bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline
Authors: Siqueira Rafaela , Colombo Rafael , Conzatti Adriana , de Castro Alexandre Luz , Carraro Cristina Campos , Tavares Angela Maria Vicente , Fernandes Tânia Regina Gattelli , Araujo Alex Sander da Rosa , Belló-Klein Adriane
Published: August 2017

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg−1i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor β (ER-β). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.
The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cells
Authors: Chen Min , Ren Lina , Meng Yanyan , Shi Liye , Chen Ling , Yu Bo , Wu Qianqian , Qi Guoxian
Published: August 2017

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0–200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubule-associated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.
Sequential analysis and staging of a diethylnitrosamine-induced hepatocellular carcinoma in male Wistar albino rat model
Authors: Fathy Abdallah H. , Bashandy Mohamed A. , Bashandy Samir A.E. , Mansour Ahmed M. , Elsadek Bakheet
Published: August 2017

Hepatocellular carcinoma (HCC) is one of the most life-threatening cancers. The present study was designed to chronologically analyze the HCC chemically induced by diethylnitrosamine (DEN) in male Wistar rats during a 27-week period. DEN was given to rats in drinking water (100 mg/L) to induce HCC. In the present study, the DEN-administered groups recorded dramatic results in the tumor markers, oxidative stress, lipid profile, liver function, and hematological parameters at all intervals when compared with their corresponding values in the control groups. In addition, the morphometric analysis of livers of the DEN-administered groups (from 9 to 27 weeks) showed gradual enlargement and several grayish white nodules and foci on the peripheral surface of the liver as the features of HCC. In conclusion, the present sequential model chronologically analyzes all steps of hepatocarcinogenesis and presents a new staging system for classification of HCC that may be valuable for investigating the effects of anticarcinogenic compounds at varying stages of hepatocarcinogenesis in vivo.
Comparison of alloy disorder scatterings in Ga- and N-polar AlGaN/GaN heterostructures
Authors: Kang He , Li Hui-Jie , Yang Shao-Yan , Zhang Wei , Zhu Ming , Liu Li , Li Nan
Published: August 2017

The two-dimensional electron gas (2DEG) mobilities limited by alloy disorder (AD) scattering in both Ga- and N-polar AlGaN/GaN heterostructures are investigated. It was found that the AD scattering limited electron mobility in N-polar heterostructures is on the order of 103–104 cm2/Vs, which is comparable to the optical phonon scattering at room-temperature. In comparison, the AD scattering in Ga-polar samples is much less important. Moreover, the electron mobility decreases with the 2DEG density in the Ga-polar device but shows a reverse trend in the N-polar counterpart. This is found to be caused by the rather different electric field distributions in Ga- and N-polar AlGaN/GaN heterostructures. In addition, we find that an AlN interlayer can effectively reduce the alloy scattering, mainly due to the large band offset between AlN and GaN. The calculated mobilities have been compared with the experiment results and good agreements are found. We believe that our results are important for the design of AlGaN/GaN heterostructure-based devices, especially the N-polar ones.
Sex Determination in the Mammalian Germline
Authors: Spiller Cassy , Koopman Peter , Bowles Josephine
Published: August 2017

Sexual reproduction crucially depends on the production of sperm in males and oocytes in females. Both types of gamete arise from the same precursor, the germ cells. We review the events that characterize the development of germ cells during fetal life as they commit to, and prepare for, oogenesis or spermatogenesis. In females, fetal germ cells enter meiosis, whereas in males they delay meiosis and instead lose pluripotency, activate an irreversible program of prospermatogonial differentiation, and temporarily cease dividing. Both pathways involve sex-specific molecular signals from the somatic cells of the developing gonads and a suite of intrinsic receptors, signal transducers, transcription factors, RNA stability factors, and epigenetic modulators that act in complex, interconnected positive and negative regulatory networks. Understanding these networks is important in the contexts of the etiology, diagnosis, and treatment of infertility and gonadal cancers, and in efforts to augment human and animal fertility using stem cell approaches.
Ecological Stoichiometry of Ocean Plankton
Authors: Moreno Allison R. , Martiny Adam C.
Published: August 2017

Marine plankton elemental stoichiometric ratios can deviate from the Redfield ratio (106C:16N:1P); here, we examine physiological and biogeochemical mechanisms that lead to the observed variation across lineages, regions, and seasons. Many models of ecological stoichiometry blend together acclimative and adaptive responses to environmental conditions. These two pathways can have unique molecular mechanisms and stoichiometric outcomes, and we attempt to disentangle the two processes. We find that interactions between environmental conditions and cellular growth are key to understanding stoichiometric regulation, but the growth rates of most marine plankton populations are poorly constrained. We propose that specific physiological mechanisms have a strong impact on plankton and community stoichiometry in nutrient-rich environments, whereas biogeochemical interactions are important for the stoichiometry of the oligotrophic gyres. Finally, we outline key areas with missing information that is needed to advance understanding of the present and future ecological stoichiometry of ocean plankton.
Extracellular vesicles as immune mediators in response to kidney injury
Authors: Feigerlová Eva , Battaglia-Hsu Shyue-Fang , Hauet Thierry , Guéant Jean-Louis
Published: August 2017

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.
Improved methods for acrylic-free implants in nonhuman primates for neuroscience research
Authors: Overton Jacqueline A. , Cooke Dylan F. , Goldring Adam B. , Lucero Steven A. , Weatherford Conor , Recanzone Gregg H.
Published: August 2017

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal’s tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant.

NEW & NOTEWORTHY Cranial implants are often necessary for performing neurophysiology research with nonhuman primates. We present methods for using three-dimensional printed monkey skulls to form and fabricate acrylic-free implants preoperatively to decrease surgery times and the risk of complications and increase the functional life of the implant. We focused on reducing costs, creating a feasible timeline, and ensuring compatibility with existing laboratory systems. We discuss the importance of using more biocompatible materials and enhancing osseointegration.
GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the suprachiasmatic nucleus neurons
Authors: Moldavan Michael , Cravetchi Olga , Allen Charles N.
Published: August 2017

GABA is a principal neurotransmitter in the hypothalamic suprachiasmatic nucleus (SCN) that contributes to intercellular communication between individual circadian oscillators within the SCN network and the stability and precision of the circadian rhythms. GABA transporters (GAT) regulate the extracellular GABA concentration and modulate GABAA receptor (GABAAR)-mediated currents. GABA transport inhibitors were applied to study how GABAAR-mediated currents depend on the expression and function of GAT. Nipecotic acid inhibits GABA transport and induced an inward tonic current in concentration-dependent manner during whole cell patch-clamp recordings from SCN neurons. Application of either the selective GABA transporter 1 (GAT1) inhibitors NNC-711 or SKF-89976A, or the GABA transporter 3 (GAT3) inhibitor SNAP-5114, produced only small changes of the baseline current. Coapplication of GAT1 and GAT3 inhibitors induced a significant GABAAR-mediated tonic current that was blocked by gabazine. GAT inhibitors decreased the amplitude and decay time constant and increased the rise time of spontaneous GABAAR-mediated postsynaptic currents. However, inhibition of GAT did not alter the expression of either GAT1 or GAT3 in the hypothalamus. Thus GAT1 and GAT3 functionally complement each other to regulate the extracellular GABA concentration and GABAAR-mediated synaptic and tonic currents in the SCN. Coapplication of SKF-89976A and SNAP-5114 (50 µM each) significantly reduced the circadian period of Per1 expression in the SCN by 1.4 h. Our studies demonstrate that GAT are important regulators of GABAAR-mediated currents and the circadian clock in the SCN.

NEW & NOTEWORTHY In the suprachiasmatic nucleus (SCN), the GABA transporters GAT1 and GAT3 are expressed in astrocytes. Inhibition of these GABA transporters increased a tonic GABA current and reduced the circadian period of Per1 expression in SCN neurons. GAT1 and GAT3 showed functional cooperativity: inhibition of one GAT increased the activity but not the expression of the other. Our data demonstrate that GABA transporters are important regulators of GABAA receptor-mediated currents and the circadian clock.
The neural code for tactile roughness in the somatosensory nerves
Authors: Lieber Justin D. , Xia Xinyue , Weber Alison I. , Bensmaia Sliman J.
Published: August 2017

Roughness is the most salient perceptual dimension of surface texture but has no well-defined physical basis. We seek to determine the neural determinants of tactile roughness in the somatosensory nerves. Specifically, we record the patterns of activation evoked in tactile nerve fibers of anesthetized Rhesus macaques to a large and diverse set of natural textures and assess what aspect of these patterns of activation can account for psychophysical judgments of roughness, obtained from human observers. We show that perceived roughness is determined by the variation in the population response, weighted by fiber type. That is, a surface will feel rough to the extent that the activity varies across nerve fibers and varies across time within nerve fibers. We show that this variation-based neural code can account not only for magnitude estimates of roughness but also for roughness discrimination performance.

NEW & NOTEWORTHY Our sense of touch endows us with an exquisite sensitivity to the microstructure of surfaces, the most salient aspect of which is roughness. We analyze the responses evoked in tactile fibers of monkeys by natural textures and compare them to judgments of roughness obtained for the same textures from human observers. We then describe how texture signals from three populations of nerve fibers are integrated to culminate in a percept of roughness.
Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes
Authors: Kreitzer Matthew A. , Swygart David , Osborn Meredith , Skinner Blair , Heer Chad , Kaufman Ryan , Williams Bethany , Shepherd Lexi , Caringal Hannah , Gongwer Michael , Tchernookova Boriana K. , Malchow Robert P.
Published: August 2017

Self-referencing H+-selective electrodes were used to measure extracellular H+ fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H+-selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H+ flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H+ flux. Barium at 6 mM also increased H+ flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 μM DIDS, 300 μM SITS, and 30 μM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 μM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H+ fluxes, and removal of the end foot region further decreased the H+ flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H+-selective electrodes can be used to monitor H+ fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell.

NEW & NOTEWORTHY The present study uses self-referencing H+-selective electrodes for the first time to measure H+ fluxes from Müller (glial) cells isolated from tiger salamander retina. These studies demonstrate bicarbonate transport as a potent regulator of extracellular levels of acidity around Müller cells and point toward a need for further studies aimed at addressing how such glial cell pH regulatory mechanisms may shape neuronal signaling.
The Versatile Effects of Dihydromyricetin in Health
Authors: Li Hongliang , Li Qisheng , Liu Zhaowen , Yang Kai , Chen Zhixi , Cheng Qilai , Wu Longhuo
Published: August 2017

Dihydromyricetin is a flavonoid isolated from Ampelopsis grossedentata, which is traditionally used in China. Dihydromyricetin exhibits health‐benefiting activities with minimum adverse effects. Dihydromyricetin has been demonstrated to show antioxidative, anti‐inflammatory, anticancer, antimicrobial, cell death‐mediating, and lipid and glucose metabolism‐regulatory activities. Dihydromyricetin may scavenge ROS to protect against oxidative stress or potentiate ROS generation to counteract cancer cells selectively without any effects on normal cells. However, the low bioavailability of dihydromyricetin limits its potential applications. Recent research has gained positive and promising data. This review will discuss the versatile effects and clinical prospective of dihydromyricetin.
Computation of Rayleigh Damping Coefficients for the Seismic Analysis of a Hydro-Powerhouse
Authors: Song Zhiqiang , Su Chenhui
Published: August 2017

The mass and stiffness of the upper and lower structures of a powerhouse are different. As such, the first two vibration modes mostly indicate the dynamic characteristics of the upper structure, and the precise seismic response of a powerhouse is difficult to obtain on the basis of Rayleigh damping coefficients acquired using the fundamental frequencies of this structure. The damping ratio of each mode is relatively accurate when the least square method is used, but the accuracy of the damping ratios that contribute substantially to seismic responses is hardly ensured. The error of dynamic responses may even be amplified. In this study, modes that greatly influence these responses are found on the basis of mode participation mass, and Rayleigh damping coefficients are obtained. Seismic response distortion attributed to large differences in Rayleigh damping coefficients because of improper modal selection is avoided by using the proposed method, which is also simpler and more accurate than the least square method. Numerical experiments show that the damping matrix determined by using the Rayleigh damping coefficients identified by our method is closer to the actual value and the seismic response of the powerhouse is more reasonable than that revealed through the least square method.
Design and Nonlinear Control of a 2-DOF Flexible Parallel Humanoid Arm Joint Robot
Authors: Jiang Leijie , Gao Bingtuan , Zhu Zhenyu
Published: August 2017

The paper focuses on the design and nonlinear control of the humanoid wrist/shoulder joint based on the cable-driven parallel mechanism which can realize roll and pitch movement. In view of the existence of the flexible parts in the mechanism, it is necessary to solve the vibration control of the flexible wrist/shoulder joint. In this paper, a cable-driven parallel robot platform is developed for the experiment study of the humanoid wrist/shoulder joint. And the dynamic model of the mechanism is formulated by using the coupling theory of the flexible body’s large global motion and small flexible deformation. Based on derived dynamics, antivibration control of the joint robot is studied with a nonlinear control method. Finally, simulations and experiments were performed to validate the feasibility of the developed parallel robot prototype and the proposed control scheme.
High-Dose Ifosfamide Chemotherapy in a Series of Patients Affected by Myxoid Liposarcoma
Authors: Colia Vittoria , Fumagalli Elena , Provenzano Salvatore , Bertulli Rossella , Stacchiotti Silvia , Morosi Carlo , Collini Paola , Gronchi Alessandro , Casali Paolo G. , Sanfilippo Roberta
Published: August 2017

Background. To report on the activity of high-dose prolonged-infusion ifosfamide (HDIFX) chemotherapy in a retrospective series of patients affected by myxoid liposarcoma treated at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. Patients and Methods. Patients with an advanced myxoid liposarcoma treated with HDIFX (14 g/sqm, i.v., prolonged infusion of 14 days every 28 days) as a single agent between May 2002 and April 2017 were retrospectively reviewed. All pathologic diagnoses were centrally reviewed and molecularly confirmed. Response was evaluated by RECIST, and survival functions were computed by the Kaplan-Meier method. Results. Eleven patients with advanced myxoid liposarcoma were treated with HDIFX (male/female = 9/2, median age 33 years, range 31–75). Among these, 1/11 received HDIFX in first line, 5/11 in second line, 3/11 in third line, and 2/11 in fourth line for a median course number of 3 (range 2–7). No RECIST objective responses were observed. Overall median progression-free survival was 1,9 months. Median overall survival was 37 months. At a median follow-up of 115 months, 1 patient is alive. Conclusions. In this series of patients affected by advanced myxoid liposarcoma, chemotherapy with HDIFX was essentially inactive.
Antiobesity Activities of Methanolic Extracts of Amaranthus dubius, Cucurbita pepo, and Vigna unguiculata in Progesterone‐Induced Obese Mice
Authors: Nderitu Kathryn Wanjiku , Mwenda Njagi Shadrack , Macharia Ndegwa John , Barasa Stephen Super , Ngugi Mathew Piero
Published: August 2017

Amaranthus dubius, Vigna unguiculata, and Cucurbita pepo are traditionally used to manage obesity in Kenya but lack scientific validation to support their use. The aim of this study was to determine the antiobesity activity of methanolic leaf extracts of these plants in progesterone‐induced obese mice. The activity of the methanolic leaf extracts was orally bioscreened in progesterone‐induced obese mice at 200 mg/kg/bw and 400 mg/kg/bw. Body mass index was calculated once per week for four weeks and blood samples were obtained at the end of the experiment for lipid profile analysis. Antiobesity activities of the extracts were compared with the controls. Leaf extracts of A. dubius, C. pepo, and V. unguiculata, at dose concentrations of 200 mg/kgbw and 400 mg/kgbw, showed significant effects on body mass index (p < 0.05). There was no significant difference between the three extracts on lipid parameter profiles (p > 0.05). The present study showed high food intake in the negative control group as compared with normal control, positive control, and treatment groups. These extracts contained various phytochemicals such as saponins, flavonoids, alkaloids, and steroids and therefore validate use of aforementioned plants in the suppression of obesity and their use for management of obesity is recommended.
Antiamylase, Anticholinesterases, Antiglycation, and Glycation Reversing Potential of Bark and Leaf of Ceylon Cinnamon (Cinnamomum zeylanicum Blume) In Vitro
Authors: Arachchige Sirimal Premakumara Galbada , Abeysekera Walimuni Prabhashini Kaushalya Mendis , Ratnasooriya Wanigasekera Daya
Published: August 2017

Ethanol (95%) and dichloromethane : methanol (DCM : M, 1 : 1 v/v) bark extracts (BEs) and leaf extracts (LEs) of authenticated Ceylon cinnamon (CC) were studied for antiamylase, antiglucosidase, anticholinesterases, and antiglycation and glycation reversing potential in bovine serum albumin‐ (BSA‐) glucose and BSA‐methylglyoxal models in vitro. Further, total proanthocyanidins (TP) were quantified. Results showed significant differences (p < 0.05) between bark and leaf extracts for the studied biological activities (except antiglucosidase) and TP. BEs showed significantly high (p < 0.05) activities for antiamylase (IC50: 214 ± 2–215 ± 10 μg/mL), antibutyrylcholinesterase (IC50: 26.62 ± 1.66–36.09 ± 0.83 μg/mL), and glycation reversing in BSA‐glucose model (EC50: 94.33 ± 1.81–107.16 ± 3.95 μg/mL) compared to LEs. In contrast, glycation reversing in BSA‐methylglyoxal (EC50: ethanol: 122.15 ± 6.01 μg/mL) and antiglycation in both BSA‐glucose (IC50: ethanol: 15.22 ± 0.47 μg/mL) and BSA‐methylglyoxal models (IC50: DCM : M: 278.29 ± 8.55 μg/mL) were significantly high (p < 0.05) in leaf. Compared to the reference drugs used some of the biological activities were significantly (p < 0.05) high (BEs: BChE inhibition and ethanol leaf: BSA‐glucose mediated antiglycation), some were comparable (BEs: BSA‐glucose mediated antiglycation), and some were moderate (BEs and LEs: antiamylase, AChE inhibition, and BSA‐MGO mediated antiglycation; DCM : M leaf: BSA‐glucose mediated antiglycation). TP were significantly high (p < 0.05) in BEs compared to LEs (BEs and LEs: 1097.90 ± 73.01–1381.53 ± 45.93 and 309.52 ± 2.81–434.24 ± 14.12 mg cyanidin equivalents/g extract, resp.). In conclusion, both bark and leaf of CC possess antidiabetic properties and thus may be useful in managing diabetes and its complications.
Urban Dog Parks as Sources of Canine Parasites: Contamination Rates and Pet Owner Behaviours in Lisbon, Portugal
Authors: Ferreira Ana , Alho Ana Margarida , Otero David , Gomes Lídia , Nijsse Rolf , Overgaauw Paul A. M. , Madeira de Carvalho Luís
Published: August 2017

Dog parks represent a recent trend in western countries, enabling owners to spend quality time with their pets in a controlled environment. Despite their growing popularity, few studies have been performed to date on these parks to investigate dog intestinal parasitic infections and soil contamination. The present study examined 369 faecal and 18 soil samples collected from 3 dog parks in Greater Lisbon, Portugal. Additionally, 102 interviews were performed with dog owners to assess dog-walking behaviours and parasite risk. In total, 33% of the faecal dog samples were infected with at least one parasitic agent: hookworms (16.5%), Cryptosporidium spp. (11.9%), Giardia spp. (11.4%), Toxascaris leonina (1.1%), Cystoisospora spp. (1.1%), Toxocara spp. (0.5%), and Sarcocystis sp. (0.3%). The soil of all the parks was contaminated with hookworm eggs. This is the first study performed in a European urban area to assess canine faecal contamination and parasitic agents in dog parks. Our results highlight the potential of these parks as a source of transmission for canine parasites, including some with zoonotic potential. Public awareness and effective preventive measures should be promoted to minimise the health-risk impact to both animals and humans, under the scope of environmental and public health.
Fractional‐Order Model of Two‐Prey One‐Predator System
Authors: Elettreby Mohammed Fathy , Al-Raezah Ahlam Abdullah , Nabil Tamer
Published: August 2017

We propose a fractional‐order model of the interaction within two‐prey and one‐predator system. We prove the existence and the uniqueness of the solutions of this model. We investigate in detail the local asymptotic stability of the equilibrium solutions of this model. Also, we illustrate the analytical results by some numerical simulations. Finally, we give an example of an equilibrium solution that is centre for the integer order system, while it is locally asymptotically stable for its fractional‐order counterpart.
Short Stature Homeobox-Containing Haploinsufficiency in Seven Siblings with Short Stature
Authors: Sandberg Elizabeth S. , Calikoglu Ali S. , Loechner Karen J. , Snyder Lydia L.
Published: August 2017

Deficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2–15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of −2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.
PLA-Based Hybrid and Composite Electrospun Fibrous Scaffolds as Potential Materials for Tissue Engineering
Authors: Magiera Anna , Markowski Jarosław , Menaszek Elzbieta , Pilch Jan , Blazewicz Stanislaw
Published: August 2017

The aim of the study was to manufacture poly(lactic acid)- (PLA-) based nanofibrous nonwovens that were modified using two types of modifiers, namely, gelatin- (GEL-) based nanofibres and carbon nanotubes (CNT). Hybrid nonwovens consisting of PLA and GEL nanofibres (PLA/GEL), as well as CNT-modified PLA nanofibres with GEL nanofibres (PLA + CNT/GEL), in the form of mats, were manufactured using concurrent-electrospinning technique (co-ES). The ability of such hybrid structures as potential scaffolds for tissue engineering was studied. Both types of hybrid samples and one-component PLA and CNTs-modified PLA mats were investigated using scanning electron microscopy (SEM), water contact angle measurements, and biological and mechanical tests. The morphology, microstructure, and selected properties of the materials were analyzed. Biocompatibility and bioactivity in contact with normal human osteoblasts (NHOst) were studied. The coelectrospun PLA and GEL nanofibres retained their structures in hybrid samples. Both types of hybrid nonwovens were not cytotoxic and showed better osteoinductivity in comparison to scaffolds made from pure PLA. These samples also showed significantly reduced hydrophobicity compared to one-component PLA nonwovens. The CNT-contained PLA nanofibres improved mechanical properties of hybrid samples and such a 3D system appears to be interesting for potential application as a tissue engineering scaffold.
Non-Hodgkin and Hodgkin Lymphomas Select for Overexpression of BCLW
Authors: Adams Clare M. , Mitra Ramkrishna , Gong Jerald Z. , Eischen Christine M.
Published: August 2017

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an antiapoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other antiapoptotic BCL2 family members in six different B-cell lymphomas.

Experimental Design: We performed a large-scale gene expression analysis of datasets comprising approximately 2,300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as indolent and aggressive lymphomas. Data were validated experimentally with qRT-PCR and IHC.

Results: We report BCLW is significantly overexpressed in aggressive and indolent lymphomas, including DLBCL, Burkitt, follicular, mantle cell, marginal zone, and Hodgkin lymphomas. Notably, BCLW was preferentially overexpressed over that of BCL2 and negatively correlated with BCL2 in specific lymphomas. Unexpectedly, BCLW was overexpressed as frequently as BCL2 in follicular lymphoma. Evaluation of all five antiapoptotic BCL2 family members in six types of B-cell lymphoma revealed that BCL2, BCLW, and BCLX were consistently overexpressed, whereas MCL1 and A1 were not. In addition, individual lymphomas frequently overexpressed more than one antiapoptotic BCL2 family member.

Conclusions: Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other antiapoptotic BCL2 family members. Our results suggest BCLW may be equally as important in lymphomagenesis as BCL2 and that targeting BCLW in lymphomas should be considered. Clin Cancer Res; 23(22); 7119–29. ©2017 AACR.
Nonampullary Duodenal Adenomas Rarely Recur after Complete Endoscopic Resection: A Swiss Experience Including a Literature Review
Authors: Valli Piero V. , Mertens Joachim C. , Sonnenberg Amnon , Bauerfeind Peter
Published: August 2017

Introduction: Duodenal polyps and especially duodenal adenomas are a rare and mostly coincidental finding in patients undergoing upper gastrointestinal endoscopy. Due to their malignant potential, duodenal adenomas should be removed upon diagnosis. So far, the limited available data on the performance of endoscopic polypectomy show conflicting results with regard to adverse events and the adenoma recurrence rate. Patients and Methods: After summarizing the currently available data, we retrospectively analyzed all patients undergoing endoscopic resection of nonampullary duodenal adenomas (NAD) at our institution between 2006 and 2016. Results: A total of 78 patients underwent endoscopic polypectomy for NAD adenoma. End-of-treatment success with complete resection requiring a mean of 1.2 interventions was achieved in 91% (n = 71). Procedural hemorrhage occurred in 12.8% (n = 10), whereas delayed bleeding was noted in 9% (n = 7). Duodenal perforation was registered and successfully treated in 2 cases (2.6%). No adenoma recurrence was noted following primary complete adenoma resection after a mean follow-up time of 33 months. Acute post-polypectomy bleeding was statistically significantly associated with large polyp size (p = 0.003) and lack of endoscopic prophylaxis (p = 0.0008). Delayed post-polypectomy bleeding showed a trend in the occurrence of large polyps (p = 0.064), and was statistically significantly associated with familial cancer syndrome (p = 0.019) and advanced histopathology (p = 0.013). Conclusion: Our data suggest that endoscopic polypectomy of NAD is well feasible with high success rates. Procedural and delayed hemorrhage seems to be the primary issue rather than adenoma recurrence. We therefore advocate referral of patients with large NAD to experienced centers for endoscopic resection.
Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis
Authors: Kalousová Marta , Dusilová-Sulková Sylvie , Kuběna Aleš A. , Zakiyanov Oskar , Levová Kateřina , Bocková Markéta , Gedeonová Erika , Song Xue Chadtová , Ermini Maria Laura , Špringer Tomáš , Homola Jiří , Tesař Vladimír , Zima Tomáš
Published: August 2017

Background: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. Methods: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. Results: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6-10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients when tested alone. There was a significant interaction between PAPP-A and PAPP-A2 on the mortality due to infection of HD patients (p=0.008). If PAPP-A was below median, mortality due to infection was significantly higher for patients with PAPP-A2 values above median than for patients with low PAPP-A2 levels (p=0.011). Conclusion: PAPP-A2 is increased in HD patients and interacts with PAPP-A on patients´ prognosis.
N-Terminal Prosomatostatin and Risk of Vascular Dementia
Authors: Holm Hannes , Nägga Katarina , Nilsson Erik D. , Ricci Fabrizio , Cinosi Eduardo , Melander Olle , Hansson Oskar , Bachus Erasmus , Magnusson Martin , Fedorowski Artur
Published: August 2017

Background: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults. Methods: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke. Results: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values. Conclusions: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.
Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke
Authors: Guo Dong , Ma Ji , Yan Lei , Li Tengfei , Li Zhiguo , Han Xinwei , Shui Shaofeng
Published: August 2017

Background/Aims: LncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be highly expressed in an in vitro mimic of ischemic stroke conditions. However, the exact biological role of MALAT1 and its underlying mechanism in ischemic stroke remain to be elucidated. Methods: The roles of MALAT1 and miR-30a on cell death and infarct volume and autophagy were evaluated in experimental ischemic stroke. The relationships between miR-30a and MALAT1, Beclin1 were confirmed by luciferase reporter assay. The autophagy inhibitor 3-methyadenine (3-MA) was used to examine the impact of autophagy on ischemic injury. Results: We found that MALAT1, along with the levels of conversion from autophagy-related protein microtubule-associated protein light chain 3-I (LC3-I) to LC3-phosphatidylethanolamine conjugate (LC3-II), as well as Beclin1 were up-regulated and miR-30a was down-regulated in cerebral cortex neurons after oxygen-glucose deprivation (OGD) and mouse brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Down-regulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo. Furthermore, MALAT1 may serve as a molecular sponge for miR-30a and negatively regulate its expression. In addition, MALAT1 overturned the inhibitory effect of miR-30a on ischemic injury and autophagy in vitro and in vivo, which might be involved in the derepression of Beclin1, a direct target of miR-30a. Mechanistic analyses further revealed that autophagy inhibitor 3-methyadenine (3-MA) markedly suppressed OGD-induced neuronal cell death and MCAO-induced ischemic brain infarction. Conclusion: Taken together, our study first revealed that down-regulation of MALAT1 attenuated neuronal cell death through suppressing Beclin1-dependent autophagy by regulating miR-30a expression in cerebral ischemic stroke. Besides, our study demonstrated a novel lncRNA-miRNA-mRNA regulatory network that is MALAT1-miR-30a-Beclin1 in ischemic stroke, contributing to a better understanding the pathogenesis and progression of ischemic stroke.
Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury
Authors: Tan Xuexian , Zheng Xiaohe , Huang Zena , Lin Jiaqiong , Xie Chuli , Lin Yan
Published: August 2017

Background: Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI. Methods: We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells. Results: Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression. Conclusion: S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target.
The Nrf2/HO-1 Pathway Mediates the Antagonist Effect of L-Arginine On Renal Ischemia/Reperfusion Injury in Rats
Authors: Tong Fei , Zhou Xinmei
Published: August 2017

Background/Aims: Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced oxidative stress is involved in the development of acute renal injury, which can be reversed by supplementation with L-arginine, a precursor of nitric oxide (NO). This study was conducted to evaluate alterations in the expression of transcription factors [nuclear factor kappa B (NF-κB), nuclear factor-E2-related factor-2 (Nrf2), and heme oxygenase 1 (HO-1)] and heat shock protein 70 (HSP70) in the kidney of I/R-induced injury rats. Methods: Sprague-Dawley (SD) rats were subjected to bilateral renal ischemia for 45 min followed by reperfusion for 24 h. Group 1, Sham; group 2, I/R; group 3, L-arginine; and group 4, L-arginine+zinc protoporphyrin (ZnPP). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum nitric oxide (NO), histic malondialdehyde (MDA) and reactive oxygen species (ROS) and superoxide dismutase (SOD) activity were determined, and the expression levels of Nrf2, HO-1, NF-κB, and HSP70 were evaluated. Results: The treatment of rats with L-arginine produced a significant reduction in the levels of BUN, Scr, MDA and a significant enhancement in the level of NO and in the activity of SOD compared to renal I/R groups. The expression levels of Nrf2, HO-1, and HSP70 were strongly increased, and the expression of NF-κB and production of ROS were significantly decreased in the L-arginine group compared to that of the I/R group. ZnPP increased renal damage and displayed effects opposite to those of L-arginine. Conclusion: These findings suggested that L-arginine/NO reduces renal dysfunction associated with I/R of the kidney and may act as a trigger to regulate the NF-κB, HSP70 and Nrf2/HO-1 signaling cascades.
mPGES-1-Derived PGE2 Contributes to Indoxyl Sulfate-Induced Mesangial Cell Proliferation
Authors: Li Shuzhen , Sun Zhenzhen , Ding Guixia , Gong Wei , Yu Jing , Xia Weiwei , Huang Songming , Zhang Aihua , Zhang Yue , Jia Zhanjun
Published: August 2017

Background/Aims: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. Methods: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins. In another experimental setting, PGE2 was applied to the MCs to examine its direct effect on MC proliferation, as well as the regulation of prostaglandin E receptors (EPs) by qRT-PCR. Results: With the administration of IS, mPGES-1(not mPGES-2 and cytosolic PGES) was significantly upregulated at both protein and mRNA levels in line with a promoted MC proliferation. Interestingly, silencing mPGES-1 reduced cell number in S and G2 phases and blocked the upregulation of cyclin A2 and cyclin D1 in parallel with blunted PGE2 release after IS treatment, indicating that mPGES-1-derived PGE2 could contribute to MC proliferation. Furthermore, we confirmed that exogenous PGE2 could directly trigger the proliferative response in MCs. Lastly, we observed a selective upregulation of EP2 after PGE2 treatment and enhanced phosphorylation of NF-κB following IS administration in MCs, suggesting the potential involvements of EP2 and NF-κB in this pathological process. Conclusion: mPGES-1-derived PGE2 contributed to IS-induced mesangial cell proliferation.