bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Renal Electrolyte Transport by WNK and SPAK-OSR1 Kinases
Authors: Hadchouel Juliette , Ellison David H. , Gamba Gerardo
Published: February 2016

The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. WNKs regulate the activity of the Na+:Cl− cotransporter (NCC), the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), and other transport pathways. Interestingly, the modulation of NCC occurs via the phosphorylation by WNKs of other serine-threonine kinases known as SPAK-OSR1. In contrast, the process of regulating the channels is independent of SPAK-OSR1. We present a review of the remarkable advances in this area in the past 10 years.
Nuclear factor-κB regulates the expression of multiple genes encoding liver transport proteins
Authors: Balasubramaniyan Natarajan , Ananthanarayanan Meenakshisundaram , Suchy Frederick J.
Published: February 2016

In this study we identified the mechanisms underlying the inhibitory effects of NF-κB on the expression of genes encoding multiple liver transport proteins. Well-conserved NF-κB binding sites were found in the promoters of farnesoid X receptor (FXR)-target genes. An electromobility shift assay (EMSA) demonstrated the specific interaction between the NF-κB p65 protein and a 32P-labeled BSEP NF-κB response element (NF-κBE). Chromatin immunoprecipitation (ChIP) analysis confirmed binding of NF-κB p65 to the BSEP locus but not the FXRE in vitro. NF-κB p65 overexpression in Huh-7 cells markedly repressed FXR/RXR transactivation of the BSEP, ABCG5/G8, MRP2, and FXR promoters, which was totally reversed by expression of the IκBα super-repressor. NF-κB interacted directly with FXR on coimmunoprecipitation, suggesting another level for the inhibitory effects of NF-κB on FXR-target genes. In vivo ChIP analysis with liver nuclei obtained from mice after 3 days of common bile duct ligation (BDL) or 6 h post-lipopolysaccharide (LPS) injection showed a markedly increased recruitment of NF-κB p65 to the Bsep promoter compared with controls. There was also increased recruitment of the corepressor silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and histone deacetylase (HDAC)3 and HDAC2 to the NF-κB sites. We also found that NF-κB p65 was recruited to NF-κB binding sites in the promoters of organic solute transporter, OSTα and OSTβ, and unexpectedly activated rather than repressed gene expression. In mouse liver after BDL NF-κB recruitment to Ostα and Ostβ promoters was associated with increased binding of the potent coactivator cAMP response element binding protein (CREB)-binding protein (CBP)/p300 to the NF-κBE and depletion of CBP/p300 at the FXR element. Overall, these studies demonstrate a novel role for NF-κB in adaptation to obstructive and LPS-induced cholestasis acting through recruitment to specific NF-κB binding sites in the promoters of FXR-target genes and possibly through direct interaction with FXR.
Roux-en-Y gastric bypass in rats progressively decreases the proportion of fat calories selected from a palatable cafeteria diet
Authors: Mathes Clare M. , Letourneau Chanel , Blonde Ginger D. , le Roux Carel W. , Spector Alan C.
Published: February 2016

Roux-en-Y gastric bypass surgery (RYGB) decreases caloric intake in both human patients and rodent models. In long-term intake tests, rats decrease their preference for fat and/or sugar after RYGB, and patients may have similar changes in food selection. Here we evaluated the impact of RYGB on intake during a “cafeteria”-style presentation of foods to assess if rats would lower the percentage of calories taken from fat and/or sugar after RYGB in a more complex dietary context. Male Sprague-Dawley rats that underwent either RYGB or sham surgery (Sham) were presurgically and postsurgically given 8-days free access to four semisolid foods representative of different fat and sugar levels along with standard chow and water. Compared with Sham rats, RYGB rats took proportionally fewer calories from fat and more calories from carbohydrates; the latter was not attributable to an increase in sugar intake. The proportion of calories taken from protein after RYGB also increased slightly. Importantly, these postsurgical macronutrient caloric intake changes in the RYGB rats were progressive, making it unlikely that the surgery had an immediate impact on the hedonic evaluation of the foods and strongly suggesting that learning is influencing the food choices. Indeed, despite these dietary shifts, RYGB, as well as Sham, rats continued to select the majority of their calories from the high-fat/high-sugar option. Apparently after RYGB, rats can progressively regulate their intake and selection of complex foods to achieve a seemingly healthier macronutrient dietary composition.
Ablation of eNOS does not promote adipose tissue inflammation
Authors: Jurrissen Thomas J. , Sheldon Ryan D. , Gastecki Michelle L. , Woodford Makenzie L. , Zidon Terese M. , Rector R. Scott , Vieira-Potter Victoria J. , Padilla Jaume
Published: February 2016

Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, 10-wk-old C57BL6 wild-type and endothelial nitric oxide synthase (eNOS) knockout male mice were randomized to either a control diet (10% kcal from fat) or a Western diet (44.9% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 wk ( n = 7 or 8/group). In wild-type mice, Western diet-induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNF-α, and CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs, and Mac-2 protein), as well as reduced markers of mitochondrial content (e.g., OXPHOS complex I and IV protein). Unexpectedly, these effects of Western diet on visceral white AT were not accompanied by decreases in eNOS phosphorylation at Ser-1177 or increases in eNOS phosphorylation at Thr-495. Also counter to expectations, eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared with wild-type mice. Collectively, these findings do not support the hypothesis that reduced NO production from eNOS contributes to obesity-related AT inflammation.
Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways
Authors: Zhuo Jia L. , Kobori H. , Li Xiao C. , Satou R. , Katsurada A. , Navar L. Gabriel
Published: February 2016

Long-term angiotensin II (ANG II) infusion significantly increases ANG II levels in the kidney through two major mechanisms: AT1receptor-mediated augmentation of angiotensinogen (AGT) expression and uptake of circulating ANG II by the proximal tubules. However, it is not known whether intracellular ANG II stimulates AGT expression in the proximal tubule. In the present study, we overexpressed an intracellular cyan fluorescent ANG II fusion protein (Ad-sglt2-ECFP/ANG II) selectively in the proximal tubule of rats and mice using the sodium and glucose cotransporter 2 (sglt2) promoter. AGT mRNA and protein expression in the renal cortex and 24-h urinary AGT excretion were determined 4 wk following overexpression of ECFP/ANG II in the proximal tubule. Systolic blood pressure was significantly increased with a small antinatriuretic effect in rats and mice with proximal tubule-selective expression of ECFP/ANG II ( P < 0.01). AGT mRNA and protein expression in the cortex were increased by >1.5-fold and 61 ± 16% ( P < 0.05), whereas urinary AGT excretion was increased from 48.7 ± 5.7 ( n = 13) to 102 ± 13.5 ( n = 13) ng/24 h ( P < 0.05). However, plasma AGT, renin activity, and ANG II levels remained unaltered by ECFP/ANG II. The increased AGT mRNA and protein expressions in the cortex by ECFP/ANG II were blocked in AT1a-knockout (KO) mice. Studies in cultured mouse proximal tubule cells demonstrated involvement of AT1areceptor/MAP kinases/NF-кB signaling pathways. These results indicate that intracellular ANG II stimulates AGT expression in the proximal tubules, leading to increased AGT formation and secretion into the tubular fluid, which contributes to ANG II-dependent hypertension.
FGF23 from bench to bedside
Authors: Kovesdy Csaba P. , Quarles L. Darryl
Published: February 2016

There is a strong association between elevated circulating fibroblast growth factor-23 (FGF23) levels and adverse outcomes in patients with chronic kidney disease (CKD) of all stages. Initially discovered as a regulator of phosphate and vitamin D homeostasis, FGF23 has now been implicated in several pathophysiological mechanisms that may negatively impact the cardiovascular and renal systems. FGF23 is purported to have direct (off-target) effects in the myocardium, as well as canonical effects on FGF receptor/α-klotho receptor complexes in the kidney to activate the renin-angiotensin-aldosterone system, modulate soluble α-klotho levels, and increase sodium retention, to cause left ventricular hypertrophy (LVH). Conversely, FGF23 could be an innocent bystander produced in response to chronic inflammation or other processes associated with CKD that cause LVH and adverse cardiovascular outcomes. Further exploration of these complex mechanisms is needed before modulation of FGF23 can become a legitimate clinical target in CKD.
Increased ventilatory variability and complexity in patients with hyperventilation disorder
Authors: Bokov Plamen , Fiamma Marie-Noëlle , Chevalier-Bidaud Brigitte , Chenivesse Cécile , Straus Christian , Similowski Thomas , Delclaux Christophe
Published: February 2016

It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28–48], P = 0.020; slope: −6.63 [−7.65; −5.36] vs. −3.88 [−5.91; −2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039–0.221] vs. 0.044 [0.012–0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 − degree 5: Rho = −0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions.
Whisker-related afferents in superior colliculus
Authors: Castro-Alamancos Manuel A. , Favero Morgana
Published: February 2016

Rodents use their whiskers to explore the environment, and the superior colliculus is part of the neural circuits that process this sensorimotor information. Cells in the intermediate layers of the superior colliculus integrate trigeminotectal afferents from trigeminal complex and corticotectal afferents from barrel cortex. Using histological methods in mice, we found that trigeminotectal and corticotectal synapses overlap somewhat as they innervate the lower and upper portions of the intermediate granular layer, respectively. Using electrophysiological recordings and optogenetics in anesthetized mice in vivo, we showed that, similar to rats, whisker deflections produce two successive responses that are driven by trigeminotectal and corticotectal afferents. We then employed in vivo and slice experiments to characterize the response properties of these afferents. In vivo, corticotectal responses triggered by electrical stimulation of the barrel cortex evoke activity in the superior colliculus that increases with stimulus intensity and depresses with increasing frequency. In slices from adult mice, optogenetic activation of channelrhodopsin-expressing trigeminotectal and corticotectal fibers revealed that cells in the intermediate layers receive more efficacious trigeminotectal, than corticotectal, synaptic inputs. Moreover, the efficacy of trigeminotectal inputs depresses more strongly with increasing frequency than that of corticotectal inputs. The intermediate layers of superior colliculus appear to be tuned to process strong but infrequent trigeminal inputs and weak but more persistent cortical inputs, which explains features of sensory responsiveness, such as the robust rapid sensory adaptation of whisker responses in the superior colliculus.
Sensorimotor recalibration during split-belt walking: task-specific and multisensory?
Authors: Hoogkamer Wouter , O'Brien Megan K.
Published: February 2016

Motor adaptations not only recalibrate movement execution but also can lead to altered movement perception in multiple sensory domains. Vazquez, Statton, Busgang, and Bastian ( J Neurophysiol 114: 3255–3267, 2015) recently showed that split-belt walking affects perception of leg speed during walking, but not perceptions of leg position during standing and walking or perception of contact force during stepping. Considering their findings within the broader scope of sensorimotor recalibration in other tasks, we suggest that sensorimotor recalibrations are task specific and can be multisensory.
Effects of transcranial direct current stimulation of primary somatosensory cortex on vibrotactile detection and discrimination
Authors: Labbé Sara , Meftah El-Mehdi , Chapman C. Elaine
Published: February 2016

Anodal transcranial direct current stimulation (a-tDCS) of primary somatosensory cortex (S1) has been shown to enhance tactile spatial acuity, but there is little information as to the underlying neuronal mechanisms. We examined vibrotactile perception on the distal phalanx of the middle finger before, during, and after contralateral S1 tDCS [a-, cathodal (c)-, and sham (s)-tDCS]. The experiments tested our shift-gain hypothesis, which predicted that a-tDCS would decrease vibrotactile detection and discrimination thresholds (leftward shift of the stimulus-response function with increased gain/slope) relative to s-tDCS, whereas c-tDCS would have the opposite effects (relative to s-tDCS). The results showed that weak a-tDCS (1 mA, 20 min) led to a reduction in both vibrotactile detection and discrimination thresholds to 73–76% of baseline during the application of the stimulation in subjects categorized as responders. These effects persisted after the end of a-tDCS but were absent 30 min later. Most, but not all, subjects showed a decrease in threshold (8/12 for detection; 9/12 for discrimination). Intersubject variability was explained by a ceiling effect in the discrimination task. c-tDCS had no significant effect on either detection or discrimination threshold. Taken together, our results supported our shift-gain hypothesis for a-tDCS but not c-tDCS.
Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal)
Authors: Schmid Anne-Christine , Chien Jui-Hong , Greenspan Joel D. , Garonzik Ira , Weiss Nirit , Ohara Shinji , Lenz Frederick Arthur
Published: February 2016

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.
Visual ecology and potassium conductances of insect photoreceptors
Authors: Frolov Roman , Immonen Esa-Ville , Weckström Matti
Published: February 2016

Voltage-activated potassium channels (Kv channels) in the microvillar photoreceptors of arthropods are responsible for repolarization and regulation of photoreceptor signaling bandwidth. On the basis of analyzing Kv channels in dipteran flies, it was suggested that diurnal, rapidly flying insects predominantly express sustained K+conductances, whereas crepuscular and nocturnally active animals exhibit strongly inactivating Kv conductances. The latter was suggested to function for minimizing cellular energy consumption. In this study we further explore the evolutionary adaptations of the photoreceptor channelome to visual ecology and behavior by comparing K+conductances in 15 phylogenetically diverse insects, using patch-clamp recordings from dissociated ommatidia. We show that rapid diurnal flyers such as the blowfly ( Calliphora vicina) and the honeybee ( Apis mellifera) express relatively large noninactivating Kv conductances, conforming to the earlier hypothesis in Diptera. Nocturnal and/or slow-moving species do not in general exhibit stronger Kv conductance inactivation in the physiological membrane voltage range, but the photoreceptors in species that are known to rely more on vision behaviorally had higher densities of sustained Kv conductances than photoreceptors of less visually guided species. No statistically significant trends related to visual performance could be identified for the rapidly inactivating Kv conductances. Counterintuitively, strong negative correlations were observed between photoreceptor capacitance and specific membrane conductance for both sustained and inactivating fractions of Kv conductance, suggesting insignificant evolutionary pressure to offset negative effects of high capacitance on membrane filtering with increased conductance.
Long-latency reflexes of elbow and shoulder muscles suggest reciprocal excitation of flexors, reciprocal excitation of extensors, and reciprocal inhibition between flexors and extensors
Authors: Kurtzer Isaac , Meriggi Jenna , Parikh Nidhi , Saad Kenneth
Published: February 2016

Postural corrections of the upper limb are required in tasks ranging from handling an umbrella in the changing wind to securing a wriggling baby. One complication in this process is the mechanical interaction between the different segments of the arm where torque applied at one joint induces motion at multiple joints. Previous studies have shown the long-latency reflexes of shoulder muscles (50–100 ms after a limb perturbation) account for these mechanical interactions by integrating information about motion of both the shoulder and elbow. It is less clear whether long-latency reflexes of elbow muscles exhibit a similar capability and what is the relation between the responses of shoulder and elbow muscles. The present study utilized joint-based loads tailored to the subjects' arm dynamics to induce well-controlled displacements of their shoulder and elbow. Our results demonstrate that the long-latency reflexes of shoulder and elbow muscles integrate motion from both joints: the shoulder and elbow flexors respond to extension at both joints, whereas the shoulder and elbow extensors respond to flexion at both joints. This general pattern accounts for the inherent flexion-extension coupling of the two joints arising from the arm's intersegmental dynamics and is consistent with spindle-based reciprocal excitation of shoulder and elbow flexors, reciprocal excitation of shoulder and elbow extensors, and across-joint inhibition between the flexors and extensors.
Neural control of visual search by frontal eye field: chronometry of neural events and race model processes
Authors: Nelson Matthew J. , Murthy Aditya , Schall Jeffrey D.
Published: February 2016

We investigated the chronometry of neural processes in frontal eye fields of macaques performing double-step saccade visual search in which a conspicuous target changes location in the array on a random fraction of trials. Durations of computational processes producing a saccade to original and final target locations (GO1 and GO2, respectively) are derived from response times (RT) on different types of trials. In these data, GO2 tended to be faster than GO1, demonstrating that inhibition of the initial saccade did not delay production of the compensated saccade. Here, we measured the dynamics of visual, visuomovement, and movement neuron activity in relation to these processes by examining trials when neurons instantiated either process. First, we verified that saccades were initiated when the discharge rate of movement neurons reached a threshold that was invariant across RT and trial type. Second, the time when visual and visuomovement neurons selected the target and when movement neuron activity began to accumulate were not significantly different across trial type. Third, the interval from the beginning of accumulation to threshold of movement-related activity was significantly shorter when instantiating the GO2 relative to the GO1 process. Differences observed between monkeys are discussed. Fourth, random variation of RT was accounted for to some extent by random variation in both the onset and duration of selective activity of each neuron type but mostly by variation of movement neuron accumulation duration. These findings offer new insights into the sources of control of target selection and saccade production in dynamic environments.
Intercellular Adhesion Molecule and Endogenous NOS Inhibitor: Asymmetric Dimethylarginine in Pregnant Women with Gestational Diabetes Mellitus
Authors: Poniedziałek-Czajkowska Elżbieta , Mierzyński Radzisław , Szymula Dariusz , Leszczyńska-Gorzelak Bożena , Oleszczuk Jan
Published: February 2016

Objective. The aim of the study was to evaluate the concentrations of soluble intercellular adhesion molecule-1 (s-ICAM-1) and endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), as markers of endothelium dysfunction in patients with gestational diabetes mellitus (GDM).Patients and Methods. The levels of s-ICAM-1 and ADMA were analysed in the group of 56 patients with GDM and compared to 25 healthy pregnant women. The concentrations of s-ICAM-1 and ADMA were measured in serum using ELISA tests.Results. The groups did not differ by baseline descriptors: age (30.75±6.32versus28.50±4.95years, NS) and gestational age (28.96±2.85versus29.12±2.96hbd, NS). The patients with GDM were more obese (BMI27.93±7.02versus22.34±4.21 kg/m2,p=0.032) and had higher concentration of C-reactive protein (6.46±6.03versus3.18±3.83 mg/L,p=0.029). In the GDM group the level of ADMA was lower (0.38±0.17versus0.60±0.28 μmol/L,p=0.001) and the level of s-ICAM-1 was significantly higher (289.95±118.12 versus232.56±43.31 ng/mL,p=0.036) compared to controls.Conclusions. The pregnant women with GDM are characterized by higher concentration of s-ICAM-1 that reflects the activation and dysfunction of the endothelial cells. The decreased ADMA level in GDM patients seems to be preventive in the limitation of NO synthesis caused by the impaired insulin action and the endothelial dysfunction.
Protective Sliding Carbon-Based Nanolayers Prepared by Argon or Nitrogen Ion-Beam Assisted Deposition on Ti6Al4V Alloy
Authors: Vlcak Petr , Jirka Ivan
Published: February 2016

The microstructure and the surface properties of samples coated by carbon-based nanolayer were investigated in an effort to increase the surface hardness and reduce the coefficient of friction of the Ti6Al4V alloy. Protective carbon-based nanolayers were fabricated by argon or nitrogen ion-beam assisted deposition at ion energy of 700 eV on Ti6Al4V substrates. The Raman spectra indicated that nanolayers had a diamond-like carbon character with sp2rich bonds. The TiC and TiN compounds formed in the surface area were detected by X-ray diffraction. Nanoscratch tests showed increased adhesion of a carbon-based nanolayer deposited with ion assistance in comparison with a carbon nanolayer deposited without ion assistance. The results showed that argon ion assistance leads to greater nanohardness than a sample coated by a carbon-based nanolayer with nitrogen ion assistance. A more than twofold increase in nanohardness and a more than fivefold decrease in the coefficient of friction were obtained for samples coated by a carbon-based nanolayer with ion assistance, in comparison with the reference sample.
Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice
Authors: Steimle Alex , Frick Julia-Stefanie
Published: February 2016

How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.
Prediction of the PSNR Quality of Decoded Images in Fractal Image Coding
Authors: Wang Qiang , Bi Sheng
Published: February 2016

With many observations, we find that there exists a logarithmic relationship between the average collage error (ACER) and the PSNR quality of decoded images. By making use of ACER in the encoding process, the curve fitting result can help us to predict the PSNR quality of decoded images. Then, in order to reduce the computational complexity further, an accelerated version of the prediction method is proposed. Firstly, a low limit of percentage of accumulated collage error (LLPACE) is proposed to evaluate the actual percentage of accumulated collage error (APACE). If LLPACE reaches a large value, such as 90%, the corresponding APACE can be proved to be limited in a small range (90%–100%) and the APACE can be estimated approximately. Thus, the remaining range blocks can be neglected and the corresponding computations can be saved. With the approximated APACE and the logarithmic relationship, the quality of decoded images can be predicted directly. Experiments show that, for four fractal coding methods, the quality of decoded images can be predicted accurately. Furthermore, the accelerated prediction method can provide competitive performance and reduce about one-third of total computations in the encoding process. Finally, the application of the proposed method is also discussed and analyzed.
Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management
Authors: Govind Babu K. , Lokesh K. N. , Suresh Babu M. C. , Bhat Gita R.
Published: February 2016

Background.Acute promyelocytic leukemia is characterized by t(15;17). This leads to the formation of PML/RARαwhich blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA), a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA.Case Report.We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease.Conclusions.We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.
A Simplified Method for the Aspiration of Bone Marrow from Patients Undergoing Hip and Knee Joint Replacement for Isolating Mesenchymal Stem Cells andIn VitroChondrogenesis
Authors: Juneja Subhash C. , Viswanathan Sowmya , Ganguly Milan , Veillette Christian
Published: February 2016

The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon’s skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians.
Is It Possible to Maintain Consciousness and Spontaneous Ventilation with Chest Compression in the Early Phase of Cardiac Arrest?
Authors: Oksar Menekse , Turhanoglu Selim
Published: February 2016

Chest compression is important in cardiopulmonary resuscitation. However, life support algorithms do not specify when chest compression should be initiated in patients with persistent spontaneous normal breathing in the early phase after cardiac arrest. Here we describe the case of a 69-year-old man who underwent femoral bypass surgery and was extubated at the end of the procedure. After extubation, the patient’s breathing pattern and respiratory rate were normal. The patient subsequently developed ventricular fibrillation, evident on two monitors. Because defibrillation was ineffective, chest compression was initiated even though the patient had spontaneous normal breathing and defensive motor reflexes, which were continued throughout resuscitation. He regained consciousness and underwent tracheal extubation without neurological sequelae on postoperative day 1. This case highlights the necessity of chest compression in the early phase of cardiac arrest.
Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes
Authors: Yang Ying , Zhou Tai-Cheng , Liu Yong-Ying , Li Xiao , Wang Wen-Xue , Irwin David M. , Zhang Ya-Ping
Published: February 2016

Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in theHNF4α,GCK,HNF-1α,IPF-1,HNF1β, andNEUROD1genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulatedHNF4Aexpression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations inHNF4AandHNF1Agenes might account for this early-onset inherited type 2 diabetes.
A Game for Energy-Aware Allocation of Virtualized Network Functions
Authors: Bruschi Roberto , Carrega Alessandro , Davoli Franco
Published: February 2016

Network Functions Virtualization (NFV) is a network architecture concept where network functionality is virtualized and separated into multiple building blocks that may connect or be chained together to implement the required services. The main advantages consist of an increase in network flexibility and scalability. Indeed, each part of the service chain can be allocated and reallocated at runtime depending on demand. In this paper, we present and evaluate an energy-aware Game-Theory-based solution for resource allocation of Virtualized Network Functions (VNFs) within NFV environments. We consider each VNF as a player of the problem that competes for the physical network node capacity pool, seeking the minimization of individual cost functions. The physical network nodes dynamically adjust their processing capacity according to the incoming workload, by means of an Adaptive Rate (AR) strategy that aims at minimizing the product of energy consumption and processing delay. On the basis of the result of the nodes’ AR strategy, the VNFs’ resource sharing costs assume a polynomial form in the workflows, which admits a unique Nash Equilibrium (NE). We examine the effect of different (unconstrained and constrained) forms of the nodes’ optimization problem on the equilibrium and compare the power consumption and delay achieved with energy-aware and non-energy-aware strategy profiles.
Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function
Authors: Wang Yi , Liang Xinying , Chen Yaqi , Zhao Xiaoping
Published: February 2016

Sirtuin type 1 (SIRT1) belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1‐activation effects by liquid chromatography‐mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert‐butyl hydroperoxide (t‐BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn‐SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t‐BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress‐induced mitochondrial damage in cardiomyocytes through activation of SIRT1.
Structural, Electrical, Dielectric, and Magnetic Properties of Cd2+ Substituted Nickel Ferrite Nanoparticles
Authors: Devmunde B. H. , Raut A. V. , Birajdar S. D. , Shukla S. J. , Shengule D. R. , Jadhav K. M.
Published: February 2016

In the present investigation structural, electric, magnetic, and frequency dependent dielectric properties of Ni1-xCdxFe2O4 ferrite nanoparticles (NPs) (where x=0.2, 0.4, 0.6, and 0.8) prepared by sol-gel autocombustion method were studied. The crystallite size (t) (46.89~58.40 nm) was estimated from X-ray diffraction data with the postconfirmation of single phase spinel structure. Spherical shaped, fused grain nature with intergranular diffusion in Ni1-xCdxFe2O4 NPs was observed in scanning electron micrographs. The value of loss tangent (tan⁡δ) decreases exponentially with an increasing frequency indicating normal Maxwell-Wagner type dielectric dispersion due to interfacial polarization. Decreasing values of Curie temperature (TC) from 860°C to 566°C with increasing Cd2+ content x in Ni1-xCdxFe2O4 NPs were determined from AC-Susceptibility. Activation energy ΔE ranges within 0.03~0.15 eV. Decreasing magnetic saturation Ms, coercivity Hc, and magneton number nB values show the effect on nonmagnetic Cd2+ ions over magnetic Ni2+ and Fe ions.
Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes
Authors: Jossen Valentin , Schirmer Cedric , Mostafa Sindi Dolman , Eibl Regine , Kraume Matthias , Pörtner Ralf , Eibl Dieter
Published: February 2016

The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale‐up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier‐based stirred bioreactors have demonstrated the successful use of Computational Fluid Dynamics (CFD) and suspension criteria (NS1u, NS1) for rapidly scaling up hMSC expansions from mL‐ to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier‐cell‐aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth. The dependence of microcarrier‐cell‐aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d32) versus time. Cultivation at the suspension criteria provided d32 values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 106 cells mL−1 hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterion NS1u was investigated for scaling up microcarrier‐based processes in wave‐mixed bioreactors for the first time.
Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells
Authors: He Yunfan , Lu Feng
Published: February 2016

Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large‐scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells.
Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers
Authors: Richard Egbe Edmund , Augusta Chinyere Nsonwu-Anyanwu , Jeremaiah Offor Sunday , Opara Usoro Chinyere Adanna , Henrieta Etukudo Maise , Ifunanya Egbe Deborah
Published: February 2016

Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed.Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function{aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)}, and serum elements{lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)}were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation atp=0.05.Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p<0.05). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p<0.05). Negative correlation was observed between duration of exposure and PEFR (r=-0.416,p=0.016) in cement workers.Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate.
Tumor Mesenchymal Stem‐Like Cell as a Prognostic Marker in Primary Glioblastoma
Authors: Yoon Seon-Jin , Shim Jin-Kyoung , Chang Jong Hee , Moon Ju Hyung , Roh Tae-Hoon , Sung Kyoung Su , Lee Ji-Hyun , Kim Eui-Hyun , Kim Sun Ho , Hong Yong-Kil , Lee Su-Jae , Huh Yong-Min , Kang Seok-Gu
Published: February 2016

The isolation from brain tumors of tumor mesenchymal stem‐like cells (tMSLCs) suggests that these cells play a role in creating a microenvironment for tumor initiation and progression. The clinical characteristics of patients with primary glioblastoma (pGBM) positive for tMSLCs have not been determined. This study analyzed samples from 82 patients with pGBM who had undergone tumor removal, pathological diagnosis, and isolation of tMSLC from April 2009 to October 2014. Survival, extent of resection, molecular markers, and tMSLC culture results were statistically evaluated. Median overall survival was 18.6 months, 15.0 months in tMSLC‐positive patients and 29.5 months in tMSLC‐negative patients (P = 0.014). Multivariate cox regression model showed isolation of tMSLC (OR = 2.5, 95% CI = 1.1~5.6, P = 0.021) showed poor outcome while larger extent of resection (OR = 0.5, 95% CI = 0.2~0.8, P = 0.011) has association with better outcome. The presence of tMSLCs isolated from the specimen of pGBM is associated with the survival of patient.
Spurious Hyperchloremia and Negative Anion Gap in a Child with Refractory Epilepsy
Authors: Chegondi Madhuradhar , Totapally Balagangadhar R.
Published: February 2016

We report a case with spurious hyperchloremia with negative anion gap in a child who was taking potassium bromide for refractory epilepsy. Blood chemistry showed a high chloride level (171 mEq/L) and a negative anion gap (−52 mEq/L). Plasma chloride concentration is measured by an ion-selective electrode method; however the presence of other anions like bromide and iodides can interfere with chloride level and largely overestimates the chloride concentration. Thus hyperchloremia with a negative anion gap is a clue to the diagnosis of halides like bromide and iodide ingestion.
The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats
Authors: Turgut Nergiz H. , Kara Haki , Elagoz Sahende , Deveci Koksal , Gungor Huseyin , Arslanbas Emre
Published: February 2016

The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-αand IL-1βlevels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson’s trichrome, and 0.1% toluidine blue. TNF-α, IL-1β, and MDA levels and hydroxyproline content significantly increased (p<0.01) and GPx and SOD activities significantly decreased in bleomycin group (p<0.01). Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-αand IL-1βactivity, hydroxyproline content, and MDA level (p<0.01) and increased GPx and SOD activities (p<0.05). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.
The Content and Bioavailability of Mineral Nutrients of Selected Wild and Traditional Edible Plants as Affected by Household Preparation Methods Practiced by Local Community in Benishangul Gumuz Regional State, Ethiopia
Authors: Hailu Andinet Abera , Addis Getachew
Published: February 2016

Edible parts of some wild and traditional vegetables used by the Gumuz community, namely,Portulaca quadrifida,Dioscorea abyssinica,Abelmoschus esculentus, andOxytenanthera abyssinica, were evaluated for their minerals composition and bioavailability. Mineral elements, namely, Ca, Fe, Zn, and Cu, were analyzed using Shimadzu atomic absorption spectrophotometer. Effects of household processing practices on the levels of mineral elements were evaluated and the bioavailability was predicted using antinutrient-mineral molar ratios. Fe, Zn, Ca, Cu, P, Na, and K level in raw edible portions ranged in (0.64 ± 0.02–27.0 ± 6.24), (0.46 ± 0.02–0.85 ± 0.02), (24.49 ± 1.2–131.7 ± 8.3), (0.11 ± 0.01–0.46 ± 0.04), (39.13 ± 0.34–57.27 ± 0.94), (7.34 ± 0.42–20.42 ± 1.31), and (184.4 ± 1.31–816.3 ± 11.731) mg/100 g FW, respectively. Although statistically significant losses in minerals as a result of household preparation practices were observed, the amount of nutrients retained could be valuable especially in communities that have limited alternative sources of these micronutrients. The predicted minerals’ bioavailability shows adequacy in terms of calcium and zinc but not iron.