bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixation target representation in prefrontal cortex during the antisaccade task
Authors: Zhou Xin , Constantinidis Christos
Published: February 2017

Neurons that discharge strongly during the time period of fixation of a visual target and cease to discharge before saccade initiation have been described in the brain stem, superior colliculus, and cortical areas. In subcortical structures, fixation neurons play a reciprocal role with saccadic neurons during the generation of eye movements. Their role in the dorsolateral prefrontal cortex is less obvious, and it is not known if they are activated by fixation, inhibit saccade generation, or play a role in more complex functions such as the inhibition of inappropriate responses. We examined the properties of prefrontal fixation neurons in the context of an antisaccade task, which requires an eye movement directed away from a prepotent visual stimulus. We tested monkeys with variants of the task, allowing us to dissociate activity synchronized on the fixation offset, presentation of the visual stimulus, and saccadic onset. Fixation neuron activity latency was most strongly tied to the offset of the fixation point across task variants. It was not well predicted by the appearance of the visual stimulus, which is essential for planning of the correct eye movement and inhibiting inappropriate ones. Activity of fixation neurons was generally negatively correlated with that of saccade neurons; however, critical differences in timing make it unlikely that they provide precisely timed signals for the generation of eye movements. These results demonstrate the role of fixation neurons in the prefrontal cortex during tasks requiring timing of appropriate eye movement and inhibition of inappropriate actions.

NEW & NOTEWORTHY Properties of neurons that discharge during eye fixation and go silent before saccade initiation have been described in subcortical structures involved in eye movement generation, but their role in the dorsolateral prefrontal cortex presents a puzzle. Our results demonstrate the role of fixation neurons in the prefrontal cortex during tasks requiring precise timing of appropriate eye movement and inhibition of inappropriate actions.
New Class of Antimicrobial Agents: SBA-15 Silica Containing Anchored Copper Ions
Authors: Laskowski Lukasz , Laskowska Magdalena , Fijalkowski Krzysztof , Piech Henryk , Jelonkiewicz Jerzy , Jaskulak Marta , Gnatowski Adam , Dulski Mateusz
Published: February 2017

The paper is about a new class of antimicrobial functional nanomaterials. Proposed compounds are based on SBA-15 porous silica matrices and contain anchored copper ions. Thanks to the immobilization of functional groups the compounds are safer for environment than commonly used disinfectant agents. We prepared and examined silica based materials containing two concentrations of copper-containing groups: 10 and 5%. For the reference we prepared samples containing free-standing CuO molecules in the structure and checked their antimicrobial properties. Antibacterial effect of considered SBA-15-Cu material was tested onEscherichia colibacteria. Antimicrobial tests were applied for the pure form of the material and as modifying agents for plastics. The obtained results showed that the sample with lower concentration of active copper-containing groups has stronger antimicrobial properties than the one with higher concentration of copper. Interestingly, silica containing free-standing CuO molecules has no antimicrobial properties. Considering the obtained results, we can conclude that the most probable antimicrobial mechanism in this case is an oxidation stress. When a plastic modifier is applied the material is enriched with bacterial inhibitory properties. It seems that SBA-15 silica containing low concentration of anchored copper ions is promising in terms of its antibacterial property and biomaterial potential for commercial use.
Hyperphosphatemia and hs-CRP Initiate the Coronary Artery Calcification in Peritoneal Dialysis Patients
Authors: Shang Da , Xie Qionghong , Shang Bin , Zhang Min , You Li , Hao Chuan-Ming , Zhu Tongying
Published: February 2017

Background.Coronary artery calcification (CAC) contributes to high risk of cardiocerebrovascular diseases in dialysis patients. However, the risk factors for CAC initiation in peritoneal dialysis (PD) patients are not known clearly.Methods.Adult patients with baseline CaCS = 0 and who were followed up for at least 3 years or until the conversion from absent to any measurable CAC detected were included in this observational cohort study. Binary logistic regression was performed to identify the risk factors for CAC initiation in PD patients.Results.70 patients recruited to our study were split into a noninitiation group (n=37) and an initiation group (n=33) according to the conversion of any measurable CAC during their follow-up or not. In univariate analysis, systolic blood pressure, serum phosphorus, fibrinogen, hs-CRP, serum creatinine, and triglycerides were positively associated with the initiation of CAC, while the high density lipoprotein and nPCR did the opposite function. Multivariate analysis revealed that hyperphosphatemia and hs-CRP were the independent risk factors for CAC initiation after adjustments.Conclusions.Hyperphosphatemia and hs-CRP were the independent risk factors for CAC initiation in PD patients. These results suggested potential clinical strategies to prevent the initiation of CAC in PD patients.
Biochemical and Clinical Assessments of Segmental Maxillary Posterior Tooth Intrusion
Authors: Tasanapanont Jintana , Wattanachai Tanapan , Apisariyakul Janya , Pothacharoen Peraphan , Ongchai Siriwan , Kongtawelert Prachya , Midtbø Marit , Jotikasthira Dhirawat
Published: February 2017

Objective. To compare chondroitin sulphate (CS) levels around maxillary second premolars, first molars, and second molars between the unloaded and the loaded periods and to measure the rates of intrusion of maxillary posterior teeth during segmental posterior tooth intrusion. Materials and Methods. In this prospective clinical study, 105 teeth (from 15 patients exhibiting anterior open bite and requiring maxillary posterior tooth intrusion) were studied. Competitive ELISA was used to detect CS levels. Dental casts (during the unloaded and loaded periods) were scanned, and posterior tooth intrusion distances were measured. Results. During the unloaded period, the median CS levels around maxillary second premolars, first molars, second molars (experimental teeth), and mandibular first molars (negative control) were 0.006, 0.055, 0.056, and 0.012 and during the loaded period were 2.592, 5.738, 4.727, and 0.163 ng/μg of total protein, respectively. The median CS levels around experimental teeth were significantly elevated during the loaded period. The mean rates of maxillary second premolar and first and second molar intrusion were 0.72, 0.58, and 0.40 mm/12 weeks, respectively. Conclusions. Biochemical and clinical assessments suggested that the segmental posterior tooth intrusion treatment modality with 50 g of vertical force per side was sufficient. Trial Registration. The study is registered as TCTR20170206006.
PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells
Authors: He Jia , Long Chongde , Huang Zixin , Zhou Xin , Kuang Xielan , Liu Lanying , Liu Huijun , Tang Yan , Fan Yuting , Ning Jie , Ma Xinqi , Zhang Qingjiong , Shen Huangxuan
Published: February 2017

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α(one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.
Pituitary Adenoma and Hyperprolactinemia Accompanied by Idiopathic Granulomatous Mastitis
Authors: Destek Sebahattin , Gul Vahit Onur , Ahioglu Serkan , Serin Kursat Rahmi
Published: February 2017

Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of the breast, and its etiology remains not fully elucidated. IGM is observed more often in patients with autoimmune disease. Hyperprolactinemia is observed during pregnancy, lactation, and a history of oral contraceptive use. A 39-year-old patient with no history of oral contraceptive use presented with complaints such as redness, pain, and swelling in her left breast. Ultrasound and magnetic resonance imaging (MRI) revealed a suspicious inflamed mass lesion. Core biopsy was performed to exclude breast cancer and to further diagnose. The breast abscess was drained and steroids were given for treatment. In order to monitor any progression during the three months of treatment, hormone levels were routinely examined. Prolactin level was above the reference range, and pituitary MRI revealed a pituitary prolactinoma. After treatment with prolactin inhibitors, IGM also improved with hyperprolactinemia. This report emphasizes attention to hyperprolactinemia in cases of IGM diagnosis and treatment.
Resource Allocation Optimization Model of Collaborative Logistics Network Based on Bilevel Programming
Authors: Xu Xiao-feng , Chang Wei-hong , Liu Jing
Published: February 2017

Collaborative logistics network resource allocation can effectively meet the needs of customers. It can realize the overall benefit maximization of the logistics network and ensure that collaborative logistics network runs orderly at the time of creating value. Therefore, this article is based on the relationship of collaborative logistics network supplier, the transit warehouse, and sellers, and we consider the uncertainty of time to establish a bilevel programming model with random constraints and propose a genetic simulated annealing hybrid intelligent algorithm to solve it. Numerical example shows that the method has stronger robustness and convergence; it can achieve collaborative logistics network resource allocation rationalization and optimization.
The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies
Authors: Stellaard Frans , Lütjohann Dieter
Published: February 2017

The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated byde novosynthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepaticde novosynthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker ofde novocholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepaticde novosynthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepaticde novosynthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.
Chloride-Induced Corrosion of Steel in Concrete: An Overview on Chloride Diffusion and Prediction of Corrosion Initiation Time
Authors: Khan Muhammad Umar , Ahmad Shamsad , Al-Gahtani Husain Jubran
Published: February 2017

Initiation of corrosion of steel in reinforced concrete (RC) structures subjected to chloride exposures mainly depends on coefficient of chloride diffusion, Dc, of concrete. Therefore, Dc is one of the key parameters needed for prediction of initiation of reinforcement corrosion. Fick’s second law of diffusion has been used for long time to derive the models for chloride diffusion in concrete. However, such models do not include the effects of various significant factors such as chloride binding by the cement, multidirectional ingress of chloride, and variation of Dc with time due to change in the microstructure of concrete during early period of cement hydration. In this paper, a review is presented on the development of chloride diffusion models by incorporating the effects of the key factors into basic Fick’s second law of diffusion. Determination of corrosion initiation time using chloride diffusion models is also explained. The information presented in this paper would be useful for accurate prediction of corrosion initiation time of RC structures subjected to chloride exposure, considering the effects of chloride binding, effect of time and space on Dc, and interaction effect of multidirectional chloride ingress.
Interleukin 35 Polymorphisms Are Associated with Decreased Risk of Premature Coronary Artery Disease, Metabolic Parameters, and IL-35 Levels: The Genetics of Atherosclerotic Disease (GEA) Study
Authors: Posadas-Sánchez Rosalinda , Pérez-Hernández Nonanzit , Angeles-Martínez Javier , López-Bautista Fabiola , Villarreal-Molina Teresa , Rodríguez-Pérez José Manuel , Fragoso José Manuel , Posadas-Romero Carlos , Vargas-Alarcón Gilberto
Published: February 2017

Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms ofIL-12AandEBI3genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. TheIL-12AandEBI3polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, theEBI3rs428253 (OR = 0.831,Padd= 0.036; OR = 0.614,Prec= 0.033; OR = 0.591,Pcod2= 0.027) andIL-12Ars2243115 (OR = 0.674,Padd= 0.010; OR = 0.676,Pdom= 0.014; OR = 0.698,Phet= 0.027; OR = 0.694,Pcod1= 0.024) polymorphisms were associated with decreased risk of developing premature CAD. Some polymorphisms were associated with clinical and metabolic parameters. Significant different levels of IL-35 were observed inEBI3rs4740 and rs4905 genotypes only in the group of healthy controls. In summary, our study suggests that theEBI3andIL-12Apolymorphisms play an important role in decreasing the risk of developing premature CAD; it also demonstrates the relationship of theEBI3rs4740 and rs4905 genotypes with IL-35 levels in healthy individuals.
The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock
Authors: Chen Xiaoli , Wang Ning , Zhu Yuanfeng , Lu Yongling , Liu Xin , Zheng Jiang
Published: February 2017

Activation of the NLRP3 inflammasome, which catalyzes maturation of proinflammatory cytokines like IL-1βand IL-18, is implicated and essentially involved in many kinds of inflammatory disorders. Chloroquine (CQ) is a traditional antimalarial drug and also possesses an anti-inflammatory property. In this study, we investigated whether CQ suppresses NLRP3 inflammasome activation and thereby confers protection against murine endotoxic shock. CQ attenuated NF-κB and MAPK activation and prohibited expression of IL-1β, IL-18, andNlrp3in LPS treated murine bone marrow-derived macrophages (BMDMs), demonstrating its inhibitory effect on the priming signal of NLRP3 activation. Then, CQ was shown to inhibit caspase-1 activation and ASC specks formation in BMDMs, which indicates that CQ also suppresses inflammasome assembly, the second signal for NLRP3 inflammasome activation. In a murine endotoxic shock model, CQ effectively improved survival and markedly reduced IL-1βand IL-18 production in serum, peritoneal fluid, and lung tissues. Moreover, CQ reduced protein levels of NLRP3 and caspases-1 p10 in lung homogenates of mice with endotoxic shock, which may possibly explain its anti-inflammatory activity and life protection efficacy in vivo. Overall, our results demonstrate a new role of CQ that facilitates negative regulation on NLRP3 inflammasome, which thereby confers protection against lethal endotoxic shock.
A Novel Low-Cost Real-Time Power Measurement Platform for LoWPAN IoT Devices
Authors: Liu Yang , Wang Yubing , Gao Weiwei , Zhang Wuxiong , Qian Hua , Yang Yang
Published: February 2017

With the rapid development of technology and application for Internet of Things (IoT), Low-Power Wireless Personal Area Network (LoWPAN) devices are more popularly applied. Evaluation of power efficiency is important to LoWPAN applications. Conventional method to evaluate the power efficiency of different LoWPAN devices is as follows: first measure the current of the devices under working/idle/sleep state and then make an average and estimation of the lifetime of batteries, which deeply relied on the accuracy of testing equipment and is not that accurate and with high cost. In this work, a low-cost, real-time power measurement platform called PTone is proposed, which can be used to detect the real-time power of LoWPAN devices (above 99.63%) and be able to determine the state of each module of DUT system. Based on the PTone, a novel abnormal status diagnosis mechanism is proposed. The mechanism can not only judge abnormal status but also find accurate abnormal status locating and classify abnormal status accurately. According to the method, each state of Device Under Test (DUT) during wireless transmission is estimated, different abnormal status can be classified, and thus specific location of abnormal module can be found, which will significantly shorten the development process for LoWPAN devices and thus reduce costs.
HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer
Authors: Court Karem A. , Hatakeyama Hiroto , Wu Sherry Y. , Lingegowda Mangala S. , Rodríguez-Aguayo Cristian , López-Berestein Gabriel , Ju-Seog Lee , Rinaldi Carlos , Juan Eduardo J. , Sood Anil K. , Torres-Lugo Madeline
Published: February 2017

Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966–76. ©2017 AACR.
Bariatric Surgery: A Novel Risk Factor for Food Allergy?
Authors: Blockhuys Magali , Faber Margaretha A. , Sabato Vito , Hubens Guy , Ebo Didier G.
Published: February 2017

In this case report, we describe a birch pollen-allergic patient in whom a Fobi pouch gastric bypass was associated with the transition from a mild, localized, birch pollen-related oral allergy syndrome to more severe, generalized allergic reactions to peach.
Clinical Evidence of Increase in Hair Growth and Decrease in Hair Loss without Adverse Reactions Promoted by the Commercial Lotion ECOHAIR®
Authors: Alonso María Rosario , Anesini Claudia
Published: February 2017

Background/Aims: Hair exerts protection, sensory functions, thermoregulation, and sexual attractiveness. Hair loss (alopecia) is caused by several diseases, drug intake, hormone imbalance, stress, and infections (Malassesia furfur). Drugs usually used in alopecia produce irreversible systemic and local side effects. An association of extracts of Coffea arabica and Larrea divaricata (ECOHAIR®) is successfully being commercialized in Argentina for hair growth. The aim of this study was to provide scientific support for the efficacy and innocuousness of ECOHAIR® in patients with noncicatricial alopecia during a 3-month treatment. Methods: The efficacy was determined through the assessment of an increase in hair volume, improvement in hair looks, growth of new hair, and a decrease in hair loss by the test of hair count and hair traction. The capacity to decrease the amount of dandruff was also evaluated as well as the adverse local effects caused by the treatment. Results: ECOHAIR® spray improved the overall hair volume and appearance; it increased its thickness, induced hair growth, and decreased hair loss. Besides, no adverse local reactions were observed upon treatment with the product. Conclusion: This study provides scientific support for the clinical use of ECOHAIR® as a treatment to be used in noncicatricial alopecia.
Risk of Cancer in Patients with Autoimmune Pancreatitis: A Single-Center Experience from Germany
Authors: Schneider Alexander , Hirth Michael , Münch Markus , Weiss Christel , Löhr J. Matthias , Ebert Matthias P. , Pfützer Roland H.
Published: February 2017

Background/Aims: Autoimmune pancreatitis (AIP) has been associated with an increased risk of malignant diseases. We aimed to describe the incidence of malignant diseases in patients with AIP compared to the general population and to characterize the clinical presentation of these patients. Methods: We retrospectively analyzed data from 28 patients with AIP presenting to the clinic (periods 1998 until 2010, 2012 until September 2015). We retrieved the expected cancer incidence of the general population from the German cancer registry. We determined the ratio of patients with malignant disease, characterized the clinical presentation of these patients, and calculated standardized incidence ratios (SIR). Results: We observed 6 malignant diseases in 5 patients with AIP (non-Hodgkin lymphoma, colon cancer, breast cancer and ovarian carcinoma, breast cancer, bladder cancer, n = 5/28, 17.9%) during an overall observation period of 223 person-years (2,675 months). The overall SIR of cancer in patients with AIP was 17.3 (95% CI 5.9-35.8), and the overall incidence rate of malignant diseases in these patients was significantly increased compared to the expected incidence in the German population (Fisher's exact test, p < 0.001). Conclusion: The incidence of malignant diseases in patients with AIP is significantly increased compared to the general population. Careful clinical monitoring is required in individuals with AIP to exclude the occurrence of malignancy.
Oral and Sublingual Immunotherapy: Potential Causes for Eosinophilic Gastrointestinal Disorders?
Authors: Babaie Delara , Mesdaghi Mehrnaz , Nishino Makoto , Mansouri Mahboubeh , Ebisawa Motohiro
Published: February 2017

Food allergy is a common health problem worldwide, with increasing prevalence during recent decades. The only approved treatments for food allergy are food avoidance and administration of emergency medications in case of accidental exposure, which negatively affects patients' quality of life, so new treatments are highly desirable. Different food immunotherapy modalities have recently been used, with variable success rates in the induction of desensitization and tolerance, and different numbers and types of adverse reactions. Adverse reactions, especially intolerable gastrointestinal symptoms, are the most important causes of immunotherapy withdrawal. Eosinophilic esophagitis has been reported as a complication of milk, egg, and peanut oral immunotherapies and sublingual immunotherapy for respiratory allergies, but not for food allergies. Eosinophilic gastritis and eosinophilic colitis also rarely happened following egg and milk oral immunotherapies. The patients undergoing oral and sublingual immunotherapies should be closely followed up for a long time, and those with gastrointestinal symptoms should be evaluated by endoscopy of the gastrointestinal tract. These complications are usually reversible after early diagnosis and stopping the immunotherapy protocol.
Lung Ultrasound in Hemodialysis: A Card to be Played?
Authors: Di Nicolò Pierpaolo , Magnoni Giacomo , Granata Antonio
Published: February 2017

The end-stage renal disease is characterized by a profound impairment in the regulation of body fluid distribution, and volume assessment in hemodialysis is one of the challenging goals for the nephrologist. To determine a state of euvolemia, different validated techniques have been employed and among them lung ultrasonography (LUS) has recently attracted growing attention on account of its capacity to estimate accurately extra vascular lung water and to detect lung edema even in its early asymptomatic stage, that is, hidden lung congestion.With its noninvasiveness, freedom from radiation, the ease of use, acceptable intra/inter-operator reproducibility and availability of portable ultrasound devices, LUS can be considered one of the most interesting “cards to play” for the volume assessment in patients on hemodialysis.
The Novel Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) Alone and in Dual-Targeting Approaches Demonstrates Antitumoral Efficacy in Neuroendocrine Tumors in vitro
Authors: Aristizabal Prada Elke Tatjana , Nölting Svenja , Spoettl Gerald , Maurer Julian , Auernhammer Christoph Josef
Published: February 2017

Background/Aim: Cyclin-dependent kinases (CDKs) are crucial for cell cycle regulation, and alterations in the cell cycle are often observed in human cancer. CDK4/6 in particular orchestrates G1 phase progression and the G1/S transition. Here, we investigated the in vitro effects of the CDK4/6 inhibitor LEE011 in human neuroendocrine tumor cells. Methods: The human neuroendocrine tumor cell lines BON1, QGP1, NCI-H727 and GOT1 were treated with different concentrations of LEE011 alone and in combination with 5-fluorouracil and everolimus. Results: Cell viability decreased in a time- and dose-dependent manner in BON1, QGP1, and NCI-H727 cells upon LEE011 treatment, whereas GOT1 cells were treatment resistant. Treatment sensitivity towards LEE011 was associated with the high expression of cyclin D1 and Rb. LEE011 caused the dephosphorylation of Rb and a subsequent G1 phase cell cycle arrest. Combined treatment with LEE011 and 5-fluorouracil or everolimus showed a significant enhancement in the inhibition of cell viability when compared to single-substance treatments due to PI3K-Akt-mTOR and Ras-Raf-MEK-ERK pathway downregulation and cooperative downregulation of cell cycle components. However, LEE011 also exhibited antagonizing effects with 5-fluorouracil, protecting NET cells from DNA-damaging chemotherapy by blocking PARP cleavage and caspase-3/7 activity. Conclusions: Our data demonstrate that the CDK 4/6 inhibitor LEE011 exhibits promising anti-tumoral properties alone and in combination treatment approaches with 5-fluorouracil or everolimus in human neuroendocrine tumor cell lines.
Chronic Administration of Rosa canina Hydro-Alcoholic Extract Attenuates Depressive-Like Behavior and Recognition Memory Impairment in Diabetic Mice: A Possible Role of Oxidative Stress
Authors: Farajpour Ramin , Sadigh-Eteghad Saeed , Ahmadian Nahid , Farzipour Mohammad , Mahmoudi Javad , Majdi Alireza
Published: February 2017

Objective: This study was designed to evaluate whether chronic Rosa canina (RC) extract administration could improve recognition memory and depressive-like behavior in diabetic mice. Materials and Methods: Seventy-five male albino mice (25-30 g) were randomly divided into 5 groups (15 in each group). A single intraperitoneal injection of 200 mg/kg streptozotocin (STZ) was administered to the mice to induce diabetes. The control group received normal saline, and the diabetic groups received normal saline or 50, 250, and 500 mg/kg of RC extract for 28 days. The mice were weighed each week. Recognition memory and depressive-like behavior were assessed using forced swimming and novel object recognition (NOR) tests, respectively. Malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured in the mouse brain homogenate to evaluate oxidative stress. Statistical analysis was conducted using SPSS, version 22. Results: The groups receiving 250 or 500 mg/kg RC had significantly lower immobility time (159.4 ± 4.7 and 150.1 ± 3.1 s) compared to the sham control group (192.1 ± 7.8 s) in the forced swimming test, and a higher discrimination index (0.39 ± 0.02 and 0.48 ± 0.03) was seen in diabetic animals in the NOR task compared to the sham control group (0.2 ± 0.01). Also, the groups receiving treatment with RC (250 and 500 mg/kg) had significantly higher TAC (0.92 ± 0.04 and 0.96 ± 0.05 mmol/L) and lower MDA (0.76 ± 0.02 and 0.67 ± 0.03 nmol/mg protein) levels in the brains in comparison to the model group. In the 3rd and 4th weeks of study, the RC-treated mice (250 and 500 mg/kg) gained more weight (31.2 ± 0.3 and 32.4 ± 0.3 g, and 31.3 ± 0.2 and 33.7 ± 0.3 g, respectively) than the diabetic group (30 ± 0.2 and 29.6 ± 0.3 g). Conclusion: This study showed that RC attenuated impairment of recognition memory and depressive-like behavior probably through modulation of oxidative stress in an STZ model of diabetes in mouse brains.
Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca
2+
Regulation
Authors: Shanks Julia , Herring Neil , Johnson Errin , Liu Kun , Li Dan , Paterson David J.
Published: February 2017

Reduced cardiomyocyte excitation–contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague–Dawley, Wistar Kyoto, and spontaneously hypertensive rats. Neurons were infected with Ad-mCherry or Ad-mCherry-hATP2Aa (SERCA2a). Intracellular Ca
2+
changes were measured using fura-2AM in response to KCl, caffeine, thapsigargin, and carbonylcyanide-
p
-trifluoromethoxyphenylhydrazine to mobilize intracellular Ca
2+
stores. The effect of SERCA2a on neurotransmitter release was measured using [
3
H]-norepinephrine overflow from 340 to 360 g Sprague–Dawley rat atria in response to right stellate ganglia stimulation. Upregulation of SERCA2a resulted in greater neurotransmitter release in response to stellate stimulation compared with control (empty: 98.7±20.5 cpm, n=7; SERCA: 186.5±28.41 cpm, n=8;
P
<0.05). In isolated Sprague–Dawley rat stellate neurons, SERCA2a overexpression facilitated greater depolarization-induced Ca
2+
transients (empty: 0.64±0.03 au, n=57; SERCA: 0.75±0.03 au, n=68;
P
<0.05), along with increased endoplasmic reticulum and mitochondria Ca
2+
load. Similar results were observed in Wistar Kyoto and age-matched spontaneously hypertensive rats, despite no further increase in endoplasmic reticulum load being observed in the spontaneously hypertensive rat (spontaneously hypertensive rats: empty, 0.16±0.04 au, n=18; SERCA: 0.17±0.02 au, n=25). In conclusion, SERCA2a upregulation in cardiac sympathetic neurons resulted in increased neurotransmission and increased Ca
2+
loading into intracellular stores. Whether the increased Ca
2+
transient and neurotransmission after SERCA2A overexpression contributes to enhanced sympathoexcitation in heart failure patients remains to be determined.
Adiposity and Blood Pressure in 110 000 Mexican Adults
Authors: Gnatiuc Louisa , Alegre-Díaz Jesus , Halsey Jim , Herrington William G. , López-Cervantes Malaquías , Lewington Sarah , Collins Rory , Tapia-Conyer Roberto , Peto Richard , Emberson Jonathan R. , Kuri-Morales Pablo
Published: February 2017

Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111 911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35 to 89 years, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic and diastolic blood pressure of 2 markers of general adiposity (body mass index and height-adjusted weight) and 4 markers of central adiposity (waist circumference, hip circumference, waist:hip ratio, and waist:height ratio), adjusted for relevant confounders. Mean (SD) adiposity levels were: body mass index (28.7±4.5 kg/m
2
), height-adjusted weight (70.2±11.2 kg), waist circumference (93.3±10.6 cm), hip circumference (104.0±9.0 cm), waist:hip ratio (0.90±0.06), and waist:height ratio (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 SD higher measured adiposity marker was associated with a 3 mm Hg higher systolic blood pressure and 2 mm Hg higher diastolic blood pressure (SEs <0.1 mm Hg), but for the waist:hip ratio, associations were only approximately half as strong. General adiposity associations were independent of central adiposity, but central adiposity associations were substantially reduced by adjustment for general adiposity. Findings were similar for men and women. In Mexican adults, often overweight or obese, markers of general adiposity were stronger independent predictors of blood pressure than measured markers of central adiposity, with no threshold effects.
High Ambulatory Arterial Stiffness Index Is an Independent Risk Factor for Rapid Age-Related Glomerular Filtration Rate Decline in the General Middle-Aged Population
Authors: Eriksen Bjørn Odvar , Stefansson Vidar Tor Nyborg , Jenssen Trond Geir , Mathisen Ulla Dorte , Schei Jørgen , Solbu Marit Dahl , Wilsgaard Tom , Melsom Toralf
Published: February 2017

Arterial stiffness is a risk factor for cardiovascular and chronic kidney disease. However, the role of arterial stiffness as a predictor of the age-related glomerular filtration rate (GFR) decline in the general population remains unresolved because of difficulty in measuring GFR with sufficient precision in epidemiological studies. The ambulatory arterial stiffness index (AASI) is a proposed indicator of arterial stiffness easily calculated from ambulatory blood pressure. We investigated whether AASI could predict GFR decline measured as iohexol clearance in the general population. We calculated AASI from baseline ambulatory blood pressure and measured the iohexol clearance at baseline and follow-up in the RENIS-FU study (Renal Iohexol Clearance Survey Follow-Up). AASI was defined as 1 minus the regression slope of the diastolic blood pressure measurement over the systolic blood pressure measurement for each patient. The RENIS cohort included a representative sample of the general middle-aged population without baseline diabetes mellitus, cardiovascular disease, or kidney disease (n=1608). The participant age was 50 to 62 years old at baseline, and the median observation time was 5.6 years. The mean (SD) of the GFR decline rate was 0.95 mL/min per year (2.23) and that of the AASI was 0.38 mL/min per year (0.13). Baseline ambulatory blood pressure or the night/day systolic or diastolic ambulatory blood pressure ratios were not associated with GFR decline. In multivariable-adjusted linear mixed regression analysis, 1 SD of increase in the baseline AASI was associated with a 0.14 mL/min per year (95% confidence interval, −0.26 to −0.02) steeper GFR decline. We conclude that the AASI is an independent risk factor for accelerated age-related GFR decline in the general middle-aged population.
Long‐Term Administration of Eicosapentaenoic Acid Improves Post–Myocardial Infarction Cardiac Remodeling in Mice by Regulating Macrophage Polarization
Authors: Takamura Masayuki , Kurokawa Keisuke , Ootsuji Hiroshi , Inoue Oto , Okada Hikari , Nomura Ayano , Kaneko Shuichi , Usui Soichiro
Published: February 2017

Background

Consumption of n‐3 fatty acids reduces the incidence of cardiovascular mortality in populations that consume diets rich in fish oil. Eicosapentaenoic acid (
EPA
) is an n‐3 fatty acid known to reduce the frequency of nonfatal coronary events; however, the frequency of mortality after myocardial infarction (
MI
) is not reduced. The aims of this study were to determine whether long‐term administration of
EPA
regulated cardiac remodeling after
MI
and to elucidate the underlying therapeutic mechanisms of
EPA
.

Methods and Results

C57
BL
/6J mice were divided into control (phosphate‐buffered saline–treated) and
EPA
‐treated groups. After 28 days of treatment, the mice were subjected to either sham surgery or
MI
by left anterior descending coronary artery ligation. Mortality due to
MI
or heart failure was significantly lower in the
EPA
‐treated mice than in the phosphate‐buffered saline–treated mice. However, the incidence of cardiac rupture was comparable between the
EPA
‐treated mice and the phosphate‐buffered saline–treated mice after
MI
. Echocardiographic tests indicated that
EPA
treatment attenuated post‐
MI
cardiac remodeling by preventing issues such as left ventricular systolic dysfunction and left ventricle dilatation 28 days after
MI
induction. Moreover, during the chronic remodeling phase, ie, 28 days after
MI
, flow cytometry demonstrated that
EPA
treatment significantly inhibited polarization toward proinflammatory M1 macrophages, but not anti‐inflammatory M2 macrophages, in the infarcted heart. Furthermore,
EPA
treatment attenuated fibrosis in the noninfarcted remote areas during the chronic phase.

Conclusions

Long‐term administration of
EPA
improved the prognosis of and attenuated chronic cardiac remodeling after
MI
by modulating the activation of proinflammatory M1 macrophages.
The Voluntary Nature of the Nehemiah Covenant in Rabbinic Literature
Authors: Glatt-Gilad David A.
Published: February 2017

Much scholarly attention has been devoted to the central covenant text in Nehemiah, namely, chapters 8–10, in terms of its sources, literary structure, and theology. An important aspect of the discussion is the consensual spirit with which the Nehemiah covenant was undertaken, even more so than the Sinai covenant, which is referenced in the Nehemiah material (Neh. 9:13). Rabbinic sources, from the Jerusalem Talmud through the various midrashic collections, also put a marked emphasis on the spirit of voluntarism and religious initiative that characterizes the post-exilic covenant experience. Thus the rabbinic sources anticipate certain conclusions of modern scholarship, at least on the ideational level. This paper suggests that the rabbis’ attraction to the theme of voluntary acceptance of the covenant stipulations on the part of the post-exilic community stems from the view of that theme as a conceptual forerunner for the popular acceptance of rabbinic authority.
The Rise and Fall of Jewish Philological Exegesis on the Bible in the Middle Ages: Causes and Effects
Authors: Viezel Eran
Published: February 2017

In the course of the ninth century ce Jewish intellectuals in the Babylonian cultural sphere began to interpret the Bible literally, on the basis of language, syntax, and context. This hermeneutic method, called peshat exegesis spread from the East to the West and reached its apex in the twelfth century in northern France. However, the peshat method of interpretation flourished for a short time only and then declined, first in lands under the rule of Islam and afterwards also in Christian Europe. The question of the causes that led to the development of this hermeneutical method, its waxing and its waning, is one of the most basic questions in the study of medieval biblical exegesis. Nonetheless, no study devoted to a comprehensive explanation of the factors leading to the rise and fall of the peshat method has been undertaken, and most academic attention to the subject has focused on particular aspects, specifically the question of the factors that led to the flourishing of the peshat method in northern France. In this study, I fill this gap. As will be made clear, my results differ in various points from the views presented in previous research.
Bark and wood anatomy of Leucosidea and Cliffortia (Sanguisorbeae, Rosaceae)
Authors: Kotina Ekaterina L. , Oskolski Alexei A. , Tilney Patricia M. , Van Wyk Ben-Erik
Published: February 2017

The wood and bark structure of Leucosidea sericea and two species of Cliffortia, the South African members of the tribe Sanguisorbeae (Rosaceae) are described. These two genera share few anatomical traits (the presence of schizo-rhexigenous intercellular spaces in the cortex, almost exclusively simple perforation plates, small alternate intervessel pits, etc.) with other Rosaceae. However, Leucosidea shows a distinct storied structure of the secondary phloem and wood as well as stratification of the secondary phloem, with conductive elements and nonsclerified crystalliferous axial parenchyma arranged into alternating bands. These conditions are recorded for the first time for the family Rosaceae. In contrast to Leucosidea, two species of Cliffortia show neither storied structure of secondary phloem and xylem, nor stratification of secondary phloem.
Structure and ontogeny of the fissured stems of Callaeum (Malpighiaceae)
Authors: Cabanillas Pablo A. , Pace Marcelo R. , Angyalossy Veronica
Published: February 2017

Stem ontogeny and structure of two neotropical twining vines of the genus Callaeum are described. Secondary growth in Callaeum begins with a typical regular cambium that gradually becomes lobed as a result of variation in xylem and phloem production rates in certain portions of the stem aligned with stem orthostichies. As development progresses, lignified ray cells of the initially formed secondary xylem detach on one side from the adjacent tissues, forming a natural fracture that induces the proliferation of both ray and axial nonlignified parenchyma. At the same time, parenchyma proliferation takes place around the pith margin and generates a ring of radially arranged parenchyma cells. The parenchyma generated in this process (here termed disruptive parenchyma) keeps dividing throughout stem development. As growth continues, the parenchyma finally cleaves the lignified axial parts of the vascular system into several isolated fragments of different sizes. Each fragment consists of xylem, phloem and vascular cambium and is immersed in a ground matrix of disruptive parenchyma. The cambium present in each fragment divides anticlinally to almost encircle each entire fragment and maintains its regular activity by producing xylem to the centre of the fragment and phloem to the periphery. Additionally, new cambia arise within the disruptive parenchyma and produce xylem and phloem in various polarities, such as xylem to the inside and phloem to the outside of the stem, or perpendicularly to the original cambium. Unlike the very distinctive stem anatomical architecture resulting from this cambial variant in Callaeum, its secondary xylem and phloem exhibit features typical of lianas. These features include very wide conducting cells, abundant axial parenchyma, high and heterocellular rays and gelatinous fibres.
A new species of Lysipomia (Campanulaceae) from Ecuador
Authors: AYERS TINA J. , SKLENÁŘ PETR , FERNÁNDEZ DIANA M.
Published: February 2017

Lysipomia petrosa from Azuay province, Ecuador, is described as new and compared with the related species L. bilineata and L. caespitosa.
New names in Aralia (Araliaceae), living and fossil
Authors: DOWELD ALEXANDER B.
Published: February 2017

The nomenclature of some fossil and extant homonymic species of Aralia is resolved. Aralia laevis J. Wen (extant) is replaced by a new name A. indonesica nom. nov., because of earlier homonym, A. laevis E.M.Reid (fossil). Aralia debilis J. Wen is rehabilitated as a legitimate substitute to the later homonym, A. elegans Ho, due to the existence of several earlier homonyms, the extant A. elegans Linden ex Koch, A. elegans Cunn. ex W.Hill and A. elegans Hort. ex Saporta, and the fossil A. elegans Velenovský. Additional four new replacement names are proposed for fossil species based on endocarp remains from the Miocene sediments of Siberia: Aralia asiatica nom. nov. for A. rugosa Dorofeev non Blume, A. mammuthica nom. nov. for A. dubia V.P. Nikitin non Sprengel nec Fontaine, A. borealis nom. nov. for A. tertiaria Dorofeev non Pilar, and A. tobolica nom. nov. for A. lucida Dorofeev non Hasskarl. The later homonym A. angustiloba Kolakovsky non Lesquereux, based on the fossil foliage from the Pliocene sediments of Transcaucasus, is transferred into Brassaiopsis as B. kolakovskyana nom. nov. Fossil species A. furcata, described on the basis of leaf remains from the Upper Cretaceous (Cenomanian) of Bohemia, is transferred into Haliserites as H. furcatus comb. nov. The fossil later homonym A. serrata Knowlton non Saporta, described on the basis of leaf remains from the Palaeocene of North America, is transferred into Platanus as P. serrata nom. nov.