scholarly journals PICASSO: Ultra-multiplexed fluorescence imaging of biomolecules through single-round imaging and blind source unmixing

2021 ◽  
Author(s):  
Junyoung Seo ◽  
Yeonbo Sim ◽  
Jeewon Kim ◽  
Hyunwoo Kim ◽  
In Cho ◽  
...  

ABSTRACTUltra-multiplexed fluorescence imaging of biomolecules is essential to studying heterogeneous biological systems. However, this is challenging due to fluorophores’ spectral overlap and variation of the emission spectra. Here, we propose a strategy termed PICASSO, which enables more than 15-colour multiplexed imaging of thick tissue slices through a single imaging process and blind unmixing without reference spectra measurement. We show that PICASSO can be used to achieve a high multiplexing capability in diverse applications, such as 3D protein imaging, expansion microscopy, tissue clearing, imaging of clinical specimens, and cyclic immunofluorescence imaging. PICASSO only requires an equal number of images as the number of fluorophores, enabling such a high level of multiplexed imaging even with bandpass filter-based microscopy. As such, PICASSO would be a useful tool for the study of cancer, the immune system, and the brain, as well as for the diagnosis of cancer, as it enables ultra-multiplexed imaging of diverse specimens with minimum instrumental requirements and experimental processes.

2021 ◽  
pp. 1-15
Author(s):  
Leor Zmigrod

Abstract Ideological behavior has traditionally been viewed as a product of social forces. Nonetheless, an emerging science suggests that ideological worldviews can also be understood in terms of neural and cognitive principles. The article proposes a neurocognitive model of ideological thinking, arguing that ideological worldviews may be manifestations of individuals’ perceptual and cognitive systems. This model makes two claims. First, there are neurocognitive antecedents to ideological thinking: the brain’s low-level neurocognitive dispositions influence its receptivity to ideological doctrines. Second, there are neurocognitive consequences to ideological engagement: strong exposure and adherence to ideological doctrines can shape perceptual and cognitive systems. This article details the neurocognitive model of ideological thinking and synthesizes the empirical evidence in support of its claims. The model postulates that there are bidirectional processes between the brain and the ideological environment, and so it can address the roles of situational and motivational factors in ideologically motivated action. This endeavor highlights that an interdisciplinary neurocognitive approach to ideologies can facilitate biologically informed accounts of the ideological brain and thus reveal who is most susceptible to extreme and authoritarian ideologies. By investigating the relationships between low-level perceptual processes and high-level ideological attitudes, we can develop a better grasp of our collective history as well as the mechanisms that may structure our political futures.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Helen Feigin ◽  
Shira Baror ◽  
Moshe Bar ◽  
Adam Zaidel

AbstractPerceptual decisions are biased by recent perceptual history—a phenomenon termed 'serial dependence.' Here, we investigated what aspects of perceptual decisions lead to serial dependence, and disambiguated the influences of low-level sensory information, prior choices and motor actions. Participants discriminated whether a brief visual stimulus lay to left/right of the screen center. Following a series of biased ‘prior’ location discriminations, subsequent ‘test’ location discriminations were biased toward the prior choices, even when these were reported via different motor actions (using different keys), and when the prior and test stimuli differed in color. By contrast, prior discriminations about an irrelevant stimulus feature (color) did not substantially influence subsequent location discriminations, even though these were reported via the same motor actions. Additionally, when color (not location) was discriminated, a bias in prior stimulus locations no longer influenced subsequent location discriminations. Although low-level stimuli and motor actions did not trigger serial-dependence on their own, similarity of these features across discriminations boosted the effect. These findings suggest that relevance across perceptual decisions is a key factor for serial dependence. Accordingly, serial dependence likely reflects a high-level mechanism by which the brain predicts and interprets new incoming sensory information in accordance with relevant prior choices.


2022 ◽  
Author(s):  
Meiling Yan ◽  
Tingting Zuo ◽  
Jichao Zhang ◽  
Yiyang Wang ◽  
Ying Zhu ◽  
...  

A bimodal probe, erythrosine B (EB) conjugated immunoglobulin G complex (EB/IgG), has been developed for fluorescence and synchrotron X-ray fluorescence (SXRF) imaging of dopaminergic neurons in the brain.


1989 ◽  
Vol 257 (1) ◽  
pp. H157-H161 ◽  
Author(s):  
F. M. Faraci ◽  
K. A. Kadel ◽  
D. D. Heistad

The goal of this study was to examine vascular responses of the dura mater. Microspheres were used to measure blood flow to the dura and brain in anesthetized dogs. Under control conditions, blood flow to the dura was 38 +/- 3 (SE) ml.min-1.100 g-1. Values for blood flow to the dura obtained with simultaneous injection of 15- and 50-microns microspheres were similar, which suggests that shunting of 15-microns spheres was minimal. Left atrial infusion of substance P (100 ng.kg-1.min-1) and serotonin (40 micrograms.kg-1.min-1), two agonists that have been reported to increase vascular permeability in the dura, increased blood flow to the dura two- to threefold. Adenosine (iv) produced vasodilatation in the dura. Adenosine and serotonin did not affect cerebral blood flow, but substance P increased blood flow to the brain by approximately 40%. Seizures, which produce pronounced dilatation of cerebral vessels despite activation of sympathetic nerves, produced vasoconstriction in the dura. Thus 1) the dura is perfused at a relatively high level of blood flow under normal conditions and is very responsive to vasoactive stimuli, and 2) substance P and serotonin, which have been implicated in the pathogenesis of vascular headache, produce pronounced vasodilator responses in the dura mater.


2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia P. Kurzina ◽  
Anna B. Volnova ◽  
Irina Y. Aristova ◽  
Raul R. Gainetdinov

Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.


2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.


2020 ◽  
Author(s):  
Haider Al-Tahan ◽  
Yalda Mohsenzadeh

AbstractWhile vision evokes a dense network of feedforward and feedback neural processes in the brain, visual processes are primarily modeled with feedforward hierarchical neural networks, leaving the computational role of feedback processes poorly understood. Here, we developed a generative autoencoder neural network model and adversarially trained it on a categorically diverse data set of images. We hypothesized that the feedback processes in the ventral visual pathway can be represented by reconstruction of the visual information performed by the generative model. We compared representational similarity of the activity patterns in the proposed model with temporal (magnetoencephalography) and spatial (functional magnetic resonance imaging) visual brain responses. The proposed generative model identified two segregated neural dynamics in the visual brain. A temporal hierarchy of processes transforming low level visual information into high level semantics in the feedforward sweep, and a temporally later dynamics of inverse processes reconstructing low level visual information from a high level latent representation in the feedback sweep. Our results append to previous studies on neural feedback processes by presenting a new insight into the algorithmic function and the information carried by the feedback processes in the ventral visual pathway.Author summaryIt has been shown that the ventral visual cortex consists of a dense network of regions with feedforward and feedback connections. The feedforward path processes visual inputs along a hierarchy of cortical areas that starts in early visual cortex (an area tuned to low level features e.g. edges/corners) and ends in inferior temporal cortex (an area that responds to higher level categorical contents e.g. faces/objects). Alternatively, the feedback connections modulate neuronal responses in this hierarchy by broadcasting information from higher to lower areas. In recent years, deep neural network models which are trained on object recognition tasks achieved human-level performance and showed similar activation patterns to the visual brain. In this work, we developed a generative neural network model that consists of encoding and decoding sub-networks. By comparing this computational model with the human brain temporal (magnetoencephalography) and spatial (functional magnetic resonance imaging) response patterns, we found that the encoder processes resemble the brain feedforward processing dynamics and the decoder shares similarity with the brain feedback processing dynamics. These results provide an algorithmic insight into the spatiotemporal dynamics of feedforward and feedback processes in biological vision.


2011 ◽  
Vol 8 (1) ◽  
pp. 509-518
Author(s):  
Baghdad Science Journal

Forty one isolates of genus Proteus were collected from 140 clinical specimens such as urine, stool, wound, burn, and ear swabs from patients of both sex. These isolates were identified to three Proteus spp. P. mirabilis, P. vulgaris and P. penneri .The ability of these bacteria to produce L-asparaginase II by using semi quantitative and quantitative methods was determined. P. vulgaris Pv.U.92 was distinguished for high level of L-asparaginase II production with specific activity 1.97 U/mg. Optimum conditions for enzyme production were determined; D medium with 0.3% of L-asparagine at pH 7.5 with temperature degree 35°C for incubation. Ultrasonication was used to destroy the P. vulgaris Pv.U.92 cells then ASNase II was extracted and purified throughout several purification steps including precipitation with (NH4)2SO4(60-80%), DEAE-cellulose ion exchanger chromatography followed by Sephacryl S-300 filtration. The specific activity was 155.6 U/ mg and the purification fold was 27.3 with 10.4% yield.


2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Laurence Vaivre-Douret

This study covers the interesting field of the development in gifted children which is often neglected in pediatrics because psychomotor development data are still rare, since “gifted” children are generally noticed towards the end of their primary schooling by IQ measurement. Developmental studies have shown the evidence from several fields that children identified as “high-level potentialities” or “intellectually gifted” develop sensory, locomotor, neuropsychological, and language skills earlier than typically expected. The hypothesis is offered that the earlier development originates from biological processes affecting the physical development of the brain and in turn even intellectual abilities are developed earlier, potentially allowing for advanced development. Further it is discussed how these developmental advances interact with the social environment and in certain circumstances may entail increased risk for developing socioemotional difficulties and learning disabilities that often go unaddressed due to the masking by the advance intellectual abilities.


2015 ◽  
Vol 370 (1663) ◽  
pp. 20140062 ◽  
Author(s):  
Jean-Jacques Hublin ◽  
Simon Neubauer ◽  
Philipp Gunz

A high level of encephalization is critical to the human adaptive niche and emerged among hominins over the course of the past 2 Myr. Evolving larger brains required important adaptive adjustments, in particular regarding energy allocation and life history. These adaptations included a relatively small brain at birth and a protracted growth of highly dependent offspring within a complex social environment. In turn, the extended period of growth and delayed maturation of the brain structures of humans contribute to their cognitive complexity. The current palaeoanthropological evidence shows that, regarding life history and brain ontogeny, the Pleistocene hominin taxa display different patterns and that one cannot simply contrast an ‘ape-model’ to a ‘human-model’. Large-brained hominins such as Upper Pleistocene Neandertals have evolved along their own evolutionary pathway and can be distinguished from modern humans in terms of growth pattern and brain development. The life-history pattern and brain ontogeny of extant humans emerged only recently in the course of human evolution.


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