scholarly journals A novel method to enhance the sensitivity of marker detection using a refined hierarchical prior of tissue similarities

2015 ◽  
Author(s):  
Shahin Mohammadi ◽  
Ananth Grama
Keyword(s):  
Immune Cells ◽  
Statistical Approach ◽  
Signal To Noise Ratio ◽  
Cell Types ◽  
Detection Methods ◽  
Control Mechanisms ◽  
Tissue Specific ◽  
Cellular Machinery ◽  
Marker Detection ◽  
Brain Tissues

Identification of biochemical processes that drive the transformation of a totipotent cell into various cell types is essential to our understanding of living systems. This complex machinery determines how tissues differ in terms of their anatomy, physiology, morphology, and, more importantly, how various cellular control mechanisms contribute to the observed similarities/ differences. Tissue-selective genes orchestrate various aspects of cellular machinery in different tissues, and are known to be implicated in a number of tissue-specific pathologies. We propose a novel statistical approach that identifies and removes the effect of universally expressed genes in groups of tissues. This allows us to better characterize tissue similarities, as well as to identify tissue-selective genes. We use our method to construct a reliable hierarchy of tissue similarities. The groupings of tissues in this hierarchy are used to specify successively refined priors for identifying tissue-selective functions and their corresponding genes in the reduced subspace. We show that our refinement process enhances the signal-to-noise ratio in the identification of markers. Using case studies of immune cells and brain tissues, we show that our approach significantly outperforms the state-of-the-art methods, both in terms of coverage and reliability of the predicted tissue-selective genes. Our statistical approach provides a general framework for enhancing the sensitivity of marker detection methods, which can be used in conjunction with other techniques. Even in cases where the number of available expression datasets is limited, we show that our marker detection method outperforms existing techniques. We present detailed validation on immune cells and brain tissues in this paper. Our approach can be applied to construct similar datasets of other human tissues as well, for identifying tissue-specific genes. We demonstrate how these tissue-selective genes enhance our understanding of differentiating biochemical features of brain tissues, shed light on how tissue-selective pathologies progress, and help us identify specific biomarkers and targets for future interventions.

scholarly journals Detectivity optimization to detect of ultraweak light fluxes with an EM-CCD as binary photon counter array

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ibtissame Khaoua ◽  
Guillaume Graciani ◽  
Andrey Kim ◽  
François Amblard
Keyword(s):  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Photon Counting ◽  
Detection Methods ◽  
Strong Nonlinearity ◽  
Wide Range ◽  
Depth Analysis ◽  
Spatially Extended ◽  
Extended Sources ◽  
Photon Counting Mode

AbstractFor a wide range of purposes, one faces the challenge to detect light from extremely faint and spatially extended sources. In such cases, detector noises dominate over the photon noise of the source, and quantum detectors in photon counting mode are generally the best option. Here, we combine a statistical model with an in-depth analysis of detector noises and calibration experiments, and we show that visible light can be detected with an electron-multiplying charge-coupled devices (EM-CCD) with a signal-to-noise ratio (SNR) of 3 for fluxes less than $$30\,{\text{photon}}\,{\text{s}}^{ - 1} \,{\text{cm}}^{ - 2}$$ 30 photon s - 1 cm - 2 . For green photons, this corresponds to 12 aW $${\text{cm}}^{ - 2}$$ cm - 2 ≈ $$9{ } \times 10^{ - 11}$$ 9 × 10 - 11 lux, i.e. 15 orders of magnitude less than typical daylight. The strong nonlinearity of the SNR with the sampling time leads to a dynamic range of detection of 4 orders of magnitude. To detect possibly varying light fluxes, we operate in conditions of maximal detectivity $${\mathcal{D}}$$ D rather than maximal SNR. Given the quantum efficiency $$QE\left( \lambda \right)$$ Q E λ of the detector, we find $${ \mathcal{D}} = 0.015\,{\text{photon}}^{ - 1} \,{\text{s}}^{1/2} \,{\text{cm}}$$ D = 0.015 photon - 1 s 1 / 2 cm , and a non-negligible sensitivity to blackbody radiation for T > 50 °C. This work should help design highly sensitive luminescence detection methods and develop experiments to explore dynamic phenomena involving ultra-weak luminescence in biology, chemistry, and material sciences.

scholarly journals Adult tissue-resident stem cells—fact or fiction?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Deepa Bhartiya
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Tissue Specific ◽  
Cardiac Tissues ◽  
Adult Tissues ◽  
Resident Stem Cells ◽  
Abundant Cytoplasm

AbstractLife-long tissue homeostasis of adult tissues is supposedly maintained by the resident stem cells. These stem cells are quiescent in nature and rarely divide to self-renew and give rise to tissue-specific “progenitors” (lineage-restricted and tissue-committed) which divide rapidly and differentiate into tissue-specific cell types. However, it has proved difficult to isolate these quiescent stem cells as a physical entity. Recent single-cell RNAseq studies on several adult tissues including ovary, prostate, and cardiac tissues have not been able to detect stem cells. Thus, it has been postulated that adult cells dedifferentiate to stem-like state to ensure regeneration and can be defined as cells capable to replace lost cells through mitosis. This idea challenges basic paradigm of development biology regarding plasticity that a cell enters point of no return once it initiates differentiation. The underlying reason for this dilemma is that we are putting stem cells and somatic cells together while processing for various studies. Stem cells and adult mature cell types are distinct entities; stem cells are quiescent, small in size, and with minimal organelles whereas the mature cells are metabolically active and have multiple organelles lying in abundant cytoplasm. As a result, they do not pellet down together when centrifuged at 100–350g. At this speed, mature cells get collected but stem cells remain buoyant and can be pelleted by centrifuging at 1000g. Thus, inability to detect stem cells in recently published single-cell RNAseq studies is because the stem cells were unknowingly discarded while processing and were never subjected to RNAseq. This needs to be kept in mind before proposing to redefine adult stem cells.

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

Weak Transient Electromagnetic Radiation Signal Detection Method Considering the New Watershed Image Segmentation Algorithm

2019 ◽  
Vol 34 (03) ◽  
pp. 2054009
Author(s):  
Wenjun Huo ◽  
Peng Chu ◽  
Kai Wang ◽  
Liangting Fu ◽  
Zhigang Niu ◽  
...  
Keyword(s):  
Electromagnetic Radiation ◽  
Cross Correlation ◽  
Detection Efficiency ◽  
Signal To Noise Ratio ◽  
Estimation Method ◽  
Detection Methods ◽  
Signal To Noise ◽  
Long Distance ◽  
Transient Electromagnetic ◽  
Noise Ratio

In order to study the detection methods of weak transient electromagnetic radiation signals, a detection algorithm integrating generalized cross-correlation and chaotic sequence prediction is proposed in this paper. Based on the dual-antenna test and cross-correlation information estimation method, the detection of aperiodic weak discharge signals under low signal-to-noise ratio is transformed into the estimation of periodic delay parameters, and the noise is reduced at the same time. The feasibility of this method is verified by simulation and experimental analysis. The results show that under the condition of low signal-to-noise ratio, the integrated method can effectively suppress the influence of 10 noise disturbances. It has a high detection probability for weak transient electromagnetic radiation signals, and needs fewer pulse accumulation times, which improves the detection efficiency and is more suitable for long-distance detection of weak electromagnetic radiation sources.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals Chimeric Maternal Cells with Tissue-Specific Antigen Expression and Morphology Are Common in Infant Tissues

2009 ◽  
Vol 12 (5) ◽  
pp. 337-346 ◽  
Author(s):  
Anne M. Stevens ◽  
Heidi M. Hermes ◽  
Meghan M. Kiefer ◽  
Joe C. Rutledge ◽  
J. Lee Nelson
Keyword(s):  
Islet Cells ◽  
Tissue Injury ◽  
Specific Antigen ◽  
Antigen Expression ◽  
Cell Types ◽  
Target Cells ◽  
Specific Cell ◽  
Tissue Specific ◽  
Renal Tubular Cells ◽  
Parenchymal Cells

Maternal microchimerism (MMc) has been purported to play a role in the pathogenesis of autoimmunity, but how a small number of foreign cells could contribute to chronic, systemic inflammation has not been explained. Reports of peripheral blood cells differentiating into tissue-specific cell types may shed light on the problem in that chimeric maternal cells could act as target cells within tissues. We investigated MMc in tissues from 7 male infants. Female cells, presumed maternal, were characterized by simultaneous immunohistochemistry and fluorescence in situ hybridization for X- and Y-chromosomes. Maternal cells constituted 0.017% to 1.9% of parenchymal cells and were found in all infants in liver, pancreas, lung, kidney, bladder, skin, and spleen. Maternal cells were differentiated: maternal hepatocytes in liver, renal tubular cells in kidney, and β-islet cells in pancreas. Maternal cells were not found in areas of tissue injury or inflammatory infiltrate. Maternal hematopoietic cells were found only in hearts from patients with neonatal lupus. Thus, differentiated maternal cells are present in multiple tissue types and occur independently of inflammation or tissue injury. Loss of tolerance to maternal parenchymal cells could lead to organ-specific “auto” inflammatory disease and elimination of maternal cells in areas of inflammation.

scholarly journals Automated analysis of filopodial length and spatially resolved protein concentration via adaptive shape tracking

2016 ◽  
Vol 27 (22) ◽  
pp. 3616-3626 ◽  
Author(s):  
Tanumoy Saha ◽  
Isabel Rathmann ◽  
Abhiyan Viplav ◽  
Sadhana Panzade ◽  
Isabell Begemann ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Growth Dynamics ◽  
Automated Analysis ◽  
Cell Types ◽  
Control Mechanisms ◽  
Spatially Resolved ◽  
Novel Approach ◽  
Associated Proteins

Filopodia are dynamic, actin-rich structures that transiently form on a variety of cell types. To understand the underlying control mechanisms requires precise monitoring of localization and concentration of individual regulatory and structural proteins as filopodia elongate and subsequently retract. Although several methods exist that analyze changes in filopodial shape, a software solution to reliably correlate growth dynamics with spatially resolved protein concentration along the filopodium independent of bending, lateral shift, or tilting is missing. Here we introduce a novel approach based on the convex-hull algorithm for parallel analysis of growth dynamics and relative spatiotemporal protein concentration along flexible filopodial protrusions. Detailed in silico tests using various geometries confirm that our technique accurately tracks growth dynamics and relative protein concentration along the filopodial length for a broad range of signal distributions. To validate our technique in living cells, we measure filopodial dynamics and quantify spatiotemporal localization of filopodia-associated proteins during the filopodial extension–retraction cycle in a variety of cell types in vitro and in vivo. Together these results show that the technique is suitable for simultaneous analysis of growth dynamics and spatiotemporal protein enrichment along filopodia. To allow readily application by other laboratories, we share source code and instructions for software handling.

scholarly journals Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study

2020 ◽  
Author(s):  
Aris I. Giotakis ◽  
Jozsef Dudas ◽  
Rudolf Glueckert ◽  
Daniel Dejaco ◽  
Julia Ingruber ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Chronic Rhinosinusitis ◽  
Immune Cells ◽  
Upper Airway ◽  
Image Cytometry ◽  
Cell Types ◽  
Epithelial Layer ◽  
Double Positive ◽  
Airway Mucosa ◽  
Single Positive

AbstractEpithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial–mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18–vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3–6 times higher compared to the control patients. In the epithelial layer, cytokeratin–vimentin-double-positive EMT cells were observed 3–5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.

Stable transfer and restricted expression of a cloned class I gene encoding a secreted transplantation-like antigen

1985 ◽  
Vol 5 (6) ◽  
pp. 1295-1300
Author(s):  
Y Barra ◽  
K Tanaka ◽  
K J Isselbacher ◽  
G Khoury ◽  
G Jay
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Class I ◽  
Regulatory Sequences ◽  
Transcriptional Enhancer ◽  
Gene Encoding ◽  
Specific Expression ◽  
Tissue Specific ◽  
Functional Studies ◽  
I Gene

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.

Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2799-2812 ◽  
Author(s):  
A. McCormick ◽  
N. Core ◽  
S. Kerridge ◽  
M.P. Scott
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Hox Genes ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Transcriptional Enhancer ◽  
Hox Proteins ◽  
Tissue Specific ◽  
Conserved Sequences

Along the anterior-posterior axis of animal embryos, the choice of cell fates, and the organization of morphogenesis, is regulated by transcription factors encoded by clustered homeotic or ‘Hox’ genes. Hox genes function in both epidermis and internal tissues by regulating the transcription of target genes in a position- and tissue-specific manner. Hox proteins can have distinct targets in different tissues; the mechanisms underlying tissue and homeotic protein specificity are unknown. Light may be shed by studying the organization of target gene enhancers. In flies, one of the target genes is teashirt (tsh), which encodes a zinc finger protein. tsh itself is a homeotic gene that controls trunk versus head development. We identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm. Sites where Antennapedia (Antp) and Ultrabithorax (Ubx) proteins bind in vitro were mapped within evolutionarily conserved sequences. Although Antp and Ubx bind to identical sites in vitro, Antp activates the tsh enhancer only in epidermis while Ubx activates the tsh enhancer in both epidermis and in somatic mesoderm. We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable. Next to the homeotic protein-binding sites are extensive conserved sequences likely to control tissue activation by different homeodomain proteins. We propose that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.

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