bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells
Authors: Sundararaj Kamala , Rodgers Jessalyn I. , Marimuthu Subathra , Siskind Leah J. , Bruner Evelyn , Nowling Tamara K.
Published: January 2018

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.
Highly tamoxifen-inducible principal cell-specific Cre mice with complete fidelity in cell specificity and no leakiness
Authors: Chen Lihe , Gao Chao , Zhang Long , Zhang Ye , Chen Enuo , Zhang Wenzheng
Published: January 2018

An ideal inducible system should be cell specific and have absolutely no background recombination without induction (i.e., no leakiness), a high recombination rate after induction, and complete fidelity in cell specificity (i.e., restricted recombination exclusively in cells where the driver gene is expressed). However, such an ideal mouse model remains unavailable for collecting duct research. Here, we report a mouse model that meets these criteria. In this model, a cassette expressing ERT2CreERT2 ( ECE) is inserted at the ATG of the endogenous Aqp2 locus to disrupt Aqp2 function and to express ECE under the control of the Aqp2 promoter. The resulting allele is named Aqp2ECE. There was no indication of a significant impact of disruption of a copy of Aqp2 on renal function and blood pressure control in adult Aqp2ECE/+ heterozygotes. Without tamoxifen, Aqp2ECE did not activate a Cre-dependent red fluorescence protein (RFP) reporter in adult kidneys. A single injection of tamoxifen (2 mg) to adult mice enabled Aqp2ECE to induce robust RFP expression in the whole kidney 24 h postinjection, with the highest recombination efficiency of 95% in the inner medulla. All RFP-labeled cells expressed principal cell markers (Aqp2 and Aqp3), but not intercalated cell markers (V-ATPase B1B2, and carbonic anhydrase II). Hence, Aqp2ECE confers principal cell-specific tamoxifen-inducible recombination with absolutely no leakiness, high inducibility, and complete fidelity in cell specificity, which should be an important tool for temporospatial control of target genes in the principal cells and for Aqp2+ lineage tracing in adult mice.
Renal potassium handling in rats with subtotal nephrectomy: modeling and analysis
Authors: Layton Anita T. , Edwards Aurélie , Vallon Volker
Published: January 2018

We sought to decipher the mechanisms underlying the kidney’s response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a sham rat, an uninephrectomized (UNX) rat, and a 5/6-nephrectomized (5/6-NX) rat that also considers adaptations in glomerular filtration rate and tubular growth. Model simulations of an acute K+ load indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels, large-conductance Ca2+-activated K+ channels, and renal outer medullary K+ channels, together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a >6-fold increase in urinary K+ excretion in sham rats, which substantially exceeds the filtered K+ load. In the UNX and 5/6-NX models, the acute K+ load is predicted to increase K+ excretion, but at significantly reduced levels compared with sham. Acute K+ load is accompanied by natriuresis in sham rats. Model simulations suggest that the lesser natriuretic effect observed in the nephrectomized groups may be explained by impaired NCC downregulation in these kidneys. At a single-nephron level, a high K+ intake raises K+ secretion along the connecting tubule and reabsorption along the collecting duct in sham, and even more in UNX and 5/6-NX. However, the increased K+ secretion per tubule fails to sufficiently compensate for the reduction in nephron number, such that nephrectomized rats have an impaired ability to excrete an acute or chronic K+ load.
Renal ischemia-reperfusion injury causes hypertension and renal perfusion impairment in the CD1 mice which promotes progressive renal fibrosis
Authors: Greite Robert , Thorenz Anja , Chen Rongjun , Jang Mi-Sun , Rong Song , Brownstein Michael J. , Tewes Susanne , Wang Li , Baniassad Bita , Kirsch Torsten , Bräsen Jan Hinrich , Lichtinghagen Ralf , Meier Martin , Haller Hermann , Hueper Katja , Gueler Faikah
Published: January 2018

Renal ischemia-reperfusion injury (IRI) is a severe complication of major surgery and a risk factor for increased morbidity and mortality. Here, we investigated mechanisms that might contribute to IRI-induced progression to chronic kidney disease (CKD). Acute kidney injury (AKI) was induced by unilateral IRI for 35 min in CD1 and C57BL/6 (B6) mice. Unilateral IRI was used to overcome early mortality. Renal morphology, NGAL upregulation, and neutrophil infiltration as well as peritubular capillary density were studied by immunohistochemistry. The composition of leukocyte infiltrates in the kidney after IRI was investigated by flow cytometry. Systemic blood pressure was measured with a tail cuff, and renal perfusion was quantified by functional magnetic resonance imaging (fMRI). Mesangial matrix expansion was assessed by silver staining. Following IRI, CD1 and B6 mice developed similar morphological signs of AKI and increases in NGAL expression, but neutrophil infiltration was greater in CD1 than B6 mice. IRI induced an increase in systemic blood pressure of 20 mmHg in CD1, but not in B6 mice; and CD1 mice also had a greater loss of renal perfusion and kidney volume than B6 mice ( P < 0.05). CD1 mice developed substantial interstitial fibrosis and decreased peritubular capillary (PTC) density by day 14 while B6 mice showed only mild renal scarring and almost normal PTC. Our results show that after IRI, CD1 mice develop more inflammation, hypertension, and later mesangial matrix expansion than B6 mice do. Subsequently, CD1 animals suffer from CKD due to impaired renal perfusion and pronounced permanent loss of peritubular capillaries.
Circadian regulation of kidney function: finding a role for Bmal1
Authors: Zhang Dingguo , Pollock David M.
Published: January 2018

Mounting evidence suggests that there is an internal molecular “clock” within the kidney to help maintain normal renal function. Disturbance of the kidney circadian rhythm may pose a threat to water and electrolyte homeostasis and blood pressure regulation, among many other problems. The identification of circadian genes facilitated a more comprehensive appreciation of the importance of “keeping the body on time”; however, our knowledge is very limited with regard to how circadian genes regulate kidney function. In this brief review, we summarize recent progress in circadian control of renal physiology, with a particular focus on aryl hydrocarbon receptor nuclear translocator-like protein (Arntl1; also called Bmal1).
GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury
Authors: Putz Nathan D. , Shaver Ciara M. , Dufu Kobina , Li Chien-Ming , Xu Qing , Hutchaleelaha Athiwat , Lehrer-Graiwer Josh , Majka Susan M. , Ware Lorraine B. , Bastarache Julie A.
Published: January 2018

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8–15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1β, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury.

NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.
Motor unit territories in human genioglossus estimated with multichannel intramuscular electrodes
Authors: Luu Billy L. , Muceli Silvia , Saboisky Julian P. , Farina Dario , Héroux Martin E. , Bilston Lynne E. , Gandevia Simon C. , Butler Jane E.
Published: January 2018

The discharge patterns of genioglossus motor units during breathing have been well-characterized in previous studies, but their localization and territories are not known. In this study, we used two newly developed intramuscular multichannel electrodes to estimate the territories of genioglossus motor units in the anterior and posterior regions of the muscle. Seven healthy men participated. Each electrode contained fifteen bipolar channels, separated by 1 mm, and was inserted percutaneously below the chin, perpendicular to the skin, to a depth of 36 mm. Single motor unit activity was recorded with subjects awake, supine, and breathing quietly through a nasal mask for 180 s. Motor unit territories were estimated from the spike-triggered averages of the electromyographic signal from each channel. A total of 30 motor units were identified: 22 expiratory tonic, 1 expiratory phasic, 2 tonic, 3 inspiratory tonic, and 2 inspiratory phasic. Motor units appeared to be clustered based on unit type, with peak activities for expiratory units predominantly located in the anterior and superficial fibers of genioglossus and inspiratory units in the posterior region. Of these motor unit types, expiratory tonic units had the largest estimated territory, a mean 11.3 mm (SD 1.9). Estimated territories of inspiratory motor units ranged from 3 to 6 mm. In accordance with the distribution of motor unit types, the estimated territory of genioglossus motor units varied along the sagittal plane, decreasing from anterior to posterior. Our findings suggest that genioglossus motor units have large territories relative to the cross-sectional size of the muscle.

NEW & NOTEWORTHY In this study, we used a new multichannel intramuscular electrode to address a fundamental property of human genioglossus motor units. We describe the territory of genioglossus motor units in the anterior and posterior regions of the muscle and show a decrease in territory size from anterior to posterior and that expiratory-related motor units have larger estimated territories than inspiratory-related motor units.
Unilateral strength training leads to muscle-specific sparing effects during opposite homologous limb immobilization
Authors: Andrushko Justin W. , Lanovaz Joel L. , Björkman Kelsey M. , Kontulainen Saija A. , Farthing Jonathan P.
Published: January 2018

Cross education (CE) occurs after unilateral training whereby performance of the untrained contralateral limb is enhanced. A few studies have shown that CE can preserve or “spare” strength and size of an opposite immobilized limb, but the specificity (i.e., trained homologous muscle and contraction type) of these effects is unknown. The purpose was to investigate specificity of CE “sparing” effects with immobilization. The nondominant forearm of 16 participants was immobilized with a cast, and participants were randomly assigned to a resistance training (eccentric wrist flexion, 3 times/week) or control group for 4 weeks. Pre- and posttesting involved wrist flexors and extensors eccentric, concentric and isometric maximal voluntary contractions (via dynamometer), muscle thickness (via ultrasound), and forearm muscle cross-sectional area (MCSA; via peripheral quantitative computed tomography). Only the training group showed strength preservation across all contractions in the wrist flexors of the immobilized limb (training: −2.4% vs. control: −21.6%; P = 0.04), and increased wrist flexors strength of the nonimmobilized limb (training: 30.8% vs. control: −7.4%; P = 0.04). Immobilized arm MCSA was preserved for the training group only (training: 1.3% vs. control: −2.3%; P = 0.01). Muscle thickness differed between groups for the immobilized (training: 2.8% vs. control: −3.2%; P = 0.01) and nonimmobilized wrist flexors (training: 7.1% vs. control: −3.7%; P = 0.02). Strength preservation was nonspecific to contraction type ( P = 0.69, [Formula: see text] = 0.03) yet specific to the trained flexors muscle. These findings suggest that eccentric training of the nonimmobilized limb can preserve size of the immobilized contralateral homologous muscle and strength across multiple contraction types.

NEW & NOTEWORTHY Unilateral strength training preserves strength, muscle thickness, and muscle cross-sectional area in an opposite immobilized limb. The preservation of size and strength was confined to the trained homologous muscle group. However, strength was preserved across multiple contraction types.
Bayesian quantification of sensory reweighting in a familial bilateral vestibular disorder (DFNA9)
Authors: Alberts Bart B. G. T. , Selen Luc P. J. , Verhagen Wim I. M. , Pennings Ronald J. E. , Medendorp W. Pieter
Published: January 2018

DFNA9 is a rare progressive autosomal dominantly inherited vestibulo-cochlear disorder, resulting in a homogeneous group of patients with hearing impairment and bilateral vestibular function loss. These patients suffer from a deteriorated sense of spatial orientation, leading to balance problems in darkness, especially on irregular surfaces. Both behavioral and functional imaging studies suggest that the remaining sensory cues could compensate for the loss of vestibular information. A thorough model-based quantification of this reweighting in individual patients is, however, missing. Here we psychometrically examined the individual patient’s sensory reweighting of these cues after complete vestibular loss. We asked a group of DFNA9 patients and healthy control subjects to judge the orientation (clockwise or counterclockwise relative to gravity) of a rod presented within an oriented square frame (rod-in-frame task) in three different head-on-body tilt conditions. Our results show a cyclical frame-induced bias in perceived gravity direction across a 90° range of frame orientations. The magnitude of this bias was significantly increased in the patients compared with the healthy control subjects. Response variability, which increased with head-on-body tilt, was also larger for the patients. Reverse engineering of the underlying signal properties, using Bayesian inference principles, suggests a reweighting of sensory signals, with an increase in visual weight of 20–40% in the patients. Our approach of combining psychophysics and Bayesian reverse engineering is the first to quantify the weights associated with the different sensory modalities at an individual patient level, which could make it possible to develop personal rehabilitation programs based on the patient’s sensory weight distribution.

NEW & NOTEWORTHY It has been suggested that patients with vestibular deficits can compensate for this loss by increasing reliance on other sensory cues, although an actual quantification of this reweighting is lacking. We combine experimental psychophysics with a reverse engineering approach based on Bayesian inference principles to quantify sensory reweighting in individual vestibular patients. We discuss the suitability of this approach for developing personal rehabilitation programs based on the patient’s sensory weight distribution.
Contribution of action potentials to the extracellular field potential in the nucleus laminaris of barn owl
Authors: Kuokkanen Paula T. , Ashida Go , Kraemer Anna , McColgan Thomas , Funabiki Kazuo , Wagner Hermann , Köppl Christine , Carr Catherine E. , Kempter Richard
Published: January 2018

Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine whether we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H, Kempter R. J Neurophysiol 110: 117–130, 2013; McColgan T, Liu J, Kuokkanen PT, Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 and 700 Hz, could be attributed to the NL neurons’ spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at frequencies ≳1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible.

NEW & NOTEWORTHY Extracellular field potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s nucleus laminaris. There the EFP originates predominantly from spiking in the afferent axons, with spectral power ≳1 kHz, while postsynaptic laminaris neurons contribute little. In conclusion, the identification of EFP sources is possible if they have different spectral components and if their activities can be modulated selectively.
The influence of acute elevations in plasma osmolality and serum sodium on sympathetic outflow and blood pressure responses to exercise
Authors: Brian Michael S. , Matthews Evan L. , Watso Joseph C. , Babcock Matthew C. , Wenner Megan M. , Rose William C. , Stocker Sean D. , Farquhar William B.
Published: January 2018

Elevated plasma osmolality (pOsm) has been shown to increase resting sympathetic nerve activity in animals and humans. The present study tested the hypothesis that increases in pOsm and serum sodium (sNa+) concentration would exaggerate muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to handgrip (HG) exercise and postexercise ischemia (PEI). BP and MSNA were measured during HG followed by PEI before and after a 23-min hypertonic saline infusion (HSI-3% NaCl). Eighteen participants (age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed the protocol; pOsm and sNa+ increased from pre- to post-HSI (285 ± 1 to 291 ± 1 mosmol/kg H2O; 138.2 ± 0.3 to 141.3 ± 0.4 mM; P < 0.05 for both). Resting mean BP (90 ± 2 vs. 92 ± 1 mmHg) and MSNA (11 ± 2 vs. 15 ± 2 bursts/min) were increased pre- to post-HSI ( P < 0.05 for both). Mean BP responses to HG (106 ± 2 vs. 111 ± 2 mmHg, P < 0.05) and PEI (102 ± 2 vs. 107 ± 2 mmHg, P < 0.05) were higher post-HSI. Similarly, MSNA during HG (20 ± 2 vs. 29 ± 2 bursts/min, P < 0.05) and PEI (19 ± 2 vs. 24 ± 3 bursts/min, P < 0.05) were greater post-HSI. In addition, the change in MSNA was greater post-HSI during HG (Δ9 ± 2 vs. Δ13 ± 3 bursts/min, P < 0.05). A second set of participants ( n = 13, age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed a time control (TC) protocol consisting of quiet rest instead of an infusion. The TC condition yielded no change in resting sNa+, pOsm, mean BP, or MSNA (all P > 0.05); responses to HG and PEI were not different pre- to post-quiet rest ( P > 0.05). In summary, acutely increasing pOsm and sNa+ exaggerates BP and MSNA responses during HG exercise and PEI.

NEW & NOTEWORTHY Elevated plasma osmolality has been shown to increase resting sympathetic activity and blood pressure. This study provides evidence that acute elevations in plasma osmolality and serum sodium exaggerated muscle sympathetic nerve activity and blood pressure responses during exercise pressor reflex activation in healthy young adults.
Beyond the labeled line: variation in visual reference frames from intraparietal cortex to frontal eye fields and the superior colliculus
Authors: Caruso Valeria C. , Pages Daniel S. , Sommer Marc A. , Groh Jennifer M.
Published: January 2018

We accurately perceive the visual scene despite moving our eyes ~3 times per second, an ability that requires incorporation of eye position and retinal information. In this study, we assessed how this neural computation unfolds across three interconnected structures: frontal eye fields (FEF), intraparietal cortex (LIP/MIP), and the superior colliculus (SC). Single-unit activity was assessed in head-restrained monkeys performing visually guided saccades from different initial fixations. As previously shown, the receptive fields of most LIP/MIP neurons shifted to novel positions on the retina for each eye position, and these locations were not clearly related to each other in either eye- or head-centered coordinates (defined as hybrid coordinates). In contrast, the receptive fields of most SC neurons were stable in eye-centered coordinates. In FEF, visual signals were intermediate between those patterns: around 60% were eye-centered, whereas the remainder showed changes in receptive field location, boundaries, or responsiveness that rendered the response patterns hybrid or occasionally head-centered. These results suggest that FEF may act as a transitional step in an evolution of coordinates between LIP/MIP and SC. The persistence across cortical areas of mixed representations that do not provide unequivocal location labels in a consistent reference frame has implications for how these representations must be read out.

NEW & NOTEWORTHY How we perceive the world as stable using mobile retinas is poorly understood. We compared the stability of visual receptive fields across different fixation positions in three visuomotor regions. Irregular changes in receptive field position were ubiquitous in intraparietal cortex, evident but less common in the frontal eye fields, and negligible in the superior colliculus (SC), where receptive fields shifted reliably across fixations. Only the SC provides a stable labeled-line code for stimuli across saccades.
Backward walking highlights gait asymmetries in children with cerebral palsy
Authors: Cappellini Germana , Sylos-Labini Francesca , MacLellan Michael J. , Sacco Annalisa , Morelli Daniela , Lacquaniti Francesco , Ivanenko Yury
Published: January 2018

To investigate how early injuries to developing motor regions of the brain affect different forms of gait, we compared the spatiotemporal locomotor patterns during forward (FW) and backward (BW) walking in children with cerebral palsy (CP). Bilateral gait kinematics and EMG activity of 11 pairs of leg muscles were recorded in 14 children with CP (9 diplegic, 5 hemiplegic; 3.0–11.1 yr) and 14 typically developing (TD) children (3.3–11.8 yr). During BW, children with CP showed a significant increase of gait asymmetry in foot trajectory characteristics and limb intersegmental coordination. Furthermore, gait asymmetries, which were not evident during FW in diplegic children, became evident during BW. Factorization of the EMG signals revealed a comparable structure of the motor output during FW and BW in all groups of children, but we found differences in the basic temporal activation patterns. Overall, the results are consistent with the idea that both forms of gait share pattern generation control circuits providing similar (though reversed) kinematic patterns. However, BW requires different muscle activation timings associated with muscle modules, highlighting subtle gait asymmetries in diplegic children, and thus provides a more comprehensive assessment of gait pathology in children with CP. The findings suggest that spatiotemporal asymmetry assessments during BW might reflect an impaired state and/or descending control of the spinal locomotor circuitry and can be used for diagnostic purposes and as complementary markers of gait recovery.

NEW & NOTEWORTHY Early injuries to developing motor regions of the brain affect both forward progression and other forms of gait. In particular, backward walking highlights prominent gait asymmetries in children with hemiplegia and diplegia from cerebral palsy and can give a more comprehensive assessment of gait pathology. The observed spatiotemporal asymmetry assessments may reflect both impaired supraspinal control and impaired state of the spinal circuitry.
When uncertain, does human self-motion decision-making fully utilize complete information?
Authors: Clark Torin K. , Yi Yongwoo , Galvan-Garza Raquel C. , Bermúdez Rey María Carolina , Merfeld Daniel M.
Published: January 2018

When forced to choose humans often feel uncertain. Investigations of human perceptual decision-making often employ signal detection theory, which assumes that even when uncertain all available information is fully utilized. However, other studies have suggested or assumed that, when uncertain, human subjects guess totally at random, ignoring available information. When uncertain, do humans simply guess totally at random? Or do humans fully utilize complete information? Or does behavior fall between these two extremes yielding “above chance” performance without fully utilizing complete information? While it is often assumed complete information is fully utilized, even when uncertain, to our knowledge this has never been experimentally confirmed. To answer this question, we combined numerical simulations, theoretical analyses, and human studies performed using a self-motion direction-recognition perceptual decision-making task (did I rotate left or right?). Subjects were instructed to make forced-choice binary (left/right) and trinary (left/right/uncertain) decisions when cued following each stimulus. Our results show that humans 1) do not guess at random when uncertain and 2) make binary and trinary decisions equally well. These findings show that humans fully utilize complete information when uncertain for our perceptual decision-making task. This helps unify signal detection theory and other models of forced-choice decision-making which allow for uncertain responses.

NEW & NOTEWORTHY Humans make many perceptual decisions every day. But what if we are uncertain? While many studies assume that humans fully utilize complete information, other studies have suggested and/or assumed that when we're uncertain and forced to decide, information is not fully utilized. While humans tend to perform above chance when uncertain, no earlier study has tested whether available information is fully utilized. Our results show that humans make fully informed decisions even when uncertain.
Robust and tunable bursting requires slow positive feedback
Authors: Franci Alessio , Drion Guillaume , Sepulchre Rodolphe
Published: January 2018

We highlight that the robustness and tunability of a bursting model critically rely on currents that provide slow positive feedback to the membrane potential. Such currents have the ability to make the total conductance of the circuit negative in a timescale that is termed “slow” because it is intermediate between the fast timescale of the spike upstroke and the ultraslow timescale of even slower adaptation currents. We discuss how such currents can be assessed either in voltage-clamp experiments or in computational models. We show that, while frequent in the literature, mathematical and computational models of bursting that lack the slow negative conductance are fragile and rigid. Our results suggest that modeling the slow negative conductance of cellular models is important when studying the neuromodulation of rhythmic circuits at any broader scale.

NEW & NOTEWORTHY Nervous system functions rely on the modulation of neuronal activity between different rhythmic patterns. The mechanisms of this modulation are still poorly understood. Using computational modeling, we show the critical role of currents that provide slow negative conductance, distinct from the fast negative conductance necessary for spike generation. The significance of the slow negative conductance for neuromodulation is often overlooked, leading to computational models that are rigid and fragile.
Age-related erosion of obstacle avoidance reflexes evoked with electrical stimulation of tibial nerve during walking
Authors: Hundza Sandra R. , Gaur Amit , Brodie Ryan , Commandeur Drew , Klimstra Marc D.
Published: January 2018

In young healthy adults, characteristic obstacle avoidance reflexes have been demonstrated in response to electrical stimulation of cutaneous afferents of the foot during walking. It is unknown whether there is an age-related erosion of this obstacle avoidance reflex evoked with stimulation to the tibial nerve innervating the sole of the foot. The purpose of this study was to identify age-dependent differences in obstacle avoidance reflexes evoked with electrical stimulation of the tibial nerve at the ankle during walking in healthy young and older (70 yr and older) adults with no history of falls. Toe clearance, ankle and knee joint displacement and angular velocity, and electromyograms (EMG) of the tibialis anterior, medial gastrocnemius, biceps femoris, and vastus lateralis were measured. A significant erosion of kinematic and EMG obstacle avoidance reflexes was seen in the older adults compared with the young. Specifically, during swing phase, there was reduced toe clearance, ankle dorsiflexion, and knee flexion angular displacement in older adults compared with the young as well as changes in muscle activation. These degraded reflexes were superimposed on altered kinematics seen during unperturbed walking in the older adults including reduced toe clearance and knee flexion and increased ankle dorsiflexion compared with the young. Notably, during mid-swing the toe clearance was reduced in the older adults compared with the young by 2 cm overall, resulting from a combination of 1-cm reduced reflex response in the older adults superimposed on 1-cm less toe clearance during unperturbed walking. Together, these age-related differences could represent the prodromal phase of fall risk.

NEW & NOTEWORTHY This study demonstrated age-dependent erosion of obstacle avoidance reflexes evoked with electrical stimulation of the tibial nerve at the ankle during walking. There was significant reduction in toe clearance, ankle dorsiflexion, and knee flexion reflexes as well as changes in muscle activation during swing phase in older adults with no history of falls compared with the young. These degraded reflexes, superimposed on altered kinematics seen during unperturbed walking, likely represent the prodromal phase of fall risk.
Distinct gene signatures predict insulin resistance in young mice with high fat diet-induced obesity
Authors: Chen Katherine , Jih Alice , Osborn Olivia , Kavaler Sarah T. , Fu Wenxian , Sasik Roman , Saito Rintaro , Kim Jane J.
Published: January 2018

Highly inbred C57BL/6 mice show wide variation in their degree of insulin resistance in response to diet-induced obesity even though they are almost genetically identical. Here we employed transcriptional profiling by RNA sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to determine how gene expression patterns correlate with the later development of high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this goal, we partially removed and banked tissues from pubertal mice. Mice subsequently received HFD followed by metabolic phenotyping to identify two well-defined groups of mice with either severe or mild insulin resistance. The remaining tissues were collected at study termination. We then applied RNA-Seq to generate transcriptome profiles associated with worsened insulin resistance before and after the initiation of HFD. We found 244 up- and 109 downregulated genes in VAT of the most insulin-resistant mice even before HFD exposure. Downregulated genes included serine protease inhibitor, major urinary protein, and complement genes; upregulated genes represented mostly muscle constituents. These gene families were also differentially expressed in VAT of mice with high or low insulin resistance after HFD. Inflammatory genes predicted insulin resistance in liver, but not in VAT. In contrast, when we compared VAT of all mice before and after HFD, differentially expressed genes were predominantly composed of immune response genes. These data show a distinct set of gene transcripts in young mice correlates with the severity of insulin resistance in adulthood, providing insight into the pathogenesis of insulin resistance in early life.
A Wireless Covert Channel Based on Constellation Shaping Modulation
Authors: Cao Pengcheng , Liu Weiwei , Liu Guangjie , Ji Xiaopeng , Zhai Jiangtao , Dai Yuewei
Published: January 2018

Wireless covert channel is an emerging covert communication technique which conceals the very existence of secret information in wireless signal including GSM, CDMA, and LTE. The secret message bits are always modulated into artificial noise superposed with cover signal, which is then demodulated with the shared codebook at the receiver. In this paper, we first extend the traditional KS test and regularity test in covert timing channel detection into wireless covert channel, which can be used to reveal the very existence of secret data in wireless covert channel from the aspect of multiorder statistics. In order to improve the undetectability, a wireless covert channel for OFDM-based communication system based on constellation shaping modulation is proposed, which generates additional constellation points around the standard points in normal constellations. The carrier signal is then modulated with the dirty constellation and the secret message bits are represented by the selection mode of the additional constellation points; shaping modulation is employed to keep the distribution of constellation errors unchanged. Experimental results show that the proposed wireless covert channel scheme can resist various statistical detections. The communication reliability under typical interference is also proved.
Multifunctional Amine Mesoporous Silica Spheres Modified with Multiple Amine as Carriers for Drug Release
Authors: Li Yan , Song Fangxiang , Guo Yu , Cheng Liang , Chen Qianlin
Published: January 2018

Mesoporous silica spheres were synthesized by using Stöber theory (MSN-40). Calcination of the mesostructured phase resulted in the starting solid. Organic modification with aminopropyl groups resulted in two MSN-40 materials: named MSN-NH2 and MSN-DQ-40, respectively. These two kinds of samples with different pore sizes (obtained from 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethox-ysilane (NQ-62) and modified NQ-62) showed control of the delivery rate of ibuprofen (IBU) from the siliceous matrix. The obtained sample from modified NQ-62 has an increased loading rate and shows better control of the delivery rate of IBU than the obtained sample from NQ-62. These three solids were characterized using standard solid state procedures. During tests of in vitro drug release, an interesting phenomenon was observed: at high pH (pH 7.45), IBU in all carriers was released slowly; at low pH (pH 4.5), only a part of the IBU was slowly released from this carrier within 25 hours; most IBU was effectively confined in mesoporous material, but the remaining IBU was released rapidly and completely after 25 hours.
A Study on Internal Explosion Testing of the “Rigid‐Flexible‐Rigid” Three‐Layer Sealed Structure
Authors: Xue Y. L. , Tang D. G. , Li Z. Z. , Shao L. Z. , Liao Z. , Chen W. X. , Zhen R. L.
Published: January 2018

Multilayered combination of protective structures is an important means of effectively weakening the explosive shockwave. On this basis, a “rigid‐flexible‐rigid” three‐layer sealed structure was proposed in this paper and two models for the sealed structure were designed. Meanwhile, internal explosion tests of the two models were conducted. One model used foam concrete as the energy absorbing material and the other used dense sand. The comparisons between the test results and the computed results obtained from the formulae were made, and the test results agreed well with the computed results. Test results showed that both models had favorable energy‐dissipating capacity, and the model that used foam concrete as the energy absorbing material had a superior energy‐dissipating capacity.
Juxta-Vascular Pulmonary Nodule Segmentation in PET-CT Imaging Based on an LBF Active Contour Model with Information Entropy and Joint Vector
Authors: Hao Rui , Qiang Yan , Yan Xiaofei
Published: January 2018

The accurate segmentation of pulmonary nodules is an important preprocessing step in computer-aided diagnoses of lung cancers. However, the existing segmentation methods may cause the problem of edge leakage and cannot segment juxta-vascular pulmonary nodules accurately. To address this problem, a novel automatic segmentation method based on an LBF active contour model with information entropy and joint vector is proposed in this paper. Our method extracts the interest area of pulmonary nodules by a standard uptake value (SUV) in Positron Emission Tomography (PET) images, and automatic threshold iteration is used to construct an initial contour roughly. The SUV information entropy and the gray-value joint vector of Positron Emission Tomography–Computed Tomography (PET-CT) images are calculated to drive the evolution of contour curve. At the edge of pulmonary nodules, evolution will be stopped and accurate results of pulmonary nodule segmentation can be obtained. Experimental results show that our method can achieve 92.35% average dice similarity coefficient, 2.19 mm Hausdorff distance, and 3.33% false positive with the manual segmentation results. Compared with the existing methods, our proposed method that segments juxta-vascular pulmonary nodules in PET-CT images is more accurate and efficient.
Change of Safe Needling Depth at Acupoint GB21 according to Posture and Breathing
Authors: Chu Hongmin , Kim Jaehyun , Ha Wonbae , Cho Eunbyul , Kang Geon , Park Seongjun , Jang Jongwon , Yang Seung Bum , Kang Yeonseok , Lee Sanghun , Kim Jae-Hyo
Published: January 2018

Acupoint GB21 (Jianjing) is used for treating back and shoulder pain but is associated with a risk of pneumothorax. We aimed to determine the SND (safe needling depth) at GB21 according to posture and breathing in real time. Ultrasonographic images of GB21 during normal breathing, inspiration, and expiration in a SP (sitting position) were acquired for 52 healthy volunteers. Images were also acquired during normal respiration in the PP (prone position) with arms raised and lowered. The average SND was greater for men than for women (p < 0.05). Analysis of variance revealed that the SND was greater for the PP than for the SP (p = 0.01 and p < 0.05, resp.). Although the SND tended to change according to posture, the average depth tended to deviate widely in some subjects. During breathing, the differences between inspiration and expiration were less than 1 mm in most subjects, but some showed differences more than 4.5 mm. The SND at GB21 was greater in overweight subjects and significantly greater in the PP and during maximal expiration. However, intragroup differences were greater than the intergroup differences. Therefore, it is dangerous to simply apply needling depth on a gender or BMI basis. The practitioner would adjust the SND by examining the individual anatomical structures.
Proportional Load Sharing and Stability of DC Microgrid with Distributed Architecture Using SM Controller
Authors: Rashad Muhammad , Raoof Uzair , Ashraf Muhammad , Ashfaq Ahmed Bilal
Published: January 2018

DC microgrids look attractive in distribution systems due to their high reliability, high efficiency, and easy integration with renewable energy sources. The key objectives of the DC microgrid include proportional load sharing and precise voltage regulation. Droop controllers are based on decentralized control architectures which are not effective in achieving these objectives simultaneously due to the voltage error and load power variation. A centralized controller can achieve these objectives using a high speed communication link. However, it loses reliability due to the single point failure. Additionally, these controllers are realized through proportional integral (PI) controllers which cannot ensure load sharing and stability in all operating conditions. To address limitations, a distributed architecture using sliding mode (SM) controller utilizing low bandwidth communication is proposed for DC microgrids in this paper. The main advantages are high reliability, load power sharing, and precise voltage regulation. Further, the SM controller shows high robustness, fast dynamic response, and good stability for large load variations. To analyze the stability and dynamic performance, a system model is developed and its transversality, reachability, and equivalent control conditions are verified. Furthermore, the dynamic behavior of the modeled system is investigated for underdamped and critically damped responses. Detailed simulations are carried out to show the effectiveness of the proposed controller.
An Imputation Method for Missing Traffic Data Based on FCM Optimized by PSO-SVR
Authors: Shang Qiang , Yang Zhaosheng , Gao Song , Tan Derong
Published: January 2018

Missing traffic data are inevitable due to detector failure or communication failure. Currently, most of imputation methods estimated the missing traffic values by using spatial-temporal information as much as possible. However, it ignores an important fact that spatial-temporal information of the traffic missing data is often incomplete and unavailable. Moreover, most of the existing methods are verified by traffic data from freeway, and their applicability to urban road data needs to be further verified. In this paper, a hybrid method for missing traffic data imputation is proposed using FCM optimized by a combination of PSO algorithm and SVR. In this method, FCM is the basic algorithm and the parameters of FCM are optimized. Firstly, the patterns of missing traffic data are analyzed and the representation of missing traffic data is given using matrix-based data structure. Then, traffic data from urban expressway and urban arterial road are used to analyze spatial-temporal correlation of the traffic data for the determination of the proposed method input. Finally, numerical experiment is designed from three perspectives to test the performance of the proposed method. The experimental results demonstrate that the novel method not only has high imputation precision, but also exhibits good robustness.
An Optical Fiber Liquid Level Sensor Based on Side Coupling Induction Technology
Authors: Zhang Yanjun , Zhang Yingzi , Hou Yulong , Zhang Liang , Hu Yanjun , Gao Xiaolong , Zhang Huixin , Liu Wenyi
Published: January 2018

An optical fiber liquid level sensor based on two twisted polymer optical fibers twining around a racetrack column is demonstrated in this study. The side-coupling power of the passive fiber is modulated by the refractive index (RI) of the environment medium and decreases while the liquid level increases. The variation patterns of the side-coupling power in the bent section and the straight section form a step attenuation, which can improve the measurement range with a superior sensitivity and distinguish liquids with different RIs. Furthermore, the cost-effective sensor also shows good reversibility and low temperature-dependent properties.
Studies on the Dual Cytotoxicity and Antioxidant Properties of Berberis vulgaris Extracts and Its Main Constituent Berberine
Authors: El khalki Lamyae , Tilaoui Mounir , Jaafari Abdeslam , Ait Mouse Hassan , Zyad Abdelmajid
Published: January 2018

The present study attempts to investigate the cytotoxic activity of ethanol and ethyl acetate extracts of the Moroccan Berberis vulgaris and its major component berberine, together with exploring their antioxidant properties. It also consists of studying the combination effect of berberine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, against the human breast adenocarcinoma cell line (MCF-7). Using the MTT assay, we report a differential cytotoxic effect of ethanol and ethyl acetate extracts since the ethanol extract is more cytotoxic than the ethyl acetate one, with IC50 = 3.54 μg/mL and 596.71 μg/mL, respectively. Interestingly, no cytotoxic effect was observed against normal cells. Furthermore, these extracts showed a remarkable antioxidant activity as measured by the DPPH free radicals scavenging assay. In fact, the IC50 values are 69.65 μg/mL and 77.75 μg/mL for the ethanol and ethyl acetate extracts, respectively. In addition, several concentrations of berberine, when combined with the NO donor used at IC30, induced a synergistic cytotoxic activity at concentrations ranging from 8.40 μM to 33.60 μM, as revealed by the combination index values, using the Chou–Talalay method. However, at the other concentrations tested, an antagonistic effect was observed. The observed cytotoxicity was related to apoptosis induction as demonstrated by the annexin-V-streptavidin FITC-staining analysis.