bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Nkx2.8 Inhibits Epithelial–Mesenchymal Transition in Bladder Urothelial Carcinoma via Transcriptional Repression of Twist1
Authors: Yu Chunping , Liu Zhuowei , Chen Qiuhong , Li Yonghong , Jiang Lijuan , Zhang Zhiling , Zhou Fangjian 
Published: January 2018

Abstract
Epithelial-to-mesenchymal transition (EMT) promotes metastasis, which is the main cause of bladder urothelial carcinoma–related death. Loss of the candidate tumor-suppressor gene Nkx2.8 has been associated with urothelial carcinoma lymph node metastasis. Here, we show that enforced expression of Nkx2.8 is sufficient to inhibit EMT, reduce motility, and blunt invasiveness of urothelial carcinoma cells. Mechanistic investigations showed that Nkx2.8 negatively regulated expression of the EMT inducer Twist1 in urothelial carcinoma cells, at both the level of mRNA and protein accumulation. Nkx2.8 bound directly to the promoter region of this gene and transcriptionally repressed its expression. Twist1 upregulation reversed EMT inhibition by Nkx2.8, restoring the invasive phenotype of urothelial carcinoma cells. In clinical urothelial carcinoma specimens, expression of Nkx2.8 inversely correlated with Twist1 expression, and urothelial carcinoma patients with Nkx2.8 positivity and low Twist1 expression displayed the best prognosis. Our findings highlight the Nkx2.8–Twist1 axis as candidate target for therapeutic intervention in advanced urothelial carcinoma.
Significance: These findings highlight a novel EMT signaling axis as a candidate target for therapeutic intervention in advanced urothelial carcinomas. Cancer Res; 78(5); 1241–52. ©2018 AACR.
Development of Chemotherapy with Cell-Cycle Inhibitors for Adult and Pediatric Cancer Therapy
Authors: Mills Christopher C. , Kolb EA. , Sampson Valerie B. 
Published: January 2018

Abstract
Preclinical and clinical development of agents that inhibit cell-cycle progression have brought an understanding of the feasibility of targeting various cell-cycle regulators in patients with cancer. Small molecule inhibitors targeting key proteins that participate in cell-cycle progression including the cyclin-dependent kinases and checkpoint kinases induce cell-cycle arrest and apoptosis in neoplastic cells. Early phase I studies demonstrate targeted inhibitors can be administered safely in adult and pediatric cancer patients, but these agents generally show limited clinical benefits as single agents. In this review, we discuss biological mechanisms that support dual combination strategies of cell-cycle inhibition with chemotherapeutic agents that are anticipated to achieve rationally targeted therapies for cancer patients. The rationale for evaluating these combination strategies is that DNA damage renders tumors highly responsive to irreversible cell-cycle arrest therapy. This approach is predicted to generate less intensive therapies and to maximize the efficacy of individual agents against solid tumors and hematologic malignancies. Cancer Res; 78(2); 320–5. ©2018 AACR.
Reversing the Cardiac Effects of Sedentary Aging in Middle Age—A Randomized Controlled Trial
Authors: Howden Erin J. , Sarma Satyam , Lawley Justin S. , Opondo Mildred , Cornwell William , Stoller Douglas , Urey Marcus A. , Adams-Huet Beverley , Levine Benjamin D. 
Published: January 2018

Background:
Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness.

Methods:

Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo
2
max) was measured to quantify changes in fitness.

Results:

Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo
2
max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time
P
<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268,
P
=0.0018), whereas there was no change in controls (group×time
P
<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031,
P
=0.83). Exercise increased LV end-diastolic volume (group×time
P
<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time
P
=0.007).

Conclusions:
In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02039154.
Real‐Time Analysis of the Heart Rate Variability During Incremental Exercise for the Detection of the Ventilatory Threshold
Authors: Shiraishi Yasuyuki , Katsumata Yoshinori , Sadahiro Taketaro , Azuma Koichiro , Akita Keitaro , Isobe Sarasa , Yashima Fumiaki , Miyamoto Kazutaka , Nishiyama Takahiko , Tamura Yuichi , Kimura Takehiro , Nishiyama Nobuhiro , Aizawa Yoshiyasu , Fukuda Keiichi , Takatsuki Seiji 
Published: January 2018

Background

It has never been possible to immediately evaluate heart rate variability (
HRV
) during exercise. We aimed to visualize the real‐time changes in the power spectrum of
HRV
during exercise and to investigate its relationship to the ventilatory threshold (
VT
).

Methods and Results

Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an
RAMP
protocol ergometer. The
HRV
was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (
HF
) was followed by a drastic shift in the power spectrum of the
HRV
with a periodic augmentation in the low frequency/
HF
(L/H) and steady low
HF
. When the
HRV
threshold (
HRVT
) was defined as conversion from a predominant high frequency (
HF
) to a predominant low frequency/
HF
(L/H), the
VO
2
at the
HRVT
(
HRVT
‐
VO
2
) was substantially correlated with the
VO
2
at the lactate threshold and
VT
) in the healthy subjects (
r
=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and
HRVT
, 0.53 mL/kg per minute for
VT
and
HRVT
) was nonsignificant (
P
>0.05). Furthermore, the
HRVT
‐
VO
2
was also correlated with the
VT
‐
VO
2
in these myocardial infarction patients (
r
=0.867), and the mean difference was −0.72 mL/kg per minute and was nonsignificant (
P
>0.05).

Conclusions

A
HRV
analysis with our method enabled real‐time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the
VT
.