterials provides a pathway for the development of viable macro models to simulate built-up structures based on detailed models of the individual cell units; however, verification of such models on actual manufactured structures presents a challenge. In this paper, a design concept for an acoustic benchmark metamaterial consisting of an interlinked network of resonant chambers is considered. The form chosen is periodic with cubes incorporating spherical internal cavities connected through cylindrical openings on each face of the cube. This design is amenable to both numerical modelling and manufacture through additive techniques whilst yielding interesting acoustic behaviour. The paper reports on the design, manufacture, modelling, and experimental validation of these benchmark structures. The behaviour of the acoustic metamaterial manufactured through three different polymer-based printing technologies is investigated with reference to the numerical models and a metal powder-based print technology. At the scale of this microstructure, it can be seen that deviations in surface roughness and dimensional fidelity have a comparable impact on the experimentally measured values of the absorption coefficient.
Investigation of Antioxidant and Antimicrobial Activities of Different Extracts of Auricularia and Termitomyces Species of Mushrooms
Authors: Gebreyohannes Gebreselema , Nyerere Andrew , Bii Christine , Sbhatu Desta B.
Published: July 2019

Mushrooms produce a variety of bioactive compounds that are known to have a potential source of antioxidant and antimicrobial properties. Natural antioxidants can protect against free radicals without any side effects. The purpose of this study was to evaluate the antioxidant and antimicrobial activities of Auricularia and Termitomyces extracts. Specimens of Auricularia and Termitomyces spp. were collected from Kakamega National Reserve Forest in Kenya. Specimens were identified, extracted, and screened for their antioxidant and antimicrobial activities using stable free radical DPPH and colorimetric bioassay methods, respectively. The antimicrobial activity of the extracts was tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, MRSA, Candida albicans, and Candida parapsilosis. The maximum scavenging activity of hot water extract of Auricularia spp. was observed at 70.4% with the IC50 value of 40 μg/mL. Of the three extracts of Termitomyces spp., 70% ethanol extract has shown the highest scavenging activity (63%) with the IC50 value of 50 μg/mL. Chloroform and hot water extracts of Auricularia have shown statistically significantly different antifungal activities against C. parapsilosis (df = 2, F = 22.49, p ≤ 0.05). Of all the organisms, S. aureus was highly susceptible to 70% ethanol and hot water extracts of Termitomyces spp. with minimum inhibitory concentration values of 0.67±0.29 mg/mL. S. aureus and E. coli were the most susceptible and resistant bacteria to the hot water extract, respectively. In conclusion, the extracts of Auricularia spp. and Termitomyces spp. have shown promising antimicrobial and antioxidant activities.
CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells
Authors: Wang Fang , Zhao Linlin , Shan Yingguang , Li Ran , Qin Guijun
Published: July 2019

Aims. Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis.Materials and Methods. To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined.Results. Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro.Conclusions. Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.
Carbonate Solvents and Ionic Liquid Mixtures as an Electrolyte to Improve Cell Safety in Sodium-Ion Batteries
Authors: Vo T. D. , Nguyen H. V. , Nguyen Q. D. , Phung Q. , Tran V. M. , Le P. L. M.
Published: July 2019

Ionic liquid-based electrolytes proved to be effective in terms of alleviating the safety problems associated with lithium/sodium ion batteries, especially for large-scale applications, due to their superior thermal stability and nonflammability. The main disadvantage of ionic liquids is their relatively high viscosity. Adding a suitable amount of organic “thinning” solvents could be a potential solution for this problem: while the electrolyte viscosity is greatly reduced, the electrochemical properties and thermal stability remain almost as good as those of pure ionic liquid. In this study, electrolyte mixtures based on 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl) (EMI-TFSI) and carbonate solvents (EC-PC) were prepared. The electrochemical compatibility in half-cell configuration with respect to sodium metal anode of various electrode materials, including SnS/C, hard carbon (HC), and Na0.44MnO2, was evaluated. Moreover, the thermal stability, the flammability, and the conduction mechanism of such electrolyte mixtures were also explored and discussed.
Histological Analysis of Bone Repair in Mandibular Body Osteotomy Using Internal Fixation System in Three Different Gaps without Bone Graft in an Animal Model
Authors: Olate Sergio , Vásquez Bélgica , Sandoval Cristian , Vasconcellos Adriana , Alister Juan Pablo , del Sol Mariano
Published: July 2019

The aim was to analyze histologically the bone repair in a mandibular osteotomy model with different gaps between the segments. Nine male rabbits who underwent osteotomies on the mandibular body were fixed with a 1.5 system plate and no bone graft; group 1 (2 mm gap between segments), group 2 (5 mm gap between segments), and group 3 (8 mm gap between segments) were included. After 8 weeks they were euthanized and the sample was processed for histological analysis. Group 1 showed advanced bone repair with cartilaginous tissue and cancellous bone, showing osteoblasts and type III collagenous fibers. In group 2, a more delayed ossification was observed, with an extensive area of peripheral ossifying cartilage and chondrocytes in greater number at the center of the defect; group 3 showed no evidence of ossification with fibrous tissue, a very low level of chondrocytes, and some bone sequestrate. We can conclude that, in this animal model, 2 or 5 mm gap in the osteotomy could be repaired as bone when fixation is used. The size of the gap is an important factor for the use of bone grafts considering endochondral ossification. This model can be used for graft analysis and related technologies.
Bacillus Cereus Enhanced Phytoremediation Ability of Rice Seedlings under Cadmium Toxicity
Authors: Jan Mehmood , Shah Gulmeena , Masood Sadaf , Iqbal Shinwari Kamran , Hameed Rashida , Rha E. S. , Jamil Muhammad
Published: July 2019

Cadmium (Cd+2) is a highly toxic metal, which significantly alters different biochemical and metabolic processes in plants. Massive amounts of Cd+2 is being released into the environment by different anthropogenic activities. In the present study, plant growth promoting activities of bacterial strain Bacillus cereus was evaluated under Cd+2 stress in two rice cultivars Basmati-385 and Shaheen Basmati. Cd+2 stress significantly decreased plant growth and biomass production in both cultivars. However, with the inoculation of B. cereus under Cd+2 treatments, reduced Cd+2 uptake and increased antioxidant enzymes activities in rice cultivars lead to enhanced plant growth, biomass production, photosynthetic pigments, micronutrients, and lowered electrolytes leakage. This study suggests that B. cereus has the ability to alleviating Cd toxicity and increased phytoremediation efficiency of rice seedling under Cd stress.
Effect of Alginate and Chitosan Edible Coating Enriched with Olive Leaves Extract on the Shelf Life of Sweet Cherries (Prunus avium L.)
Authors: Zam Wissam
Published: July 2019

Edible film coatings are widely used as a protective barrier for the reduction of transpiration and respiration, therefore reducing the ripening process in fruits and vegetables and improving their quality. The influence of chitosan 1% and alginate 3% enriched with olive leaves extract (OLE) on the quality of sweet cherries was studied. Overall, the ripening process and the increase in anthocyanins were found to be delayed with the use of coating particularly those composed of chitosan in combination with OLE. Ascorbic acid and total phenolic contents were recorded with restricted loss at the end of 20 days of storage in both chitosan- and alginate-coated samples enriched with OLE. Higher values of antioxidant activity expressed as the percentage inhibition of DPPH were reported in correlation with phytochemical content. It could be concluded that chitosan and alginate coating enriched with OLE could be efficient for prolonging the shelf life of sweet cherries.
The Third Finger Middle Phalanx Maturation (MPM) Method to Assess Timing of Functional Treatment for Skeletal Class II Malocclusion: Report of Three Cases
Authors: Perinetti Giuseppe
Published: July 2019

A deficient mandibular growth on the sagittal plane is the most frequent diagnostic finding in dentoskeletal Class II malocclusion. Evidence indicated that functional treatment for such malocclusion is efficient only if performed during the pubertal growth spurt, as identified through radiographical growth indicators. With the aim of reducing the radiation to the patients and to follow longitudinally individual growth phases, the use of the sole third finger middle phalanx maturation (MPM), as a 5-stage method, has been proposed. Herein, three clinical cases of skeletal Class II malocclusion in growing patients treated by removable functional appliances (with or without full-fixed appliance treatment) are reported. Timing of intervention was strictly planned according to the MPM method, and skeletal effects have been recorded up to 21 months of follow-up. In all the cases, noteworthy skeletal effects have been achieved in terms of mandibular elongation, with relevant occlusal and aesthetic outcomes. It has also been showed that results are stable or slightly improved after functional treatment. These results would be achieved irrespective of the appliance used and support the use of the MPM method in everyday clinical practice.
Multiobjective Optimization Method for Polymer Injection Molding Based on a Genetic Algorithm
Authors: Yuan Zhijun , Wang Hui , Wei Xuebing , Yan Kui , Gao Cheng
Published: July 2019

To solve the quality problem of polymer injection parts, a quality prediction and multiobjective optimization method is established. In this method, the parameters that have an important effect on the part quality are selected using an orthogonal testing method, and then a central composite design experiment is performed using these parameters. A mathematical model considering an objective and impact factors is developed using the response surface method. The optimal combination of the impact parameters is determined using a multiobjective genetic algorithm. The injection molding of a typical interior trim part of a car, i.e., the seat belt cover plate, is used as an example to demonstrate the method. The two most troublesome problems in this process—the sink marks and warpage—are multiobjectively analyzed using the established method, and the optimal combination of impact parameters that minimized the defects is determined. The errors of the sink marks and warpage between the experimental and theoretical values were 7.95% and 0.2%, respectively. The optimized parameters were tested in actual injection molding. The results show that the shrinkage and warpage of the parts are obviously improved by optimization using the proposed method, allowing the parts to satisfy the requirements of assembly and appearance.
GnRH Antagonists Have Direct Inhibitory Effects On Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 Expression
Authors: Cucchiara Vito , Yang Joy C. , Liu Chengfei , Adomat Hans H. , Tomlinson Guns Emma S. , Gleave Martin E. , Gao Allen C. , Evans Christopher P.
Published: July 2019

Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. Degarelix (Firmagon), a gonadotropin-releasing hormone (GnRH) receptor antagonist differs from luteinizing hormone-releasing hormone (LHRH) agonists by avoiding “testosterone flare” and lower follicle-stimulating hormone (FSH) levels. The direct effect of degarelix and leuprolide on human prostate cancer cells was evaluated. In LNCaP, C4-2BMDVR, and CWR22Rv1 cells, degarelix significantly reduced cell viability compared with the controls (P ≤ 0.01). Leuprolide was stimulatory in the same cell lines. In C4-2B MDVR cells, degarelix alone or combined with abiraterone or enzalutamide reduced the AR-V7 protein expression compared with the control group. SCID mice bearing VCaP xenograft tumors were divided into 4 groups and treated with surgical castration, degarelix, leuprolide, or buffer alone for 4 weeks. Leuprolide slightly suppressed tumor growth compared with the vehicle control group (P > 0.05). Tumors in degarelix-treated mice were 67% of those in the leuprolide-treatment group but 170% larger than in surgically castrated ones. Measurements of intratumoral steroids in serum, tumor samples, or treated cell pellets by LC/MS confirmed that degarelix better decreased the levels of testosterone and steroidogenesis pathway intermediates, comparable to surgical castration, whereas leuprolide had no inhibitory effect. Collectively, our results suggested a selective mechanism of action of degarelix against androgen steroidogenesis and AR-variants. This study provides additional molecular insights regarding the mechanism of degarelix compared with GnRH agonist therapy, which may have clinical implications.
Specific RITA Modification Produces Hyperselective Cytotoxicity While Maintaining In Vivo Antitumor Efficacy
Authors: Peyser Brian D. , Hermone Ann , Salamoun Joseph M. , Burnett James C. , Hollingshead Melinda G. , McGrath Connor F. , Gussio Rick , Wipf Peter
Published: July 2019

The preclinical antitumor agent RITA (2,5-bis[5-hydroxymethyl-2-thienyl] furan, NSC 652287), an analog of the natural product α-terthiophene, failed during the development phase due to acute pulmonary toxicity in animal models. A series of synthetic modifications to RITA's heterocyclic scaffold resulted in activity ranging from broadly cytotoxic to highly selective. In the NCI 60-cell line screen, these “hyperselective” agents (e.g., imatinib) are rare. A selectivity index (SI) was developed to quantify this desirable feature, which is 20 for imatinib, whereas RITA's SI is only 0.10. One of the described hyperselective RITA analogs (SI = 7.9) completely lost activity in the presence of a known SULT1A1 inhibitor. These results, coupled with previous evidence that RITA is a SULT1A1 substrate, suggest that carbinol modification by a sulfate leaving group and subsequent formation of a reactive carbocation may explain RITA's broad cytotoxicity. Although SULT1A1 expression is required for susceptibility, hyperselective analogs exhibited reduced association of activity with SULT1A1 mRNA expression compared with RITA, apparently requiring some additional target(s). In support of this hypothesis, there is a strong correlation (P < 0.01, r = 0.95) between quantum mechanically calculated energy barriers for carbocation formation from sulfonated analogs and SI, indicating that hyperselective RITA analogs generate reactive carbocations less readily after sulfate activation. Importantly, narrowing the cytotoxicity profile of RITA did not eliminate its analogs' in vivo antitumor activity, as several new hyperselective agents, NSC 773097 (1), 773392 (2), and 782846 (6), displayed impressive activity against A498 xenografts in mice.
MicroRNA-203 Acts as a Potent Suppressor in Septic Shock by Alleviating Lung Injury via Inhibition of VNN1
Authors: Ling Lan , Lu Hai-Tao , Wang Hai-Feng , Shen Mei-Jia , Zhang Hong-Bo
Published: July 2019

Background: Septic shock, the most serious complication of sepsis, is a life-threatening disease that is mainly characterized by hypoperfusion and multiple organ failure. Various aberrantly expressed microRNAs (miRNAs) have been reported to be related to septic shock. We explored the regulatory effect of microRNA-203 (miR-203) on lung injury in septic shock mice. Methods: Microarray-based gene expression profiling related to septic shock identified the differentially expressed gene vanin-1 (VNN1) and potential regulatory miR-203. miR-203 was predicted to mediate VNN1 expression, thus affecting septic shock, which was investigated by treatment with miR-203 mimic, miR-203 inhibitor, and siRNA-VNN1 in septic shock mouse models. Polymorphonuclear neutrophils (PMNs) and pulmonary alveolar macrophages in bronchoalveolar lavage fluid (BALF) as well as the wet/dry ratio of the lung were also measured to assess lung injury. Additionally, the effects of miR-203 on inflammatory cytokines, oxidative stress indexes, blood biochemical indexes, serine-threonine protein kinase (AKT) signaling pathway-related factors, and apoptosis-related factors were determined. Results: VNN1 was verified to be targeted and negatively regulated by miR-203. In mouse models of septic shock, weak expression of miR-203, high expression of VNN1, and inhibition of AKT signaling pathway were identified. In response to miR-203 mimic and VNN1 gene silencing, mouse models of septic shock displayed reduced apoptosis, MDA, ALT, and AST in lung tissues, decreased levels of TNF-α, IL-1β, IFN-γ, IL-10, and IL-6, in serum, and reduced PMN and PAM levels in BALF, in addition to elevated SOD activity. Notably, the presence of miR-203 mimic led to AKT signaling pathway activation. Conclusion:This study shows that upregulating miR-203 can alleviate lung injury through activation of the AKT signaling pathway by downregulating VNN1 in septic shock.
Allicin Protects against Cisplatin-Induced Stria Vascularis Damage: Possible Relation to Inhibition of Caspase-3 and PARP-1-AIF-Mediated Apoptotic Pathways
Authors: Cai Jing , Wu Xianmin , Li Xiaofei , Ma Chong , Xu Lei , Guo Xiangrui , Li Jianfeng , Wang Haibo , Han Yuechen
Published: July 2019

Cisplatin is an anti-cancer drug that causes oxotoxic side effects such as impairment of inner ear function and hearing loss. We aimed to investigate the effects of allicin against cisplatin-induced stria vascularis damage in mice, and to clarify the mechanism underlying the protective effects of allicin against ototoxicity. Stria vascularis injury was induced in mice by intraperitoneal injection of cisplatin, which was significantly prevented by pretreatment with allicin. Allicin not only reduced cisplatin-activated expression of cleaved caspase-3 in marginal cells, PVM/Ms (perivascular resident macrophage-like melanocytes), and basal cells of the stria vascularis, but also decreased the expression of poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) nuclear translocation in the stria vascularis cells. Our results demonstrate that allicin plays an effective role in protecting stria vascularis injury induced by cisplatin by inhibiting caspase-dependent, as well as caspase-independent PARP-1-AIF-mediated apoptotic pathways. Therefore, allicin may be useful in preventing cisplatin-induced ototoxicity.
RORA Overexpression Alleviates Nasal Mucosal Injury and Enhances Red Blood Cell Immune Adhesion Function in a Mouse Model of Allergic Rhinitis via Inactivation of the Wnt/β-Catenin Signaling Pathway
Authors: Li Jinqiu , Xue Kai , Zheng Yan , Wang Yinan , Xu Chengbi
Published: July 2019

Background: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). Methods: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/β-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/β-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1β, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, β-catenin, and GSK3β, as well as the extent of β-catenin and GSK-3β phosphorylation were evaluated and measured. Results: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/β-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1β, IL-4, IL-17, β-catenin, and GSK-3β. Moreover, this led to a decreased extent of β-catenin and GSK-3β phosphorylation, while the rates of C3b receptor rosette and Ic rosette were elevated. Conclusion: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/β-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.
Brain Structure and Subclinical Symptoms: A Dimensional Perspective of Psychopathology in the Depression and Anxiety Spectrum
Authors: Besteher Bianca , Gaser Christian , Nenadić Igor
Published: July 2019

Human psychopathology is the result of complex and subtle neurobiological alterations. Categorial DSM or ICD diagnoses do not allow a biologically founded and differentiated description of these diverse processes across a spectrum or continuum, emphasising the need for a scientific and clinical paradigm shift towards a dimensional psychiatric nosology. The subclinical part of the spectrum is, however, of special interest for early detection of mental disorders. We review the current evidence of brain structural correlates (grey matter volume, cortical thickness, and gyrification) in non-clinical (psychiatrically healthy) subjects with minor depressive and anxiety symptoms. We identified 16 studies in the depressive spectrum and 20 studies in the anxiety spectrum. These studies show effects associated with subclinical symptoms in the hippocampus, anterior cingulate cortex, and anterior insula similar to major depression and changes in amygdala similar to anxiety disorders. Precuneus and temporal areas as parts of the default mode network were affected specifically in the subclinical studies. We derive several methodical considerations crucial to investigations of brain structural correlates of minor psycho(patho)logical symptoms in healthy participants. And we discuss neurobiological overlaps with findings in patients as well as distinct findings, e.g. in areas involved in the default mode network. These results might lead to more insight into the early pathogenesis of clinical significant depression or anxiety and need to be enhanced by multi-centre and longitudinal studies.
Cultural adaptation of the Retirement Resources Inventory for Brazilian culture
Authors: Gvozd Raquel , Rossaneis Mariana Angela , Pissinati Paloma De Souza Cavalcante , Guirardello Edinêis De Brito , Haddad Maria do Carmo Fernandez Lourenço
Published: July 2019

OBJECTIVE: To translate and adapt the Retirement Resources Inventory for Brazilian culture. METHODS: Methodological research including the stages of translation, synthesis, evaluation by committee of judges, back-translation and pre-test. The internal consistency of the instrument with Cronbach’s alpha coefficient was evaluated. RESULTS: We considered the stages of translation and cultural adaptation adequate. The evaluation of the synthesis version by the judges resulted in the need to change 95.0% of the items to ensure the semantic, idiomatic, cultural and conceptual equivalence between the original and translated versions. In general consensus of the instrument, the agreement rate among the judges for the equivalences was 84.4%. As for the pre-test stage, 25 pre-retirees participated. The participants suggested adjustments in the instrument. The instrument’s internal consistency was 0.85. The mean time to fill in the instrument was 18.7 minutes. CONCLUSIONS: The methodological process of cultural adaptation of the Retirement Resources Inventory resulted in adequate content validity and ease of understanding by the participants. We emphasize that this study precedes the evaluation process of the psychometric properties of the instrument, which will be carried out in new studies.