scholarly journals Quantitative and temporal measurement of dynamic autophagy rates

2021 ◽  
Author(s):  
Nitin Sai Beesabathuni ◽  
Priya S. Shah

AbstractAutophagy is a multistep degradative process that is essential for maintaining cellular homeostasis. Systematically quantifying flux through this pathway is critical for gaining fundamental insights and effectively modulating this process that is dysregulated during many diseases. Established methods to quantify flux use steady state measurements, which provide limited information about the perturbation and the cellular response. We present a theoretical and experimental framework to measure autophagic steps in the form of rates under non-steady state conditions. We use this approach to measure temporal responses to rapamycin and wortmannin treatments, two commonly used autophagy modulators. We quantified changes in autophagy rates in as little as 10 minutes, which can establish direct mechanisms for autophagy perturbation before feedback begins. We identified concentration-dependent effects of rapamycin on the initial and temporal progression of autophagy rates. We also found variable recovery time from wortmannin’s inhibition of autophagy, which is further accelerated by rapamycin. In summary, this new approach enables the quantification of autophagy flux with high sensitivity and temporal resolution and facilitates a comprehensive understanding of this process.

2021 ◽  
Vol 15 ◽  
Author(s):  
Deepak K. Ravi ◽  
Caroline C. Heimhofer ◽  
William R. Taylor ◽  
Navrag B. Singh

For humans, the ability to effectively adapt footfall rhythm to perturbations is critical for stable locomotion. However, only limited information exists regarding how dynamic stability changes when individuals modify their footfall rhythm. In this study, we recorded 3D kinematic activity from 20 participants (13 males, 18–30 years old) during walking on a treadmill while synchronizing with an auditory metronome sequence individualized to their baseline walking characteristics. The sequence then included unexpected temporal perturbations in the beat intervals with the subjects required to adapt their footfall rhythm accordingly. Building on a novel approach to quantify resilience of locomotor behavior, this study found that, in response to auditory perturbation, the mean center of mass (COM) recovery time across all participants who showed deviation from steady state (N = 15) was 7.4 (8.9) s. Importantly, recovery of footfall synchronization with the metronome beats after perturbation was achieved prior (+3.4 [95.0% CI +0.1, +9.5] s) to the recovery of COM kinematics. These results highlight the scale of temporal adaptation to perturbations and provide implications for understanding regulation of rhythm and balance. Thus, our study extends the sensorimotor synchronization paradigm to include analysis of COM recovery time toward improving our understanding of an individual’s resilience to perturbations and potentially also their fall risk.


2019 ◽  
Author(s):  
Xiaomin Zhang ◽  
Keshi Zhang

AbstractOxya chinensisis one of the most widespread grasshopper species found in China and one of the most common pests against rice. Due to the importance of haemocytes in insect immunity and limited information on the haemocytes ofO. chinensis, their haemocytes were examined in detail. The cellular response of the grasshopper was challenged with bacteriaEscherichia coli,Staphylococcus aureusandBacillus subtilis. The morphology of the haemocytes was illustrated by the use of light, scanning electron and transmission electron microscopy, where different morphological varieties of haemocytes were observed. Granulocytes and plasmatocytes responded to the challenged bacteria by phagocytosis. The histochemical staining has indicated the presence of acid phosphatase in plasmatocytes and granulocytes. Non-phagocytic prohemocytes and vermicytes were noticed, but their functions in the circulation are unclear. Our results demonstrate an essential role of plasmatocytes and granulocytes in the innate immunity ofO. chinensis. Insect haemocytes play a crucial role in cellular immunity, and further research is needed for a comprehensive understanding.Summary statementThe cellular response was used byOxya chinensisagainst the bacterial challenges where two types of haemocytes shared the duty of phagocytosis.


Author(s):  
Rohit S Loomba ◽  
Enrique G Villarreal ◽  
Juan S Farias ◽  
Gaurav Aggarwal ◽  
Saurabh Aggarwal ◽  
...  

Background There is limited information regarding the role of biomarker levels at predicting mortality in patients with the novel coronavirus pandemic (Covid-19). The purpose of this study is to determine the differences in serum biomarker levels in adults with Covid-19 who survived hospitalization from those who did not. Methods A comprehensive search was completed on PubMed, EMBASE, and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. Results A total of 10 studies with 1,584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from Covid-19 (coronavirus disease 2019) included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukins 6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and creatinine. Lymphocyte count, platelet count, and albumin were significantly lower in patients who died. Conclusion This pooled analysis of 10 studies including 1,584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited healthcare resources.


Author(s):  
Yan Chen ◽  
Ward Whitt

In order to understand queueing performance given only partial information about the model, we propose determining intervals of likely values of performance measures given that limited information. We illustrate this approach for the mean steady-state waiting time in the $GI/GI/K$ queue. We start by specifying the first two moments of the interarrival-time and service-time distributions, and then consider additional information about these underlying distributions, in particular, a third moment and a Laplace transform value. As a theoretical basis, we apply extremal models yielding tight upper and lower bounds on the asymptotic decay rate of the steady-state waiting-time tail probability. We illustrate by constructing the theoretically justified intervals of values for the decay rate and the associated heuristically determined interval of values for the mean waiting times. Without extra information, the extremal models involve two-point distributions, which yield a wide range for the mean. Adding constraints on the third moment and a transform value produces three-point extremal distributions, which significantly reduce the range, producing practical levels of accuracy.


1990 ◽  
Vol 10 (1) ◽  
pp. 391-396
Author(s):  
L Hu ◽  
L J Gudas

Retinoic acid (RA) receptor alpha (RAR alpha) and RAR gamma steady-state mRNA levels remained relatively constant over time after the addition of RA to F9 teratocarcinoma stem cells. In contrast, the steady-state RAR beta mRNA level started to increase within 12 h after the addition of RA and reached a 20-fold-higher level by 48 h. This RA-associated RAR beta mRNA increase was not prevented by protein synthesis inhibitors but was prevented by the addition of cyclic AMP analogs. In the presence of RA, cyclic AMP analogs also greatly reduced the RAR alpha and RAR gamma mRNA levels, even though cyclic AMP analogs alone did not alter these mRNA levels. The addition of either RA or RA plus cyclic AMP analogs did not result in changes in the three RAR mRNA half-lives. These results suggest that agents which elevate the internal cyclic AMP concentration may also affect the cellular response to RA by altering the expression of the RARs.


Author(s):  
Eisuke Higuchi ◽  
Hiroshi Yabuno ◽  
Yasuyuki Yamamoto ◽  
Sohei Matsumoto

Abstract In recent years, measurement methods that use resonators as microcantilevers have attracted attention because of their high sensitivity, high accuracy, and rapid response time. They have been widely utilized in mass sensing, stiffness sensing, and atomic force microscopy (AFM), among other applications. In all these methods, it is essential to accurately detect shifts in the natural frequency of the resonator caused by an external force from a measured object or sample. Experimental approaches based on self-excited oscillation enable the detection of these shifts even when the resonator is immersed in a high-viscosity environment. In the present study, we experimentally and theoretically investigate the nonlinear characteristics of a microcantilever resonator and their control by nonlinear feedback. We show that the steady-state response amplitude and the corresponding response frequency can be controlled by cubic nonlinear velocity feedback and cubic nonlinear displacement feedback, respectively. Furthermore, the amplitude and frequency of the steady-state self-excited oscillation can be controlled separately. These results will expand application of measurement methods that use self-excited resonators.


2020 ◽  
Vol 1 (1) ◽  
pp. 61-72
Author(s):  
Carlos Bardavío Antón

The field of cults, and that of destructive or coercive cults in particular, has received little attention from the perspective of criminal law doctrine. Supporters of such groups often claim to be victims of a violation related to freedom of will. In this article, I consider various methodologies and manipulation techniques used by such groups and suggest that comparative law, criminal definitions, and regulatory problems provide the basis for a more comprehensive understanding of criminal phenomenology that includes these concerns: the loss of freedom through coercive persuasion, and thus being the victim of a crime, or through becoming an instrument for the commission of crimes ordered by third parties. Research shows that the conventional definition of crime against freedom of will and physical injury is inadequate. I posit that a new approach to legal doctrine and criminal classification is required to fight against new crime phenomenology. I propose a criminal classification aimed at considering coercive persuasion as a crime, and a definition for the criminalization of certain organizations that engage in willful misconduct or reckless conduct.


2017 ◽  
Vol 127 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Stefan Rampp ◽  
Leonhard Rensch ◽  
Sebastian Simmermacher ◽  
Torsten Rahne ◽  
Christian Strauss ◽  
...  

OBJECTIVEBrainstem auditory evoked potentials (BAEPs) have been used for intraoperative monitoring of the auditory nerve for many years. However, BAEPs yield limited information about the expected postoperative hearing quality and speech perception. The auditory steady-state response (ASSR) enables objective audiograms to be obtained in patients under anesthesia. These ASSRs could be used for intraoperative estimation of hearing classes to improve the postoperative outcome and quality of life. Studies investigating the clinical use of ASSRs during total intravenous anesthesia are currently lacking. The work presented in this article therefore investigates the application of ASSRs for intraoperative estimation of hearing classes.METHODSIn 43 patients undergoing surgery for vestibular schwannoma, ASSR measurements were performed at the beginning and end of the surgical procedure. ASSR stimuli consisted of 80-dB hearing level amplitude-modulated tones with 5-minute duration, 90-Hz modulation, and 3 different carrier frequencies: 500, 1000, and 2000 Hz. Stimulation was performed unilaterally with and without contralateral masking, using single and combined carriers. Evoked responses were recorded and analyzed in the frequency domain. ASSRs were compared with extraoperative hearing classes and BAEPs using ANOVA, correlation, and receiver operating characteristic statistics.RESULTSASSRs yielded high and consistent area under the curve (AUC) values (mean 0.83) and correlation values (mean −0.63), indicating reliable prediction of hearing classes. Analysis of BAEP amplitude changes showed lower AUC (mean 0.79) and correlation values (0.63, 0.37, and 0.50 for Waves I, III, and V, respectively). Latencies showed low AUC values (mean 0.6) and no significant correlation. Combination of several carriers for simultaneous evaluation reduced ASSR amplitudes and respective AUC values. Contralateral masking did not show a significant effect.CONCLUSIONSASSRs robustly estimate hearing class in patients under total intravenous anesthesia, even when using short measurement durations. The method provides a diagnostic performance that exceeds conventional BAEP monitoring and enables objective and automated evaluation. On the basis of these findings, continuous intraoperative auditory monitoring could become a promising alternative or adjunct to BAEPs.


Sign in / Sign up

Export Citation Format

Share Document