response profiles
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Author(s):  
Maximilien Franck ◽  
Juan de Toro-Martín ◽  
Thibault V. Varin ◽  
Véronique Garneau ◽  
Geneviève Pilon ◽  
...  

2021 ◽  
pp. 1-22
Author(s):  
Dinavahi V. P. S. Murty ◽  
Songtao Song ◽  
Kelly Morrow ◽  
Jongwan Kim ◽  
Kesong Hu ◽  
...  

Abstract In the present fMRI study, we examined how anxious apprehension is processed in the human brain. A central goal of the study was to test the prediction that a subset of brain regions would exhibit sustained response profiles during threat periods, including the anterior insula, a region implicated in anxiety disorders. A second important goal was to evaluate the responses in the amygdala and the bed nucleus of the stria terminals, regions that have been suggested to be involved in more transient and sustained threat, respectively. A total of 109 participants performed an experiment in which they encountered “threat” or “safe” trials lasting approximately 16 sec. During the former, they experienced zero to three highly unpleasant electrical stimulations, whereas in the latter, they experienced zero to three benign electrical stimulations (not perceived as unpleasant). The timing of the stimulation during trials was randomized, and as some trials contained no stimulation, stimulation delivery was uncertain. We contrasted responses during threat and safe trials that did not contain electrical stimulation, but only the potential that unpleasant (threat) or benign (safe) stimulation could occur. We employed Bayesian multilevel analysis to contrast responses to threat and safe trials in 85 brain regions implicated in threat processing. Our results revealed that the effect of anxious apprehension is distributed across the brain and that the temporal evolution of the responses is quite varied, including more transient and more sustained profiles, as well as signal increases and decreases with threat.


2021 ◽  
Author(s):  
Ester Amorim ◽  
Marton Kaique Andrade Cavalcante ◽  
Ailton Alvaro Silva ◽  
Vanessa Lucília Silveira Medeiros ◽  
Maria Edileuza Felinto Brito ◽  
...  

Abstract Cutaneous leishmaniasis is an infectious disease that presents an immune response marked by the activation of lymphocytes and production of cytokines, including those of the IL-1 family, which act as an important trigger for the activation of an effector immune response. Despite this, inflammation exacerbation is sometimes also attributed to IL-1 cytokines, although some others down-regulate inflammation or produce Th2 responses, which need to be further clarified in the CL. Assessing the gene and protein expression of IL-1 cytokines associated with different immune response profiles in PBMCs from patients with active and healed lesions, this study demonstrated that stimulation by L. braziliensis positively regulates inflammatory and anti-inflammatory IL-1 cytokines, as IL-1α/β and IL-37, while there was a marked inhibition of IL-1Ra and IL-18 genes in patients treated with antimony, which perhaps contributes to the mechanisms of resistance that control Leishmania infection.


Chemosensors ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 346
Author(s):  
Elisa Ruiz ◽  
Thiaka Gueye ◽  
Claire Masson ◽  
Christelle Varenne ◽  
Alain Pauly ◽  
...  

To fabricate mass and resistive sensors based on reduced graphene oxide (RGO), we investigated the functionalization of RGO by tetra tert-butyl phthalocyanine (PcH2tBu), which possesses a macroring and tert-butyl peripheral groups. Herein, we present the gas sensor responses of the functionalized RGO toward benzene, toluene, and xylene (BTX) vapors. The RGO was obtained by the reduction of graphene oxide (GO) using citrate as a reducing agent, while the functionalization was achieved non-covalently by simply using ultrasonic and heating treatment. The sensor devices based on both QCM (quartz crystal microbalance) and resistive transducers were used simultaneously to understand the reactivity. Both the GO and the RGO showed less sensitivity to BTX vapors, while the RGO/PcH2tBu presented enhanced sensor responses. These results show that the p-network plays a very important role in targeting BTX vapors. The resistive response analysis allowed us to state that the RGO is a p-type semiconductor and that the interaction is governed by charge transfer, while the QCM response profiles allowed use to determine the differences between the BTX vapors. Among BTX, benzene shows the weakest sensitivity and a reactivity in the higher concentration range (>600 ppm). The toluene and xylene showed linear responses in the range of 100–600 ppm.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tea Pemovska ◽  
Johannes W. Bigenzahn ◽  
Ismet Srndic ◽  
Alexander Lercher ◽  
Andreas Bergthaler ◽  
...  

AbstractInterrogation of cellular metabolism with high-throughput screening approaches can unravel contextual biology and identify cancer-specific metabolic vulnerabilities. To systematically study the consequences of distinct metabolic perturbations, we assemble a comprehensive metabolic drug library (CeMM Library of Metabolic Drugs; CLIMET) covering 243 compounds. We, next, characterize it phenotypically in a diverse panel of myeloid leukemia cell lines and primary patient cells. Analysis of the drug response profiles reveals that 77 drugs affect cell viability, with the top effective compounds targeting nucleic acid synthesis, oxidative stress, and the PI3K/mTOR pathway. Clustering of individual drug response profiles stratifies the cell lines into five functional groups, which link to specific molecular and metabolic features. Mechanistic characterization of selective responses to the PI3K inhibitor pictilisib, the fatty acid synthase inhibitor GSK2194069, and the SLC16A1 inhibitor AZD3965, bring forth biomarkers of drug response. Phenotypic screening using CLIMET represents a valuable tool to probe cellular metabolism and identify metabolic dependencies at large.


2021 ◽  
Vol 130 (19) ◽  
pp. 195101
Author(s):  
M. L. Chithambo ◽  
J. M. Kalita

2021 ◽  
Author(s):  
Sila Kose ◽  
Recep Ahan ◽  
Ilkay Koksaldi ◽  
Muazzez Olgac ◽  
Cigdem Kasapkara ◽  
...  

The number of synthetic biology based solutions employed in the medical industry is growing every year. The whole cell biosensors being one of them, have been proven valuable tools for developing low-cost, portable, personalized medicine alternatives to conventional techniques. Based on this concept, we targeted one of the major health problems in the world, Chronic Kidney Disease (CKD). To do so, we developed two novel biosensors for the detection of two important renal biomarkers; urea and uric acid. Using advanced gene expression control strategies we improved the operational range and the response profiles of each biosensor to meet clinical specifications. We further engineered these systems to enable multiplexed detection as well as an AND-logic gate operating system. Finally, we tested the applicability of these systems and optimized their working dynamics inside complex medium human blood serum. This study could help the efforts to transition from labor-intensive and expensive laboratory techniques to widely available, portable, low cost diagnostic options.


2021 ◽  
Author(s):  
Suryadeep Dash ◽  
Dawn M Autio ◽  
Shane R Crandall

Layer 6 corticothalamic (L6 CT) neurons are in a strategic position to control sensory input to the neocortex, yet we understand very little about their functions. Apart from studying their anatomical, physiological and synaptic properties, most recent efforts have focused on the activity-dependent influences CT cells can exert on thalamic and cortical neurons through causal optogenetic manipulations. However, few studies have attempted to study them during behavior. In an attempt to address this gap, we performed juxtacellular recordings from optogenetically identified CT neurons in whisker-related primary somatosensory cortex (wS1) of awake, head-fixed mice (of either sex) free to rest quietly or self-initiate bouts of whisking and locomotion. We found a rich diversity of response profiles exhibited by CT cells. Broadly, their spiking patterns were either modulated by whisker-related behavior (~28%) or not (~72%). Whisker-related neurons exhibited both increases as well as decreases in firing rates. We also encountered cells with preceding modulations in firing rate before whisking onset. Overall, whisking better explained these changes in rates than overall changes in arousal. The CT cells that showed no whisker-related activity had low spontaneous firing rates (<0.5 Hz), with many all but silent. Remarkably, this relatively silent population preferentially spiked at the state transition point when pupil diameter constricted and the mouse entered quiet wakefulness. Thus, our results demonstrate that L6 CT neurons in wS1 show diverse spiking patterns, perhaps subserving distinct functional roles related to precisely timed responses during complex behaviors and transitions between discrete waking states.


2021 ◽  
Author(s):  
Aran Nayebi ◽  
Alexander Attinger ◽  
Malcolm G. Campbell ◽  
Kiah Hardcastle ◽  
Isabel I.C. Low ◽  
...  

Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC --- e.g. grid, border, and head-direction cells --- whose highly stereotypical response profiles are suggestive of the role they might play in supporting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more "heterogeneous" cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggesting that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles --- including those of grid cells themselves --- despite not being explicitly trained for this purpose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed "in-silica" experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells are also responsive to non-spatial rewards, we introduce a new MEC model that performs reward-modulated path integration. We find that this unified model matches neural recordings across all variable-reward conditions. Taken together, our results point toward a conceptually principled goal-driven modeling approach for moving future experimental and computational efforts beyond overly-simplistic single-cell stereotypes.


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