bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen and testosterone in concert with EFNB3 regulate vascular smooth muscle cell contractility and blood pressure
Authors: Wang Yujia , Wu Zenghui , Thorin Eric , Tremblay Johanne , Lavoie Julie L. , Luo Hongyu , Peng Junzheng , Qi Shijie , Wu Tao , Chen Fei , Shen Jianzhong , Hu Shenjiang , Wu Jiangping
Published: April 2016

EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions, although their function in blood pressure (BP) control has not been studied in detail. In the present study, we report that Efnb3 gene knockout (KO) led to increased BP in female but not male mice. Vascular smooth muscle cells (VSMCs) were target cells for EFNB3 function in BP regulation. The deletion of EFNB3 augmented contractility of VSMCs from female but not male KO mice, compared with their wild-type (WT) counterparts. Estrogen augmented VSMC contractility while testosterone reduced it in the absence of EFNB3, although these sex hormones had no effect on the contractility of VSMCs from WT mice. The effect of estrogen on KO VSMC contractility was via a nongenomic pathway involving GPER, while that of testosterone was likely via a genomic pathway, according to VSMC contractility assays and GPER knockdown assays. The sex hormone-dependent contraction phenotypes in KO VSMCs were reflected in BP in vivo. Ovariectomy rendered female KO mice normotensive. At the molecular level, EFNB3 KO in VSMCs resulted in reduced myosin light chain kinase phosphorylation, an event enhancing sensitivity to Ca2+flux in VSMCs. Our investigation has revealed previously unknown EFNB3 functions in BP regulation and show that EFNB3 might be a hypertension risk gene in certain individuals.
Loss of knee extensor torque complexity during fatiguing isometric muscle contractions occurs exclusively above the critical torque
Authors: Pethick Jamie , Winter Samantha L. , Burnley Mark
Published: April 2016

The complexity of knee extensor torque time series decreases during fatiguing isometric muscle contractions. We hypothesized that because of peripheral fatigue, this loss of torque complexity would occur exclusively during contractions above the critical torque (CT). Nine healthy participants performed isometric knee extension exercise (6 s of contraction, 4 s of rest) on six occasions for 30 min or to task failure, whichever occurred sooner. Four trials were performed above CT (trials S1–S4, S1 being the lowest intensity), and two were performed below CT (at 50% and 90% of CT). Global, central, and peripheral fatigue were quantified using maximal voluntary contractions (MVCs) with femoral nerve stimulation. The complexity of torque output was determined using approximate entropy (ApEn) and the detrended fluctuation analysis-α scaling exponent (DFA-α). The MVC torque was reduced in trials below CT [by 19 ± 4% (means ± SE) in 90%CT], but complexity did not decrease [ApEn for 90%CT: from 0.82 ± 0.03 to 0.75 ± 0.06, 95% paired-samples confidence intervals (CIs), 95% CI = −0.23, 0.10; DFA-α from 1.36 ± 0.01 to 1.32 ± 0.03, 95% CI −0.12, 0.04]. Above CT, substantial reductions in MVC torque occurred (of 49 ± 8% in S1), and torque complexity was reduced (ApEn for S1: from 0.67 ± 0.06 to 0.14 ± 0.01, 95% CI = −0.72, −0.33; DFA-α from 1.38 ± 0.03 to 1.58 ± 0.01, 95% CI 0.12, 0.29). Thus, in these experiments, the fatigue-induced loss of torque complexity occurred exclusively during contractions performed above the CT.
Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation
Authors: Hasdemir Burcu , Mhaske Pallavi , Paruthiyil Sreenivasan , Garnett Elizabeth A. , Heyman Melvin B. , Matloubian Mehrdad , Bhargava Aditi
Published: April 2016

We investigated whether corticotropin-releasing factor receptor 2 (CRF2) and its high-affinity agonist urocortin 1 (Ucn1) mediate sex-specific signaling and immune responses. Intrarectal trinitrobenzene sulfonic acid was used to induce experimental colitis in wild-type, CRF2knockout (CRF2KO), and heterozygous (CRF2Ht) mice of both sexes. Changes in plasma extravasation, organ weight, survival, immune cell numbers, inflammatory cytokines, and the MAPK signaling pathway were assessed. Stored intestinal biopsies from patients with Crohn's disease (CD) and age- and sex-matched individuals without inflammatory bowel disease (IBD) were examined by immunofluorescence and confocal microscopy to characterize Ucn1 and CRF receptor expression. CRF2Ht mice of both sexes showed decreased survival during colitis compared with other genotypes. Ucn1 improved survival in male mice alone. Ucn1 restored colon length and spleen and adrenal weight and decreased colonic TNF-α, IL-6, and IL-1β levels in male CRF2Ht mice alone. CRF2Ht mice of both sexes showed decreased phosphorylation of MAPK p38 and heat shock protein 27 (Hsp27) levels. Ucn1 restored p-Hsp27 levels in male CRF2Ht mice alone. Expression of the chaperone protein Hsp90 decreased during colitis, except in male CRF2Ht mice. Taken together, our data indicate that sex shows significant interaction with genotype and Ucn1 during colitis. Human duodenal and colonic biopsies revealed that sex-specific differences exist in levels of CRF receptors and Ucn1 expression in patients with CD compared with the matched non-IBD subjects. To conclude, Ucn1 mediates sex-specific immune and cellular signaling responses via CRF2, emphasizing the need for inclusion of females in preclinical studies.
Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle
Authors: Fyfe Jackson J. , Bishop David J. , Zacharewicz Evelyn , Russell Aaron P. , Stepto Nigel K.
Published: April 2016

We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean ± SD: age, 27 ± 4 yr; V̇o2 peak,45.7 ± 9 ml·kg−1·min−1) performed three experimental trials in a randomized order: 1) RE (8 × 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 × 2 min at 120% lactate threshold (LT); HIT + RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT + RE). Vastus lateralis muscle biopsies were obtained immediately before RE, either without (REST) or with (POST) preceding endurance exercise and +1 h (RE + 1 h) and +3 h (RE + 3 h) after RE. Prior HIT and MICT similarly reduced muscle glycogen content and increased ACCSer79and p70S6KThr389phosphorylation before subsequent RE (i.e., at POST). Compared with MICT, HIT induced greater mTORSer2448and rps6Ser235/236phosphorylation at POST. RE-induced increases in p70S6K and rps6 phosphorylation were not influenced by prior HIT or MICT; however, mTOR phosphorylation was reduced at RE + 1 h for MICT + RE vs. both HIT + RE and RE. Expression of miR-133a, miR-378, and miR-486 was reduced at RE + 1 h for HIT + RE vs. both MICT + RE and RE. Postexercise mTORC1 signaling following RE is therefore not compromised by prior HIT or MICT, and concurrent exercise incorporating HIT, but not MICT, reduces postexercise expression of miRNAs implicated in skeletal muscle adaptation to RE.
Hindbrain cytoglucopenia-induced increases in systemic blood glucose levels by 2-deoxyglucose depend on intact astrocytes and adenosine release
Authors: Rogers Richard C. , Ritter Sue , Hermann Gerlinda E.
Published: April 2016

The hindbrain contains critical neurocircuitry responsible for generating defensive physiological responses to hypoglycemia. This counter-regulatory response (CRR) is evoked by local hindbrain cytoglucopenia that causes an autonomically mediated increase in blood glucose, feeding behavior, and accelerated digestion; that is, actions that restore glucose homeostasis. Recent reports suggest that CRR may be initially triggered by astrocytes in the hindbrain. The present studies in thiobutabarbital-anesthetized rats show that exposure of the fourth ventricle (4V) to 2-deoxyglucose (2DG; 15 μmol) produced a 35% increase in circulating glucose relative to baseline levels. While the 4V application of the astrocytic signal blocker, fluorocitrate (FC; 5 nmol), alone, had no effect on blood glucose levels, 2DG-induced increases in glucose were blocked by 4V FC. The 4V effect of 2DG to increase glycemia was also blocked by the pretreatment with caffeine (nonselective adenosine antagonist) or a potent adenosine A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine; DPCPX) but not the NMDA antagonist (MK-801). These results suggest that CNS detection of glucopenia is mediated by astrocytes and that astrocytic release of adenosine that occurs after hypoglycemia may cause the activation of downstream neural circuits that drive CRR.
Cardiovascular function, compliance, and connective tissue remodeling in the turtle,Trachemys scripta, following thermal acclimation
Authors: Keen Adam N. , Shiels Holly A. , Crossley Dane A.
Published: April 2016

Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in the slider turtle.
Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term
Authors: Yates Dustin T. , Cadaret Caitlin N. , Beede Kristin A. , Riley Hannah E. , Macko Antoni R. , Anderson Miranda J. , Camacho Leticia E. , Limesand Sean W.
Published: April 2016

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller ( P < 0.05) than controls and exhibited hypoxemia and hypoglycemia, which contributed to 6.9-fold greater ( P < 0.05) plasma norepinephrine and ∼53% lower ( P < 0.05) plasma insulin concentrations. IUGR semitendinosus muscles contained less ( P < 0.05) myosin heavy chain-I protein (MyHC-I) and proportionally fewer ( P < 0.05) Type I and Type I/IIa fibers than controls, but MyHC-II protein concentrations, Type II fibers, and Type IIx fibers were not different. IUGR biceps femoris muscles exhibited similar albeit less dramatic differences in fiber type proportions. Type I and IIa fibers are more responsive to adrenergic and insulin regulation than Type IIx and may be more profoundly impaired by the high catecholamines and low insulin in our IUGR fetuses, leading to their proportional reduction. In both muscles, fibers of each type were uniformly smaller ( P < 0.05) in IUGR fetuses than controls, which indicates that fiber hypertrophy is not dependent on type but rather on other factors such as myoblast differentiation or protein synthesis. Together, our findings show that IUGR fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance.
Partial podocyte replenishment in experimental FSGS derives from nonpodocyte sources
Authors: Kaverina Natalya V. , Eng Diana G. , Schneider Remington R. S. , Pippin Jeffrey W. , Shankland Stuart J.
Published: April 2016

The current studies used genetic fate mapping to prove that adult podocytes can be partially replenished following depletion. Inducible NPHS2-rtTA/tetO-Cre/RS-ZsGreen-R reporter mice were generated to permanently label podocytes with the ZsGreen reporter. Experimental focal segmental glomerulosclerosis (FSGS) was induced with a cytotoxic podocyte antibody. On FSGS day 7, immunostaining for the podocyte markers p57, synaptopodin, and podocin were markedly decreased by 44%, and this was accompanied by a decrease in ZsGreen fluorescence. The nuclear stain DAPI was absent in segments of reduced ZsGreen and podocyte marker staining, which is consistent with podocyte depletion. Staining for p57, synaptopodin, podocin, and DAPI increased at FSGS day 28 and was augmented by the ACE inhibitor enalapril, which is consistent with a partial replenishment of podocytes. In contrast, ZsGreen fluorescence did not return and remained significantly low at day 28, indicating replenishment was from a nonpodocyte origin. Despite administration of bromodeoxyuridine (BrdU) thrice weekly throughout the course of disease, BrdU staining was not detected in podocytes, which is consistent with an absence of proliferation. Although ZsGreen reporting was reduced in the tuft at FSGS day 28, labeled podocytes were detected along the Bowman's capsule in a subset of glomeruli, which is consistent with migration from the tuft. Moreover, more than half of the migrated podocytes coexpressed the parietal epithelial cell (PEC) proteins claudin-1, SSeCKS, and PAX8. These results show that although podocytes can be partially replenished following abrupt depletion, a process augmented by ACE inhibition, the source or sources are nonpodocyte in origin and are independent of proliferation. Furthermore, a subset of podocytes migrate to the Bowman's capsule and begin to coexpress PEC markers.
Impaired carotid baroreflex control of arterial blood pressure in multiple sclerosis
Authors: Huang Mu , Allen Dustin R. , Keller David M. , Fadel Paul J. , Frohman Elliot M. , Davis Scott L.
Published: April 2016

Multiple sclerosis (MS), a progressive neurological disease, can lead to impairments in the autonomic control of cardiovascular function. We tested the hypothesis that individuals with relapsing-remitting MS ( n = 10; 7 females, 3 males; 13 ± 4 yr from diagnosis) exhibit impaired carotid baroreflex control of blood pressure and heart rate compared with sex, age, and body weight-matched healthy individuals (CON: n = 10; 7 females, 3 males). At rest, 5-s trials of neck pressure (NP; +40 Torr) and neck suction (NS; −60 Torr) were applied to simulate carotid hypotension and hypertension, respectively, while mean arterial pressure (MAP; finger photoplethysmography), heart rate (HR), cardiac output (CO; Modelflow), and total vascular conductance (TVC) were continuously measured. In response to NP, there was a blunted increase in peak MAP responses (MS: 5 ± 2 mmHg) in individuals with MS compared with healthy controls (CON: 9 ± 3 mmHg; P = 0.005), whereas peak HR responses were not different between groups. At the peak MAP response to NP, individuals with MS demonstrated an attenuated decrease in TVC (MS, −10 ± 4% baseline vs. CON, −15 ± 4% baseline, P = 0.012), whereas changes in CO were similar between groups. Following NS, all cardiovascular responses (i.e., nadir MAP and HR and percent changes in CO and TVC) were not different between MS and CON groups. These data suggest that individuals with MS have impaired carotid baroreflex control of blood pressure via a blunted vascular conductance response resulting in a diminished ability to increase MAP in response to a hypotensive challenge.
Visual-vestibular processing in the human Sylvian fissure
Authors: Frank Sebastian M. , Wirth Anna Maria , Greenlee Mark W.
Published: April 2016

Unlike other sensory systems, the cortical organization of the human vestibular system is not well established. A central role is assumed for the region of the posterior Sylvian fissure, close to the posterior insula. At this site, activation during vestibular stimulation has been observed in previous imaging studies and labeled as the parieto-insular vestibular cortex area (PIVC). However, vestibular responses are found in other parts of the Sylvian fissure as well, including a region that is referred to as the posterior insular cortex (PIC). The anatomical and functional relationship between PIC and PIVC is still poorly understood, because both areas have never been compared in the same participants. Therefore, to better understand the apparently more complex organization of vestibular cortex in the Sylvian fissure, we employed caloric and visual object motion stimuli during functional magnetic resonance imaging and compared location and function of PIVC and PIC in the same participants. Both regions responded to caloric vestibular stimulation, but only the activation pattern in right PIVC reliably represented the direction of the caloric stimulus. Conversely, activity in PIVC was suppressed during stimulation with visual object motion, whereas PIC showed activation. Area PIC is located at a more posterior site in the Sylvian fissure than PIVC. Our results suggest that PIVC and PIC should be considered separate areas in the vestibular Sylvian network, both in terms of location and function.
Integration of sensory, spinal, and volitional descending inputs in regulation of human locomotion
Authors: Gerasimenko Yury , Gad Parag , Sayenko Dimitry , McKinney Zach , Gorodnichev Ruslan , Puhov Aleksandr , Moshonkina Tatiana , Savochin Aleksandr , Selionov Victor , Shigueva Tatiana , Tomilovskaya Elena , Kozlovskaya Inessa , Edgerton V. Reggie
Published: April 2016

We reported previously that both transcutaneous electrical spinal cord stimulation and direct pressure stimulation of the plantar surfaces of the feet can elicit rhythmic involuntary step-like movements in noninjured subjects with their legs in a gravity-neutral apparatus. The present experiments investigated the convergence of spinal and plantar pressure stimulation and voluntary effort in the activation of locomotor movements in uninjured subjects under full body weight support in a vertical position. For all conditions, leg movements were analyzed using electromyographic (EMG) recordings and optical motion capture of joint kinematics. Spinal cord stimulation elicited rhythmic hip and knee flexion movements accompanied by EMG bursting activity in the hamstrings of 6/6 subjects. Similarly, plantar stimulation induced bursting EMG activity in the ankle flexor and extensor muscles in 5/6 subjects. Moreover, the combination of spinal and plantar stimulation exhibited a synergistic effect in all six subjects, eliciting greater motor responses than either modality alone. While the motor responses to spinal vs. plantar stimulation seems to activate distinct but overlapping spinal neural networks, when engaged simultaneously, the stepping responses were functionally complementary. As observed during induced (involuntary) stepping, the most significant modulation of voluntary stepping occurred in response to the combination of spinal and plantar stimulation. In light of the known automaticity and plasticity of spinal networks in absence of supraspinal input, these findings support the hypothesis that spinal and plantar stimulation may be effective tools for enhancing the recovery of motor control in individuals with neurological injuries and disorders.
Voltage imaging to understand connections and functions of neuronal circuits
Authors: Antic Srdjan D. , Empson Ruth M. , Knöpfel Thomas
Published: April 2016

Understanding of the cellular mechanisms underlying brain functions such as cognition and emotions requires monitoring of membrane voltage at the cellular, circuit, and system levels. Seminal voltage-sensitive dye and calcium-sensitive dye imaging studies have demonstrated parallel detection of electrical activity across populations of interconnected neurons in a variety of preparations. A game-changing advance made in recent years has been the conceptualization and development of optogenetic tools, including genetically encoded indicators of voltage (GEVIs) or calcium (GECIs) and genetically encoded light-gated ion channels (actuators, e.g., channelrhodopsin2). Compared with low-molecular-weight calcium and voltage indicators (dyes), the optogenetic imaging approaches are 1) cell type specific, 2) less invasive, 3) able to relate activity and anatomy, and 4) facilitate long-term recordings of individual cells' activities over weeks, thereby allowing direct monitoring of the emergence of learned behaviors and underlying circuit mechanisms. We highlight the potential of novel approaches based on GEVIs and compare those to calcium imaging approaches. We also discuss how novel approaches based on GEVIs (and GECIs) coupled with genetically encoded actuators will promote progress in our knowledge of brain circuits and systems.
Changes in muscle spindle firing in response to length changes of neighboring muscles
Authors: Smilde Hiltsje A. , Vincent Jake A. , Baan Guus C. , Nardelli Paul , Lodder Johannes C. , Mansvelder Huibert D. , Cope Tim C. , Maas Huub
Published: April 2016

Skeletal muscle force can be transmitted to the skeleton, not only via its tendons of origin and insertion but also through connective tissues linking the muscle belly to surrounding structures. Through such epimuscular myofascial connections, length changes of a muscle may cause length changes within an adjacent muscle and hence, affect muscle spindles. The aim of the present study was to investigate the effects of epimuscular myofascial forces on feedback from muscle spindles in triceps surae muscles of the rat. We hypothesized that within an intact muscle compartment, muscle spindles not only signal length changes of the muscle in which they are located but can also sense length changes that occur as a result of changing the length of synergistic muscles. Action potentials from single afferents were measured intra-axonally in response to ramp-hold release (RHR) stretches of an agonistic muscle at different lengths of its synergist, as well as in response to synergist RHRs. A decrease in force threshold was found for both soleus (SO) and lateral gastrocnemius afferents, along with an increase in length threshold for SO afferents. In addition, muscle spindle firing could be evoked by RHRs of the synergistic muscle. We conclude that muscle spindles not only signal length changes of the muscle in which they are located but also local length changes that occur as a result of changing the length and relative position of synergistic muscles.
Sensory reweighting dynamics following removal and addition of visual and proprioceptive cues
Authors: Assländer Lorenz , Peterka Robert J.
Published: April 2016

Removing or adding sensory cues from one sensory system during standing balance causes a change in the contribution of the remaining sensory systems, a process referred to as sensory reweighting. While reweighting changes have been described in many studies under steady-state conditions, less is known about the temporal dynamics of reweighting following sudden transitions to different sensory conditions. The present study changed sensory conditions by periodically adding or removing visual (lights On/Off) or proprioceptive cues (surface sway referencing On/Off) in 12 young, healthy subjects. Evidence for changes in sensory contributions to balance was obtained by measuring the time course of medial-lateral sway responses to a constant-amplitude 0.56-Hz sinusoidal stimulus, applied as support surface tilt (proprioceptive contribution), as visual scene tilt (visual contribution), or as binaural galvanic vestibular stimulation (vestibular contribution), and by analyzing the time course of sway variability. Sine responses and variability of body sway velocity showed significant changes following transitions and were highly correlated under steady-state conditions. A dependence of steady-state responses on upcoming transitions was observed, suggesting that knowledge of impending changes can influence sensory weighting. Dynamic changes in sway in the period immediately following sensory transitions were very inhomogeneous across sway measures and in different experimental tests. In contrast to steady-state results, sway response and variability measures were not correlated with one another in the dynamic transition period. Several factors influence sway responses following addition or removal of sensory cues, partly instigated by but also obscuring the effects of reweighting dynamics.
Synthesis, Morphology, and Optical Properties of Au/CdS Hybrid Nanocomposites Stabilized by Branched Polymer Matrices
Authors: Chumachenko V. A. , Naumenko A. P. , Yeshchenko O. A. , Kutsevol N. V. , Bondarchuk I. S.
Published: April 2016

Metal/semiconductor (Au/CdS) nanocomposites were synthesized in the solution of branched D-g-PAA polymer. TEM and DLS of Au/CdS/D-g-PAA nanocomposites revealed complicated nanocomposite structure consisting of the Au nanoparticles (NPs) of 6 nm in size surrounded by small CdS NPs with size of 3 nm. These nanocomposites formed the aggregates-clusters with average size of 50–800 nm. Absorption spectra of Au/CdS nanocomposites consist of the bands of excitons in CdS NPs and surface plasmons in Au ones. The surface plasmon band of gold NPs is red shifted and broadened in Au/CdS/D-g-PAA nanocomposites comparing to the one of Au NPs in Au/D-g-PAA proving the fact of close location of CdS and Au NPs in the synthesized Au/CdS/D-g-PAA nanocomposites. The PL spectra of Au/CdS nanocomposites originate from the radiative transitions in excitons in CdS NPs. The 4-fold increase of intensity of free exciton PL is observed for CdS NPs in Au/CdS/D-g-PAA comparing to CdS ones in CdS/D-g-PAA that is due to PL enhancement by local field of surface plasmons of Au NPs. Also, the 12-fold decrease of intensity of localized exciton PL is observed for CdS NPs in Au/CdS/D-g-PAA comparing to CdS ones in CdS/D-g-PAA. Most probably, it is due to passivation of the surface of CdS NPs carried out by the Au ones.
Unilateral Maxillary First Molar Extraction in Class II Subdivision: An Unconventional Treatment Alternative
Authors: Booij J. W. , Livas Christos
Published: April 2016

The asymmetrical intra-arch relationship in Class II subdivision malocclusion poses challenges in the treatment planning and mechanotherapy of such cases. This case report demonstrates a treatment technique engaging unilateral extraction of a maxillary first molar and Begg fixed appliances. The outcome stability and the enhancing effect on the eruption of the third molar in the extraction segment were confirmed by a 4-year follow-up examination.
Study on the Rollover Characteristic of In-Wheel-Motor-Driven Electric Vehicles Considering Road and Electromagnetic Excitation
Authors: Tan Di , Wang Haitao , Wang Qiang
Published: April 2016

For in-wheel-motor-driven electric vehicles, the motor is installed in the wheel directly. Tyre runout and uneven load can cause magnet gap deformation in the motor, which will produce electromagnetic forces that further influence the vehicle rollover characteristics. To study the rollover characteristics, a verified 16-degree-of-freedom rollover dynamic model is introduced. Next, the vehicle rollover characteristics both with and without electromagnetic force are analyzed under conditions of the Fixed Timing Fishhook steering and grade B road excitation. The results show that the electromagnetic force has a certain effect on the load transfer and can reduce the antirollover performance of the vehicle. Therefore, the effect of the electromagnetic force on the rollover characteristic should be considered in the vehicle design. To this end, extensive analysis was conducted on the effect of the road level, vehicle speed, and the road adhesion coefficient on the vehicle rollover stability. The results indicate that vehicle rollover stability worsens when the above-mentioned factors increase, the most influential factor being the road adhesion coefficient followed by vehicle speed and road level. This paper can offer certain theory basis for the design of the in-wheel-motor-driven electric vehicles.
Lycium barbarumPolysaccharide Mediated the Antidiabetic and Antinephritic Effects in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats via Regulation of NF-κB
Authors: Du Mingzhao , Hu Xinyu , Kou Ling , Zhang Baohai , Zhang Chaopu
Published: April 2016

Lycium barbarum, extensively utilized as a medicinal plant in China for years, exhibits antitumor, immunoregulative, hepatoprotective, and neuroprotective properties. The present study aims to investigate the hyperglycemic and antidiabetic nephritic effects of polysaccharide which is separated fromLycium barbarum(LBPS) in high-fat diet-streptozotocin- (STZ-) induced rat models. The reduced bodyweight and enhanced blood glucose concentration in serum were observed in diabetic rats, and they were significantly normalized to the healthy level by 100 mg/kg of metformin (Met) and LBPS at doses of 100, 250, and 500 mg/kg. LBPS inhibited albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors including IL-2, IL-6, TNF-α, IFN-α, MCP-1, and ICAM-1 compared with diabetic rats, and it indicates the protection on renal damage. Furthermore, the activities of SOD and GSH-Px in serum were enhanced strikingly by LBPS which suggests its antioxidation effects. LBPS, compared with nontreated diabetic rats, inhibited the expression of phosphor-nuclear factors kappa B (NF-κB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPS possesses antidiabetic and antinephritic effects related to NF-κB-mediated antioxidant and antiinflammatory activities.
Investigation of the Larvicidal Potential of Silver Nanoparticles againstCulex quinquefasciatus: A Case of a Ubiquitous Weed as a Useful Bioresource
Authors: Adesuji Elijah T. , Oluwaniyi Omolara O. , Adegoke Haleemat I. , Moodley Roshila , Labulo Ayomide H. , Bodede Olusola S. , Oseghale Charles O.
Published: April 2016

Biosynthesized silver nanoparticles (AgNPs) usingCassia hirsutaaqueous leaf extract were reported in this study. The synthesis was optimized by measuring various parameters such as temperature, time, volume ratio, and concentration. The surface plasmon resonance at 440 nm for 30°C and 420 nm for both 50°C and 70°C measured using the UV-Vis spectrophotometer confirmed the formation of AgNPs synthesized usingC.hirsuta(CAgNPs). The functional groups responsible for the reduction and stabilization of the NPs were identified using Fourier Transform Infrared (FTIR). The morphology, size, and elemental composition of the NPs were obtained using scanning electron microscope (SEM), transmission electron microscope (TEM), and energy dispersive X-ray spectroscopy (EDX). X-ray diffractometer was used to identify the phases and crystallinity of CAgNPs. Crystalline spherical NPs with average diameter of 6.9 ± 0.1 nm were successfully synthesized. The thermal analysis of CAgNPs was observed from DSC-TGA. The larvicidal results against the different larva instar stage ofCulex quinquefasciatusgave LC50= 4.43 ppm and LC90= 8.37 ppm. This is the first study on the synthesis of AgNPs usingC.hirsutaand its application against lymphatic filariasis vector. Hence, it is suggested that theC.hirsutasynthesized AgNPs would be environmentally benign in biological control of mosquito.
Synthesis and Characterization of Pumice-Supported nZVI for Removal of Copper from Waters
Authors: Harman Bilgehan Ilker , Genisoglu Mesut
Published: April 2016

The target of this work was to study the synthesis and characterization of pumice-supported nanoscale zero-valent iron (nZVI) and the effectiveness of nZVI coated pumice to remove copper from water. The impacts of pumice dose, pumice surface chemistry, pH, and water source on copper removal were studied. Natural pumice particles were used as granular support media and coated with nZVI. Results of nZVI coated pumice characterization showed nZVI coated successfully on pumice surface being proved with characterization methods such as SEM-EDS, XPS, and XRF. nZVI coating overwhelmed the surface chemistry properties of the underlying pumice particles. Higher surface areas and more iron content were obtained in nZVI coated pumice. nZVI coating significantly increased copper uptake compared to uncoated particles. High removal capacity has been observed for all tested pH values. Control experiments indicated that nZVI bound on pumice surfaces is stable at pH values of typical natural waters. The nZVI coated pumice was found to be effective in removing copper from waters having a wide range of specific UV absorbance (SUVA) values. Overall, the results indicated that nZVI coated pumice particles are maybe alternative adsorbents to remove copper.
Traditional Therapies Used to Manage Diabetes and Related Complications in Mauritius: A Comparative Ethnoreligious Study
Authors: Mahomoodally M. Fawzi , Mootoosamy A. , Wambugu S.
Published: April 2016

Religious communities from Mauritius still rely on traditional therapies (TT) for primary healthcare. Nonetheless, there is still a dearth of scientific information on TT used by the different religious groups to manage diabetes and related complications (DRC). This study aimed to gather ethnomedicinal knowledge on TT used by the different religious groups against DRC. Diabetic patients (n = 95) and traditional healers (n = 5) were interviewed. Fifty‐two plant species belonging to 33 families and 26 polyherbal formulations were documented to manage DRC. The most reported DRC was hypertension (n = 36). Leaves (45.2%) and juice (36%) were the most cited mode of preparation of herbal recipes. Plants which scored high relative frequency of citation were Citrus aurantifolia (0.55) and Morinda citrifolia (0.54). The cultural importance index showed that Ocimum tenuiflorum, Cardiospermum halicacabum, Camellia sinensis, and Ophiopogon japonicas were the most culturally important plants among Hindu, Muslim, Christian, and Buddhist community, respectively. Hindu and Muslim community showed the highest similarity of medicinal plants usage (Jaccard index = 95.8). Seven animal species distributed over 4 classes were recorded for the management of DRC. Plants and animals recorded as TT should be submitted to scientific studies to confirm safety and efficacy in clinical practice and to identify pharmacologically active metabolites.
Bounds on Worst-Case Deadline Failure Probabilities in Controller Area Networks
Authors: Short Michael
Published: April 2016

Industrial communication networks like the Controller Area Network (CAN) are often required to operate reliably in harsh environments which expose the communication network to random errors. Probabilistic schedulability analysis can employ rich stochastic error models to capture random error behaviors, but this is most often at the expense of increased analysis complexity. In this paper, an efficient method (of time complexityO(n log n)) to bound the message deadline failure probabilities for an industrial CAN network consisting ofnperiodic/sporadic message transmissions is proposed. The paper develops bounds for Deadline Minus Jitter Monotonic (DMJM) and Earliest Deadline First (EDF) message scheduling techniques. Both random errors and random bursts of errors can be included in the model. Stochastic simulations and a case study considering DMJM and EDF scheduling of an automotive benchmark message set provide validation of the technique and highlight its application.
Developing a Suitable Model for Water Uptake for Biodegradable Polymers Using Small Training Sets
Authors: Valenzuela Loreto M. , Knight Doyle D. , Kohn Joachim
Published: April 2016

Prediction of the dynamic properties of water uptake across polymer libraries can accelerate polymer selection for a specific application. We first built semiempirical models using Artificial Neural Networks and all water uptake data, as individual input. These models give very good correlations (R2>0.78for test set) but very low accuracy on cross-validation sets (less than 19% of experimental points within experimental error). Instead, using consolidated parameters like equilibrium water uptake a good model is obtained (R2=0.78for test set), with accurate predictions for 50% of tested polymers. The semiempirical model was applied to the 56-polymer library of L-tyrosine-derived polyarylates, identifying groups of polymers that are likely to satisfy design criteria for water uptake. This research demonstrates that a surrogate modeling effort can reduce the number of polymers that must be synthesized and characterized to identify an appropriate polymer that meets certain performance criteria.
Thoracic Paravertebral Block, Multimodal Analgesia, and Monitored Anesthesia Care for Breast Cancer Surgery in Primary Lateral Sclerosis
Authors: Dizdarevic Anis , Fernandes Anthony
Published: April 2016

Objective.Primary lateral sclerosis (PLS) is a rare idiopathic neurodegenerative disorder affecting upper motor neurons and characterized by spasticity, muscle weakness, and bulbar involvement. It can sometimes mimic early stage of more common and fatal amyotrophic lateral sclerosis (ALS). Surgical patients with a history of neurodegenerative disorders, including PLS, may be at increased risk for general anesthesia related ventilatory depression and postoperative respiratory complications, abnormal response to muscle relaxants, and sensitivity to opioids, sedatives, and local anesthetics. We present a case of a patient with PLS and recent diagnosis of breast cancer who underwent a simple mastectomy surgery uneventfully under an ultrasound guided thoracic paravertebral block, multimodal analgesia, and monitored anesthesia care. Patient reported minimal to no pain or discomfort in the postoperative period and received no opioids for pain management before being discharged home. In patients with PLS, thoracic paravertebral block and multimodal analgesia can provide reliable anesthesia and effective analgesia for breast surgery with avoidance of potential risks associated with general anesthesia, muscle paralysis, and opioid use.
A New Surgical Approach for the Treatment of Conjunctivochalasis: Reduction of the Conjunctival Fold with Bipolar Electrocautery Forceps
Authors: Arenas Eduardo , Muñoz Diana
Published: April 2016

Aim. To report a new surgical technique for the treatment of conjunctivochalasis.Methods. A new surgical technique in which specially designed bipolar electrocautery forceps facilitate the complete reduction of the conjunctival folds without creating lesions near the corneoscleral limbus was designed. A retrospective revision of the medical records of patients treated with this technique between the years 2011 and 2013 was made, and eighteen eyes of sixteen patients with conjunctivochalasis treated with this new technique were included.Results.All the eyes treated showed a significant improvement with no evidence of scar lesions after a mean follow-up time of 10 months.Conclusions. The surgical technique presented here could be a good alternative for the management of conjunctivochalasis.
The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies
Authors: Muntean Danina M. , Sturza Adrian , Dănilă Maria D. , Borza Claudia , Duicu Oana M. , Mornoș Cristian
Published: April 2016

Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST‐elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria‐derived ROS are briefly reviewed.
Febuxostat and Increased Dialysis as a Treatment for Severe Tophaceous Gout in a Hemodialysis Patient
Authors: Frassetto Lynda Ann , Gibson Suzanne
Published: April 2016

Uric acid accumulates in renal failure and is thought to be a uremic toxin—that is, higher levels of uric acid are more damaging to the kidneys. Urate crystals can precipitate in the kidney tubules, cause urate stones, and promote inflammatory changes in the renal interstitium and vascular endothelium. Uric acid is also a small non-protein-bound molecule and therefore easily dialyzable. Here, we present the case of an anuric hemodialysis patient with severe tophaceous gout who regained some renal function and whose gout burden significantly decreased resulting in marked improvement in functional status using a new gout medication, febuxostat, and increased frequency of dialysis.
Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential
Authors: George Jasmine , Ahmad Nihal
Published: April 2016

The past few decades have witnessed a furious attention of scientific community toward identifying novel molecular factors and targets that could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1–7) differ in their cellular localization and biologic functions. Among these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRT) regulate multiple cellular and physiologic processes, including cell cycle, gene expression, cell viability, stress response, metabolism, and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. Although the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer. Cancer Res; 76(9); 2500–6. ©2016 AACR.
A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2
Authors: Yang Shouhui , He Peijun , Wang Jian , Schetter Aaron , Tang Wei , Funamizu Naotake , Yanaga Katsuhiko , Uwagawa Tadashi , Satoskar Abhay R. , Gaedcke Jochen , Bernhardt Markus , Ghadimi B. Michael , Gaida Matthias M. , Bergmann Frank , Werner Jens , Ried Thomas , Hanna Nader , Alexander H. Richard , Hussain S. Perwez
Published: April 2016

Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumors in multiple cohorts of pancreatic ductal adenocarcinoma (PDAC) patients. The key genes and pathways identified were linked to patient survival and were mechanistically, functionally, and clinically characterized using cell lines, a genetically engineered mouse model, and PDAC patient cohorts. Here, we report evidence of a novel MIF-driven signaling pathway that inhibits the orphan nuclear receptor NR3C2, a previously undescribed tumor suppressor that impacts aggressiveness and survival in PDAC. Mechanistically, MIF upregulated miR-301b that targeted NR3C2 and suppressed its expression. PDAC tumors expressing high levels of MIF displayed elevated levels of miR-301b and reduced levels of NR3C2. In addition, reduced levels of NR3C2 expression correlated with poorer survival in multiple independent cohorts of PDAC patients. Functional analysis showed that NR3C2 inhibited epithelial-to-mesenchymal transition and enhanced sensitivity to the gemcitabine, a chemotherapeutic drug used in PDAC standard of care. Furthermore, genetic deletion of MIF disrupted a MIF–mir-301b–NR3C2 signaling axis, reducing metastasis and prolonging survival in a genetically engineered mouse model of PDAC. Taken together, our results offer a preclinical proof of principle for candidate therapies to target a newly described MIF–miR-301b–NR3C2 signaling axis for PDAC management. Cancer Res; 76(13); 3838–50. ©2016 AACR.
Carcinoma Cell Hyaluronan as a “Portable” Cancerized Prometastatic Microenvironment
Authors: Turley Eva A. , Wood David K. , McCarthy James B.
Published: April 2016

Hyaluronan (HA) is a structurally simple polysaccharide, but its ability to act as a template for organizing pericellular matrices and its regulated synthesis and degradation are key to initiating repair responses. Importantly, these HA functions are usurped by tumor cells to facilitate progression and metastasis. Recent advances have identified the functional complexities associated with the synthesis and degradation of HA-rich matrices. Three enzymes synthesize large HA polymers while multiple hyaluronidases or tissue free radicals degrade these into smaller bioactive fragments. A family of extracellular and cell-associated HA-binding proteins/receptors translates the bioinformation encrypted in this complex polymer mixture to activate signaling networks required for cell survival, proliferation, and migration in an actively remodeling microenvironment. Changes in HA metabolism within both the peritumor stroma and parenchyma are linked to tumor initiation, progression, and poor clinical outcome. We review evidence that metastatic tumor cells must acquire the capability to autonomously synthesize, assemble, and process their own “portable” HA-rich microenvironments to survive in the circulation, metastasize to ectopic sites, and escape therapeutic intervention. Strategies to disrupt the HA machinery of primary tumor and circulating tumor cells may enhance the effectiveness of current conventional and targeted therapies. Cancer Res; 76(9); 2507–12. ©2016 AACR.