bluuebunny/crossref_metadata_2025 huggingface dataset:
The Oxylipin Pathways: Biochemistry and Function
Authors: Wasternack Claus , Feussner Ivo
Published: November 2017

Plant oxylipins form a constantly growing group of signaling molecules that comprise oxygenated fatty acids and metabolites derived therefrom. In the last decade, the understanding of biosynthesis, metabolism, and action of oxylipins, especially jasmonates, has dramatically improved. Additional mechanistic insights into the action of enzymes and insights into signaling pathways have been deepened for jasmonates. For other oxylipins, such as the hydroxy fatty acids, individual signaling properties and cross talk between different oxylipins or even with additional phytohormones have recently been described. This review summarizes recent understanding of the biosynthesis, regulation, and function of oxylipins.
Three-dimensional imaging reveals endo(sarco)plasmic reticulum-containing invaginations within the nucleoplasm of muscle
Authors: Lee Shin-Haw , Hadipour-Lakmehsari Sina , Miyake Tetsuaki , Gramolini Anthony O.
Published: November 2017

The mammalian nucleus has invaginations from the cytoplasm, termed nucleoplasmic reticulum (NR). With increased resolution of cellular imaging, progress has been made in understanding the formation and function of NR. In fact, nucleoplasmic Ca2+ homeostasis has been implicated in the regulation of gene expression, DNA repair, and cell death. However, the majority of studies focus on cross-sectional or single-plane analyses of NR invaginations, providing an incomplete assessment of its distribution and content. Here, we provided advanced imaging and three-dimensional reconstructive analyses characterizing the molecular constituents of nuclear invaginations in the nucleoplasm in HEK293 cells, murine C2C12 muscle cells, and cardiac myocytes. We demonstrated the presence of critical Ca2+ regulatory channels, including sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), stromal interaction molecule 1 (STIM1), and Ca2+ release-activated Ca2+ channel protein 1 (ORAI1), in the nucleoplasm in isolated primary mouse cardiomyocytes. We have shown for the first time the presence of STIM1 and ORAI1 in the nucleoplasm, suggesting the presence of store-operated calcium entry (SOCE) mechanism in nucleoplasmic Ca2+ regulation. These results show that nucleoplasmic invaginations contain continuous endoplasmic reticulum components, mitochondria, and intact nuclear membranes, highlighting the extremely detailed and complex nature of this organellar structure.
Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats
Authors: Nakamori Hiroyuki , Naitou Kiyotada , Horii Yuuki , Shimaoka Hiroki , Horii Kazuhiro , Sakai Hiroki , Yamada Akihiro , Furue Hidemasa , Shiina Takahiko , Shimizu Yasutake
Published: November 2017

Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the lumbosacral defecation center.

NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.
Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca2+ signals and contraction in fetal and adult sheep
Authors: Shen Christine P. , Romero Monica , Brunelle Alexander , Wolfe Craig , Dobyns Abigail , Francis Michael , Taylor Mark S. , Puglisi Jose L. , Longo Lawrence D. , Zhang Lubo , Wilson Christopher G. , Wilson Sean M.
Published: November 2017

Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca2+ signaling is important during the development of LTH-induced pulmonary hypertension. In the present study, we tested the hypothesis that L-type Ca2+ channels (CaL), which are voltage dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in postnatal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low or high altitude (3,801 m) for >100 days. The effects were measured using an L-type Ca2+ channel opener FPL 64176 (FPL) in the presence or absence of an inhibitor, Nifedipine (NIF) on arterial contractions, intracellular Ca2+ oscillations, and ryanodine receptor-driven Ca2+ sparks. FPL induced pulmonary arterial contractions in all groups were sensitive to NIF. However, when compared with 125 mM K+, FPL contractions were greater in fetuses than in adults. FPL reduced Ca2+ oscillations in myocytes of adult but not fetal arteries, independently of altitude. The FPL effects on Ca2+ oscillations were reversed by NIF in myocytes of hypoxic but not normoxic adults. FPL failed to enhance Ca2+ spark frequency and had little impact on spatiotemporal firing characteristics. These data suggest that CaL-dependent contractions are largely uncoupled from intracellular Ca2+ oscillations and the development of Ca2+ sparks. This raises questions regarding the coupling of pulmonary arterial contractility to membrane depolarization, attendant CaL facilitation, and the related associations with the activation of Ca2+ oscillations and Ca2+ sparks.
Blood-borne interleukin-1β acts on the subfornical organ to upregulate the sympathoexcitatory milieu of the hypothalamic paraventricular nucleus
Authors: Wei Shun-Guang , Yu Yang , Felder Robert B.
Published: November 2017

We previously reported that microinjection of the proinflammatory cytokine interleukin-1β (IL-1β) into the subfornical organ (SFO) elicits a pressor response accompanied by increases in inflammation and renin-angiotensin system (RAS) activity in the SFO and hypothalamic paraventricular nucleus (PVN). The present study sought to determine whether blood-borne IL-1β induces similar neurochemical changes in the SFO and PVN and, if so, whether increased inflammation and RAS activity at the SFO level orchestrate the sympathoexcitatory response to circulating IL-1β. In urethane-anesthetized male Sprague-Dawley rats, intravenous injection of IL-1β (500 ng) increased blood pressure, heart rate, renal sympathetic nerve activity, and mRNA for angiotensin-converting enzyme, angiotensin II type 1a receptor, cyclooxygenase-2, tumor necrosis factor-α, and IL-1β, as well as the tumor necrosis factor-α p55 receptor and the IL-1 receptor, in the SFO and PVN. Pretreatment with SFO microinjections of the angiotensin II type 1a receptor blocker losartan (1 µg), the angiotensin-converting enzyme inhibitor captopril (1 µg), or the cyclooxygenase-2 inhibitor NS-398 (2 µg) attenuated expression of these excitatory mediators in the SFO and downstream in the PVN and the IL-1β-induced pressor responses. An SFO lesion minimized the IL-1β-induced expression of inflammatory and RAS components as well as c-Fos, an indicator of neuronal excitation, in the PVN. These studies demonstrate that circulating IL-1β, which increases in cardiovascular disorders such as hypertension and heart failure, acts on the SFO to increase inflammation and RAS activity in the SFO and PVN and that intervening in these neurochemical processes in the SFO can significantly reduce the sympathetic response.
Cutting-edge microangio-CT: new dimensions in vascular imaging and kidney morphometry
Authors: Hlushchuk Ruslan , Zubler Cédric , Barré Sébastien , Correa Shokiche Carlos , Schaad Laura , Röthlisberger Raphael , Wnuk Monika , Daniel Christoph , Khoma Oleksiy , Tschanz Stefan A. , Reyes Mauricio , Djonov Valentin
Published: November 2017

In the last decades, the contrast-enhanced micro-computed tomography (micro-CT) imaging of a whole animal kidney became increasingly important. The visualization was mainly limited to middle-sized vessels. Since modern desktop micro-CT scanners provide the necessary detail resolution, we developed an approach for rapid visualization and consistent assessment of kidney vasculature and glomeruli number. This method is based on μAngiofil, a new polymerizing contrast agent with homogenous X-ray absorption, which provides continuous filling of the complete vasculature and enables correlative imaging approaches. For rapid and reliable kidney morphometry, the microangio-CT (µaCT) data sets from glial cell line-derived neurotrophic factor (GDNF)+/−mice and their wild-type littermates were used. The results were obtained much faster compared with the current gold standard, histology-based stereology, and without processing artifacts. The histology-based morphometry was done afterward on the same kidneys. Both approaches revealed that the GDNF+/−male mice had about 40% fewer glomeruli. Furthermore, our approach allows for the definition of sites of interest for further histological investigation, i.e., correlative morphology. The polymerized μAngiofil stays in perfused vessels and is autofluorescent, which is what greatly facilitates the matching of histological sections with µaCT data. The presented approach is a time-efficient, reliable, qualitative, and quantitative methodology. Besides glomerular morphometry, the µaCT data can be used for qualitative and quantitative analysis of the kidney vasculature and correlative morphology.
Advances in our understanding of the pathogenesis of hemolytic uremic syndromes
Authors: Bowen E. E. , Coward R. J.
Published: November 2017

Hemolytic uremic syndrome (HUS) is major global health care issue as it is the leading cause of acute kidney injury in children. It is a triad of acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. In recent years, major advances in our understanding of complement-driven inherited rare forms of HUS have been achieved. However, in children 90% of cases of HUS are associated with a Shiga toxin-producing enteric pathogen. The precise pathological mechanisms in this setting are yet to be elucidated. The purpose of this review is to discuss advances in our understanding of the pathophysiology underlying HUS and identify the key questions yet to be answered by the scientific community.
Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice
Authors: Konstantoudaki Xanthippi , Chalkiadaki Kleanthi , Vasileiou Elisabeth , Kalemaki Katerina , Karagogeos Domna , Sidiropoulou Kyriaki
Published: November 2017

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty-seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC, particularly compared with other primary cortical areas. This study aims to understand the development of PFC-mediated, compared with non-PFC-mediated, cognitive functions. Toward this aim, we performed cognitive behavioral tasks in adolescent and adult mice and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared with adult mice, whereas their performance in non-PFC-dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel cortex. Blocking GABAA receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents.

NEW & NOTEWORTHY This study reports that adolescent mice exhibit impaired performance in cognitive functions dependent on the prefrontal cortex but not in cognitive functions dependent on other cortical regions. The current results propose reduced synaptic plasticity in the upper layers of the prefrontal cortex as a cellular correlate of this weakened cognitive function. This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate receptor expression but not due to dampened intrinsic excitability or enhanced GABAergic signaling during adolescence.
Impact of spatiotemporal calcium dynamics within presynaptic active zones on synaptic delay at the frog neuromuscular junction
Authors: Homan Anne E. , Laghaei Rozita , Dittrich Markus , Meriney Stephen D.
Published: November 2017

The spatiotemporal calcium dynamics within presynaptic neurotransmitter release sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for shaping the dynamics of neurotransmitter release. Specifically, the relative arrangement and density of voltage-gated calcium channels (VGCCs) as well as the concentration of calcium buffering proteins can play a large role in the timing, magnitude, and plasticity of release by shaping the AZ calcium profile. However, a high-resolution understanding of the role of AZ structure in spatiotemporal calcium dynamics and how it may contribute to functional heterogeneity at an adult synapse is currently lacking. We demonstrate that synaptic delay varies considerably across, but not within, individual synapses at the frog neuromuscular junction (NMJ). To determine how elements of the AZ could contribute to this variability, we performed a parameter search using a spatially realistic diffusion reaction-based computational model of a frog NMJ AZ (Dittrich M, Pattillo JM, King JD, Cho S, Stiles JR, Meriney SD. Biophys J 104: 2751–2763, 2013; Ma J, Kelly L, Ingram J, Price TJ, Meriney SD, Dittrich M. J Neurophysiol 113: 71–87, 2015). We demonstrate with our model that synaptic delay is sensitive to significant alterations in the spatiotemporal calcium dynamics within an AZ at the time of release caused by manipulations of the density and organization of VGCCs or by the concentration of calcium buffering proteins. Furthermore, our data provide a framework for understanding how AZ organization and structure are important for understanding presynaptic function and plasticity.

NEW & NOTEWORTHY The structure of presynaptic active zones (AZs) can play a large role in determining the dynamics of neurotransmitter release across many model preparations by influencing the spatiotemporal calcium dynamics within the AZ at the time of vesicle fusion. However, less is known about how different AZ structural schemes may influence the timing of neurotransmitter release. We demonstrate that variations in AZ structure create different spatiotemporal calcium profiles that, in turn, lead to differences in synaptic delay.
The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma
Authors: Izuhara Kenji , Suzuki Shoichi , Ogawa Masahiro , Nunomura Satoshi , Nanri Yasuhiro , Mitamura Yasutaka , Yoshihara Tomohito
Published: November 2017

Inhaled corticosteroids (ICSs) are used as first‐line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL‐13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN−) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN−) into pulmonary lumens at the apical side. Peroxidases catalyze SCN− and H2O2 generated by DUOX into OSCN−. Low doses of OSCN− activate NF‐κB in airway epithelial cells, whereas OSCN− in high doses causes necrosis of the cells, inducing the release of IL‐33 and accelerating inflammation. OSCN− production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma‐like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.
SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV
Authors: Gonzalez-Enriquez Gracia Viviana , Escoto-Delgadillo Martha , Vazquez-Valls Eduardo , Torres-Mendoza Blanca Miriam
Published: November 2017

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.
Anticoagulation for the Pregnant Patient with a Mechanical Heart Valve, No Perfect Therapy: Review of Guidelines for Anticoagulation in the Pregnant Patient
Authors: Richardson Aaron , Shah Stuart , Harris Ciel , McCulloch Garry , Antoun Patrick
Published: November 2017

Heart valve replacement with a mechanical valve requires lifelong anticoagulation. Guidelines currently recommend using a vitamin K antagonist (VKA) such as warfarin. Given the teratogenic effects of VKAs, it is often favorable to switch to heparin-derived therapies in pregnant patients since they do not cross the placenta. However, these therapies are known to be less effective anticoagulants subjecting the pregnant patient to a higher chance of a thrombotic event. Guidelines currently recommend pregnant women requiring more than 5 mg a day of warfarin be switched to alternative therapy during the first trimester. This case report highlights a patient who was switched to alternative therapy during her first pregnancy and suffered a devastating cerebrovascular accident (CVA). Further complicating her situation was during a subsequent pregnancy; this patient continued warfarin use during the first trimester and experienced multiple transient ischemic attacks (TIAs). This case highlights the increased risk of thrombotic events in pregnant patients with mechanical valves. It also highlights the difficulty of providing appropriate anticoagulation for the pregnant patient who has experienced thrombotic events on multiple anticoagulants.
Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles and Their Curative Effect on the Tumor Microenvironment
Authors: Maritim Samuel , Coman Daniel , Huang Yuegao , Rao Jyotsna U. , Walsh John J. , Hyder Fahmeed
Published: November 2017

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH (pHe) is a tumor hallmark, mappingpHeis critical. BrainpHeis measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-basedpHereadout remains uncompromised by presence of SPIO-NPs, we mappedpHein glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, thepHeinside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-basedpHecan map their therapeutic impact.
Active Fragment of Veronica ciliata Fisch. Attenuates t‐BHP‐Induced Oxidative Stress Injury in HepG2 Cells through Antioxidant and Antiapoptosis Activities
Authors: Sun Yiran , Lu Qiuxia , He Libo , Shu Yueyue , Zhang Shiyan , Tan Shancai , Tang Lin
Published: November 2017

Excessive amounts of reactive oxygen species (ROS) in the body are a key factor in the development of hepatopathies such as hepatitis. The aim of this study was to assess the antioxidation effect in vitro and hepatoprotective activity of the active fragment of Veronica ciliata Fisch. (VCAF). Antioxidant assays (DPPH, superoxide, and hydroxyl radicals scavenging) were conducted, and hepatoprotective effects through the application of tert‐butyl hydroperoxide‐ (t‐BHP‐) induced oxidative stress injury in HepG2 cells were evaluated. VCAF had high phenolic and flavonoid contents and strong antioxidant activity. From the perspective of hepatoprotection, VCAF exhibited a significant protective effect on t‐BHP‐induced HepG2 cell injury, as indicated by reductions in cytotoxicity and the levels of ROS, 8‐hydroxydeoxyguanosine (8‐OHdG), and protein carbonyls. Further study demonstrated that VCAF attenuated the apoptosis of t‐BHP‐treated HepG2 cells by suppressing the activation of caspase‐3 and caspase‐8. Moreover, it significantly decreased the levels of ALT and AST, increased the activities of acetyl cholinesterase (AChE), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), and increased total antioxidative capability (T‐AOC). Collectively, we concluded that VCAF may be a considerable candidate for protecting against liver injury owing to its excellent antioxidant and antiapoptosis properties.
Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice
Authors: Ye Jing , Liu Ling , Ji Qingwei , Huang Ying , Shi Ying , Shi Lei , Liu Jianfang , Wang Menglong , Xu Yao , Jiang Huimin , Wang Zhen , Lin Yingzhong , Wan Jun
Published: November 2017

Background. Interleukin- (IL-) 22 is considered a proinflammatory cytokine. Recent evidence has demonstrated that it plays a role in cardiovascular diseases. In the recent study, we investigate whether IL-22 is involved in cardiac hypertrophy. Methods. Angiotensin II was used to build hypertrophy model and the IL-22 and IL-22 receptor 1 (IL-22R1) levels in heart tissue were measured. In addition, angiotensin II-treated mice received an injection of anti-IL-22-neutralizing antibody (nAb) to investigate the effects of IL-22 nAb on myocardial hypertrophy, cardiac function, and cardiac fibrosis; the activation of the signaling pathway and the prohypertrophic inflammatory cytokine mRNA levels was detected. Furthermore, the effect of IL-22 nAb on angiotensin II-induced hypertrophy in vitro was also determined. Results. IL-22 and IL-22R1 levels were significantly increased after angiotensin II infusion. Anti-IL-22 nAb significantly alleviated the severity of hypertrophy, prevented systolic and diastolic abnormalities, reduced cardiac fibrosis, STAT3 and ERK phosphorylation, and downregulated the mRNA expression of IL-17, IL-6, IL-1β, IFN-γ, and TNF-α. In addition, IL-22 nAb attenuated angiotensin II-induced hypertrophy in H9C2 cells. Conclusion. Our data demonstrated that neutralization of IL-22 alleviated angiotensin II-induced cardiac hypertrophy. The downregulation of IL-22 may be a novel therapeutic strategy to prevent cardiac hypertrophy.
Regulation of Reentrainment Function Is Dependent on a Certain Minimal Number of Intact Functional ipRGCs in rd Mice
Authors: Zhang Jingxue , Wang Huaizhou , Wu Shen , Liu Qian , Wang Ningli
Published: November 2017

Purpose. To investigate the effect of partial ablation of melanopsin-containing retinal ganglion cells (mcRGCs) on nonimage-forming (NIF) visual functions in rd mice lacking rods.Methods. The rd mice were intravitreally injected with different doses (100 ng/μl, 200 ng/μl, and 400 ng/μl) of immunotoxin melanopsin-SAP. And then, the density of ipRGCs was examined. After establishing the animal models with different degrees of ipRGC damage, a wheel-running system was used to evaluate their reentrainment response.Results. Intravitreal injection of melanopsin-SAP led to partial ablation of ipRGCs in a dose-dependent manner. The survival rates of ipRGCs in the 100 ng/μl, 200 ng/μl, and 400 ng/μl groups were 74.14% ± 4.15%, 39.25% ± 2.29%, and 38.38% ± 3.74%, respectively. The wheel-running experiments showed that more severe ipRGC loss was associated with a longer time needed for reentrainment. When the light/dark cycle was delayed by 8 h, the rd mice in the PBS control group took 4.67 ± 0.79 days to complete the synchronization with the shifted cycle, while those in the 100 ng/μl and 200 ng/μl groups required 7.90 ± 0.55 days and 11.00 ± 0.79 days to complete the synchronization with the new light/dark cycle, respectively.Conclusion. Our study indicates that the regulation of some NIF visual functions is dependent on a certain minimal number of intact functional ipRGCs.
Exercise Combined with Rhodiola sacra Supplementation Improves Exercise Capacity and Ameliorates Exhaustive Exercise‐Induced Muscle Damage through Enhancement of Mitochondrial Quality Control
Authors: Dun Yaoshan , Liu Suixin , Zhang Wenliang , Xie Murong , Qiu Ling
Published: November 2017

Mounting evidence has firmly established that increased exercise capacity (EC) is associated with considerable improvements in the survival of patients with cardiovascular disease (CVD) and that antistress capacity is a prognostic predictor of adverse cardiovascular events in patients with CVD. Previous studies have indicated that aerobic exercise (AE) and supplementation with Rhodiola sacra (RS), a natural plant pharmaceutical, improve EC and enable resistance to stress; however, the underlying mechanism remains unclear. This study explored the ability of AE and RS, alone or combined, to improve EC and ameliorate exhaustive exercise‐ (EE‐) induced stress and elucidate the mechanism involved. We found that AE and RS significantly increased EC in mice and ameliorated EE‐induced stress damage in skeletal and cardiac muscles (SCM); furthermore, a synergistic effect was detected for the first time. To our knowledge, the present work is the first to report that AE and RS activate mitophagy, mitochondrial dynamics, and biogenesis in SCM, both in the resting state and after EE. These data indicate that AE and RS synergistically improve EC in mice and protect SCM from EE‐induced stress by enhancing mitochondrial quality control, including the activation of mitophagy, mitochondrial dynamics, and biogenesis, both at rest and after EE.
Estimation of Impact Loads in a Hydraulic Breaker by Transfer Path Analysis
Authors: Song Changheon , Kim Dae Ji , Chung Jintai , Lee Kang Won , Kweon Sang Seuk , Kang Young Ky
Published: November 2017

The aim of this study is to estimate the impact loads delivered to the housing of a hydraulic breaker quantitatively. Striking forces caused vibrations in the equipment housing, which were experimentally measured, and frequency response functions were also found through modal impact experiments. Transfer path analysis (TPA) method of the data quantified the impact loads delivered to the housing. TPA method can analyze the relationship between the vibration energy and the transfer path of an excitation source and so explore the way in which vibrations on each path contribute to the entire vibration profile. The impact loads of each part derived by TPA method were compared with the impact loads in the chisel derived from strain gauge measurements of the striking energy. This comparison validated the TPA approach. This study describes the basic concepts and components of TPA method and also reviews its applicability to mechanical equipment that experiences impact vibrations and impact loads.
Quantitative Aspect of Leucophyllum frutescens Fraction before and after Encapsulation in Polymeric Nanoparticles
Authors: Martínez-Rivas Claudia Janeth , Álvarez-Román Rocío , Rivas-Morales Catalina , Elaissari Abdelhamid , Fessi Hatem , Galindo-Rodríguez Sergio Arturo
Published: November 2017

The interest on plants has been focalized due to their biological activities. Extracts or fractions from plants in biodegradable polymeric nanoparticles (NP) provide many advantages on application studies. The encapsulation of the extract or fraction in NP is determined for the establishment of the test dose. HPLC method is an alternative to calculate this parameter. An analytical method based on HPLC for quantification of a hexane fraction from L. frutescens was developed and validated according to ICH. Different concentrations of the hexane fraction from leaves (HFL) were prepared (100–600 μg/mL). Linearity, limit of detection, limit of quantification, and intra- and interday precision parameters were determined. HFL was encapsulated by nanoprecipitation technique and analyzed by HPLC for quantitative aspect. The method was linear and precise for the quantification of the HFL components. NP size was 190 nm with homogeneous size distribution. Through validation method, it was determined that the encapsulation of components (1), (2), (3), and (4) was 44, 74, 86, and 97%, respectively. A simple, repeatable, and reproducible methodology was developed for the propose of quantifying the components of a vegetable material loaded in NP, using as a model the hexane fraction of L. frutescens leaves.
Towards Large-Scale, Heterogeneous Anomaly Detection Systems in Industrial Networks: A Survey of Current Trends
Authors: Iturbe Mikel , Garitano Iñaki , Zurutuza Urko , Uribeetxeberria Roberto
Published: November 2017

Industrial Networks (INs) are widespread environments where heterogeneous devices collaborate to control and monitor physical processes. Some of the controlled processes belong to Critical Infrastructures (CIs), and, as such, IN protection is an active research field. Among different types of security solutions, IN Anomaly Detection Systems (ADSs) have received wide attention from the scientific community. While INs have grown in size and in complexity, requiring the development of novel, Big Data solutions for data processing, IN ADSs have not evolved at the same pace. In parallel, the development of Big Data frameworks such as Hadoop or Spark has led the way for applying Big Data Analytics to the field of cyber-security, mainly focusing on the Information Technology (IT) domain. However, due to the particularities of INs, it is not feasible to directly apply IT security mechanisms in INs, as IN ADSs face unique characteristics. In this work we introduce three main contributions. First, we survey the area of Big Data ADSs that could be applicable to INs and compare the surveyed works. Second, we develop a novel taxonomy to classify existing IN-based ADSs. And, finally, we present a discussion of open problems in the field of Big Data ADSs for INs that can lead to further development.
Blood Pressure Status in Adult Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study
Authors: Gibson Todd M. , Li Zhenghong , Green Daniel M. , Armstrong Gregory T. , Mulrooney Daniel A. , Srivastava DeoKumar , Bhakta Nickhill , Ness Kirsten K. , Hudson Melissa M. , Robison Leslie L.
Published: November 2017

Background: Hypertension potentiates cardiovascular risk in survivors of childhood cancer previously exposed to cardiotoxic therapies, so it is important to determine the prevalence and risk factors for hypertensive blood pressure in this high-risk group.

Methods: Participants included 3,016 adult 10-year survivors of childhood cancer who had resting blood pressure measurements performed at St. Jude Children's Research Hospital (Memphis, TN). We characterized the blood pressure status of participants, calculated standardized prevalence ratios based on U.S. population rates, and examined demographic and treatment factors associated with hypertensive blood pressure using logistic regression.

Results: The age-specific cumulative prevalence of hypertension in survivors increased sharply with age, exceeding 70% by age 50, and was substantially higher in all diagnosis groups than expected on the basis of age-, sex-, race/ethnicity-, and BMI-specific population rates. Specific cancer treatments were not significantly associated with hypertension, with the exception of nephrectomy (OR, 1.68; 95% confidence interval, 1.11–2.53). Previously undiagnosed hypertensive blood pressure was identified in 8% of survivors, and uncontrolled hypertension in 22% of those with a previous hypertension diagnosis. In a subset (n = 1,185) with longitudinal blood pressure measurements (mean interval, 3.6 years), 5% and 21% of participants with previously normal blood pressure developed hypertensive and prehypertensive blood pressure, respectively.

Conclusions: Survivors of childhood cancer have a higher prevalence of hypertension compared with the general population, and many have uncontrolled hypertension that may exacerbate treatment-related cardiovascular risks.

Impact: Our results suggest enhanced clinical attention to blood pressure status is warranted in all survivors, regardless of diagnosis or cancer treatment. Cancer Epidemiol Biomarkers Prev; 26(12); 1705–13. ©2017 AACR.
Lactic Acid Bacteria from Andean Grain Amaranth: A Source of Vitamins and Functional Value Enzymes
Authors: Carrizo Silvana L. , Montes de Oca Cecilia E. , Hébert María Elvira , Saavedra Lucila , Vignolo Graciela , LeBlanc Jean Guy , Rollán Graciela Celestina
Published: November 2017

Amaranth is a rediscovered pseudocereal with high nutritional properties. Lactic acid fermentation can increase the functional and nutritional value of foods. The aims of this study were to isolate and evaluate the functionality of lactic acid bacteria (LAB) from amaranth. LAB strains (n = 29) isolated from amaranth sourdough and grains included Lactobacillus (L.) plantarum (n = 8), L. rhamnosus (n = 6), Enterococcus (E.) mundtii (n = 4), E. hermanniensis (n = 3), E. durans (n = 1), Enterococcus sp. (n = 1), Leuconostoc (Lc.) mesenteroides (n = 3), and Lc. mesenteroides subsp. mesenteroides (n = 3). Only 21% of the strains showed the ability to synthesize capsular exopolysaccharides or display ropiness and only 8 strains showed amylolytic activity. L. plantarum CRL 2106 and E. durans CRL 2122 showed the highest phytase activity, which is of importance for mineral bioavailability. L. plantarum CRL 2106 and CRL 2107 and Lc. mesenteroides subsp. mesenteroides CRL 2131 synthesized the highest concentrations of B2 and B9 vitamin (140-250 ng/mL). This study demonstrates the potential of LAB to improve the nutritional and functional values of pseudocereal-derived foods.
Angiotensin II Infusion Does Not Cause Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Rats
Authors: Phillips Evan H. , Chang Mandy S. , Gorman Sydney , Qureshi Hamna J. , Ejendal Karin F.K. , Kinzer-Ursem Tamara L. , Blaize A. Nicole , Goergen Craig J.
Published: November 2017

The apolipoprotein E-deficient (apoE-/-) mouse model has advanced our understanding of cardiovascular disease mechanisms and experimental therapeutics. This spontaneous model recapitulates aspects of human atherosclerosis, and allows for the development of dissecting abdominal aortic aneurysms (AAAs) when combined with angiotensin II. We characterized apoE-/- rats and hypothesized that, similar to mice, they would develop dissecting AAAs. We created rats with a 16-bp deletion of the apoE gene using transcription activator-like effector nucleases. We imaged the suprarenal aorta for 28 days after implantation of miniosmotic pumps that infuse angiotensin II (AngII, 200 ng/kg/min). Blood pressure (BP), serum lipids and lipoproteins, and histology were also analyzed. These rats did not develop pathological aortic dissection, but we did observe a decrease in circumferential cyclic strain, a rise in BP, and microstructural changes in the aortic medial layer. We also measured increased serum lipids with and without administration of a high-fat diet, but did not detect atherosclerotic plaques. Chronic infusion of AngII did not lead to the formation of dissecting AAAs or atherosclerosis in the rats used in this study. While reduced amounts of atherosclerosis may explain this resistance to dissecting aneurysms, further investigation is needed to fully characterize species-specific differences.
Predictors of Surgical Outcomes of Traumatic Peripheral Nerve Injuries in Children: An Institutional Experience
Authors: Devi Bhagavatula Indira , Konar Subhas K. , Bhat Dhananjaya I. , Shukla Dhaval P. , Bharath R. , Gopalakrishnan M.S.
Published: November 2017

Aim: This study was undertaken to address the epidemiological characteristics, operative details, and surgical outcome of peripheral nerve injuries in children treated in a tertiary hospital in India (NIMHANS, Bangalore). Materials and Methods: This is a retrospective study of epidemiology, operative findings, and surgical outcomes over the period of 2000-2016. Our series includes 102 children with peripheral nerve injuries of various causes. Results: Intramuscular injections were the most common cause (52.9%), followed by entrapment (15.6%). The most common nerve involved was the sciatic nerve (54.9%), followed by the common peroneal nerve (13.7%), the ulnar nerve (10.8%), and the radial nerve (10.8%). Perineural adhesion was the most common intraoperative finding (74.5%), followed by a neuroma in continuity (14.7%) and gap (10.8%). Most of the children with peripheral adhesion underwent external and internal neurolysis (75.5%). Follow-up was available for 67 children. The median follow-up period was 7 months (range 3-36). The outcome was assessed according to MRC grading. Favorable functional improvement was noted in 76.1% of the children. Age less than 10 years (p = 0. 06), injury before 6 months (p = 0.03), and MRC motor grade (<3) (p = 0. 01) were positive predictive factors related to the final outcome. Conclusion: Early surgical intervention, age less than 10 years, and incomplete motor palsy were the best predictors of a superior functional outcome. This study can serve as a guide to determine the epidemiology, duration of intervention, and surgical outcome of traumatic peripheral nerve injuries in the pediatric population
Distinct Cellular Mechanisms Underlie Smooth Muscle Turnover in Vascular Development and Repair
Authors: Roostalu Urmas , Aldeiri Bashar , Albertini Alessandra , Humphreys Neil , Simonsen-Jackson Maj , Wong Jason K.F. , Cossu Giulio
Published: November 2017

Rationale:

Vascular smooth muscle turnover has important implications for blood vessel repair and for the development of cardiovascular diseases, yet lack of specific transgenic animal models has prevented it’s in vivo analysis.

Objective:

The objective of this study was to characterize the dynamics and mechanisms of vascular smooth muscle turnover from the earliest stages of embryonic development to arterial repair in the adult.

Methods and Results:

We show that CD146 is transiently expressed in vascular smooth muscle development. By using CRISPR-Cas9 genome editing and in vitro smooth muscle differentiation assay, we demonstrate that CD146 regulates the balance between proliferation and differentiation. We developed a triple-transgenic mouse model to map the fate of NG2
+
CD146
+
immature smooth muscle cells. A series of pulse-chase experiments revealed that the origin of aortic vascular smooth muscle cells can be traced back to progenitor cells that reside in the wall of the dorsal aorta of the embryo at E10.5. A distinct population of CD146
+
smooth muscle progenitor cells emerges during embryonic development and is maintained postnatally at arterial branch sites. To characterize the contribution of different cell types to arterial repair, we used 2 injury models. In limited wire-induced injury response, existing smooth muscle cells are the primary contributors to neointima formation. In contrast, microanastomosis leads to early smooth muscle death and subsequent colonization of the vascular wall by proliferative adventitial cells that contribute to the repair.

Conclusions:

Extensive proliferation of immature smooth muscle cells in the primitive embryonic dorsal aorta establishes the long-lived lineages of smooth muscle cells that make up the wall of the adult aorta. A discrete population of smooth muscle cells forms in the embryo and is postnatally sustained at arterial branch sites. In response to arterial injuries, existing smooth muscle cells give rise to neointima, but on extensive damage, they are replaced by adventitial cells.
Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation
Authors: Proietti Marco , Romanazzi Imma , Romiti Giulio Francesco , Farcomeni Alessio , Lip Gregory Y.H.
Published: November 2017

Background and Purpose—

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.

Methods—

We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.

Results—

From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64–0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (
P
<0.00001 for all comparisons).

Conclusions—

Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.
Prehospital Systolic Blood Pressure Is Related to Intracerebral Hemorrhage Volume on Admission
Authors: Rodriguez-Luna David , Rodriguez-Villatoro Noelia , Juega Jesús M. , Boned Sandra , Muchada Marián , Sanjuan Estela , Pagola Jorge , Rubiera Marta , Ribo Marc , Coscojuela Pilar , Molina Carlos A.
Published: November 2017

Background and Purpose—

Ultra-early blood pressure (BP) management in the prehospital setting could improve the efficacy of this treatment on attenuating intracerebral hemorrhage (ICH) expansion. We aimed to determine the association of prehospital systolic BP (SBP) with ICH volume, ultra-early hematoma growth, and the spot sign on admission.

Methods—

We conducted a retrospective study of a prospective database of 219 consecutive patients with spontaneous ICH admitted to the emergency department of a tertiary stroke center during a 3-year period. Prehospital SBP and ICH volume, ultra-early hematoma growth (ICH volume/onset-to-imaging time), and presence of the spot sign on admission were prospectively recorded. Primary outcome was ICH volume on admission. Secondary outcomes included ultra-early hematoma growth and frequency of the spot sign in patients scanned within 6 hours from symptom onset (hyperacute group).

Results—

Prehospital SBP was positively correlated with both SBP (
r
=0.552;
P
<0.001) and ICH volume (ρ=0.189;
P
=0.006) on admission. Patients with ICH volume above the median value presented higher prehospital SBP (172.3±35.0 versus 163.7±27.8 mm Hg;
P
=0.049). This association remained significant in adjusted multiple logistic regression analysis (odds ratio, 1.01 for a 1-U increase in SBP; 95% confidence interval, 1.01–1.02;
P
=0.018). In the hyperacute group (n=126), prehospital SBP was unrelated to ultra-early hematoma growth (ρ=0.115;
P
=0.203) nor the presence of the spot sign (172.2±27.6 versus 171.8±31.6 mm Hg;
P
=0.959).

Conclusions—

Prehospital SBP is correlated with SBP on admission and independently associated with ICH volume on admission. These findings support the rationale of testing whether prehospital initiation of BP-lowering attenuates ICH expansion.