scholarly journals Multiplexed proteomics and imaging of resolving and lethal SARS-CoV-2 infection in the lung

2020 ◽  
Author(s):  
Marian Kalocsay ◽  
Zoltan Maliga ◽  
Ajit J. Nirmal ◽  
Robyn J. Eisert ◽  
Gary A. Bradshaw ◽  
...  
Keyword(s):  
Immune System ◽  
Normal Tissue ◽  
Molecular Level ◽  
Rhesus Macaques ◽  
Primary Site ◽  
Disease Response ◽  
New Methods ◽  
Combined Use ◽  
Multiplexed Imaging ◽  
Tissue Specimens

ABSTRACTNormal tissue physiology and repair depends on communication with the immune system. Understanding this communication at the molecular level in intact tissue requires new methods. The consequences of SARS-CoV-2 infection, which can result in acute respiratory distress, thrombosis and death, has been studied primarily in accessible liquid specimens such as blood, sputum and bronchoalveolar lavage, all of which are peripheral to the primary site of infection in the lung. Here, we describe the combined use of multiplexed deep proteomics with multiplexed imaging to profile infection and its sequelae directly in fixed lung tissue specimens obtained from necropsy of infected animals and autopsy of human decedents. We characterize multiple steps in disease response from cytokine accumulation and protein phosphorylation to activation of receptors, changes in signaling pathways, and crosslinking of fibrin to form clots. Our data reveal significant differences between naturally resolving SARS-CoV-2 infection in rhesus macaques and lethal COVID-19 in humans. The approach we describe is broadly applicable to other tissues and diseases.SummaryProteomics of infected tissue reveals differences in inflammatory and thrombotic responses between resolving and lethal COVID-19.

Immunomodulatory Effect of “Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy” to Cure or Prevent Hospital Acquired (Nosocomial) Infections due to Clostridium difficile (C. diff), other Pathogenic Bacteria, and Autoimmune Diseases

2018 ◽  
Vol 11 (1) ◽  
pp. 3937-3949
Author(s):  
Malireddy S Reddy
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Pathogenic Bacteria ◽  
Molecular Level ◽  
Host Immune System ◽  
Hospital Acquired Infections ◽  
The World ◽  
Probiotic Strains ◽  
The Individual ◽  
Hospital Acquired

The worldwide popularity of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to treat or prevent the hospital acquired infections (nosocomial infections) arose a great interest in the medical community around the world (Reddy and Reddy, 2016; 2017). The following questions were raised on this subject: Does Multiple Mixed Strain Probiotics directly inhibit the pathogenic bacteria (C. diff) in the gastrointestinal tract or indirectly through modulation of the host immune system or both? To be more specific, what is the exact and/or hypothetical mechanism at molecular level behind the breakthrough discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy?  To answer these questions, the specific immunomodulation regulatory functions of the individual Probiotic strains (on host) have beenresearched, investigated andoutlined in this article.  A detailed explanation(s) and hypotheses have been proposed outlining the possible cumulativedirect bacteriological and indirect immunomodulatory effects (at the molecular level) of the Multiple Mixed Strain Probiotics used in Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy to successfully treat C. diff infection.  A detailed scientific and research attempts were made to correlate the Probiotic induced immune activities in relation to the reduction of the symptoms associated with the hospital acquired Clostridium difficile infection during and after the Multiple Mixed Strain Probioitc Therapy.  Results of the clinical trials, microbiological tests on feces, and the clinical blood tests significantly revealed that the reasons for the success of Dr. Reddy’s Multiple Mixed Strain Probiotic Therapy are multifold. Presumably, it is predominantly due to the immunomodulatory effect they have exerted on the host immune system along with the direct inhibition of C. diff bacteria by multiple Probiotics, due to the production of bacteriocins, lactic acid and nutritional competency.In addition, the size of the individual cells of the Probiotic strains in the Multiple Mixed Strain Probiotics and their significant effect on immunomodulation has been thoroughly discussed. Results clearly proved that if Probiotics are absent in the GI tract during C. diff infection, the chances of patient survival is zero.  This is because of the excess immune stimulation and incurable damage to the epithelial cell barrier of the gastrointestinal tract caused by C. diff bacteria.  The results also revealed, without any doubt, as of to-datethe latest discovery of Dr. M.S. Reddy’s Multiple Mixed Strain Probiotic Therapy is the best way to cure the deadly hospital acquired infections affecting millions of people around the world, with high degree of mortality.  This has been attested by several practicng medical professionals and scientists around the world (Reddy and Reddy, 2017).

scholarly journals Sex-Specific Differences in Glioblastoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1783
Author(s):  
Anna Carrano ◽  
Juan Jose Juarez ◽  
Diego Incontri ◽  
Antonio Ibarra ◽  
Hugo Guerrero Cazares
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Molecular Level ◽  
Deep Understanding ◽  
Protective Role ◽  
Men And Women ◽  
Individualized Approach ◽  
Male Patients ◽  
Outcome Differences

Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has the worst outcome, well-established differences between men and women are limited to incidence and outcome. Little is known about sex differences in GBM at the disease phenotype and genetical/molecular level. This review focuses on a deep understanding of the pathophysiology of GBM, including hormones, metabolic pathways, the immune system, and molecular changes, along with differences between men and women and how these dimorphisms affect disease outcome. The information analyzed in this review shows a greater incidence and worse outcome in male patients with GBM compared with female patients. We highlight the protective role of estrogen and the upregulation of androgen receptors and testosterone having detrimental effects on GBM. Moreover, hormones and the immune system work in synergy to directly affect the GBM microenvironment. Genetic and molecular differences have also recently been identified. Specific genes and molecular pathways, either upregulated or downregulated depending on sex, could potentially directly dictate GBM outcome differences. It appears that sexual dimorphism in GBM affects patient outcome and requires an individualized approach to management considering the sex of the patient, especially in relation to differences at the molecular level.

Microscopy and Cell Biology: New Methods and New Questions

2019 ◽  
Vol 70 (1) ◽  
pp. 199-218
Author(s):  
Joshua D. Morris ◽  
Christine K. Payne
Keyword(s):  
Biological Sciences ◽  
Fluorescence Microscopy ◽  
Spatial Resolution ◽  
Cell Biology ◽  
Molecular Level ◽  
Label Free ◽  
Imaging Methods ◽  
New Methods ◽  
Multiple Imaging ◽  
Health And Disease

Understanding the cellular basis of human health and disease requires the spatial resolution of microscopy and the molecular-level details provided by spectroscopy. This review highlights imaging methods at the intersection of microscopy and spectroscopy with applications in cell biology. Imaging methods are divided into three broad categories: fluorescence microscopy, label-free approaches, and imaging tools that can be applied to multiple imaging modalities. Just as these imaging methods allow researchers to address new biological questions, progress in biological sciences will drive the development of new imaging methods. We highlight four topics in cell biology that illustrate the need for new imaging tools: nanoparticle-cell interactions, intracellular redox chemistry, neuroscience, and the increasing use of spheroids and organoids. Overall, our goal is to provide a brief overview of individual imaging methods and highlight recent advances in the use of microscopy for cell biology.

Reagentless determination of L-asparagine and L-arginine via the combined use of immobilized enzymes and an ion-selective electrode

1976 ◽  
Vol 54 (1) ◽  
pp. 62-65 ◽  
Author(s):  
That Tjien Ngo
Keyword(s):  
Immobilized Enzymes ◽  
Ion Selective Electrode ◽  
Ammonium Ion ◽  
Selective Electrode ◽  
New Methods ◽  
Potentiometric Response ◽  
Electrode Response ◽  
Combined Use ◽  
Hydrolysis Of

New methods for the determination of L-asparagine and arginine are described. Solutions containing L-asparagine were pumped through an asparaginase tube, which catalyzed the hydrolysis of L-asparagine to L-aspartic acid and ammonium ion. For L-arginine determination, solutions containing L-arginine were pumped through an arginase–urease tube. This dual enzyme tube catalyzed the conversion of L-arginine to L-ornithine, carbon dioxide, and ammonium ion. The ammonium ion concentrations in the effluent of the enzyme tubes were determined quantitatively by an ammonium-ion-selective electrode. The potentiometric response of the electrode was directly proportional to the logarithm of the concentration of L-asparagine and L-arginine in the range of 0.1–50 mM. An equation relating the electrode response and the substrate concentration is derived.

Photonic Force Microscopy: A New Tool Providing New Methods to Study Membranes at the Molecular Level

2000 ◽  
Vol 1 (2) ◽  
pp. 129-133 ◽  
Author(s):  
Arnd Pralle ◽  
Ernst-Ludwig Florin ◽  
Ernst H.K. Stelzer ◽  
J.K. Heinrich Hörber
Keyword(s):  
Molecular Level ◽  
Force Microscopy ◽  
New Methods

scholarly journals Electrodeformation of White Blood Cells Enriched with Gold Nanoparticles

2021 ◽  
Author(s):  
Nicholas G. Hallfors ◽  
Jeremy M. Teo ◽  
Peter Bertone ◽  
Chakra Joshi ◽  
Ajymurat Orozaliev ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Immune System ◽  
Blood Cells ◽  
Microelectrode Array ◽  
White Blood Cells ◽  
Valuable Insight ◽  
System Activity ◽  
Combined Use ◽  
Insight Into

The elasticity of white blood cells (WBCs) provides valuable insight into the condition of the cells themselves, the presence of some diseases, as well as immune system activity. In this work, we describe a novel process of refined control of WBCs elasticity through a combined use of gold nanoparticles (AuNPs) and the microelectrode array device. The capture and controlled deformation of gold nanoparticles enriched white blood cells in vitro are demonstrated and quantified. Gold nanoparticles enhance the effect of electrically induced deformation and make the DEP related processes more controllable.

scholarly journals Experiencing a Natural Disaster Accelerates Aging of the Immune System

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 679-679
Author(s):  
Marina Watowich ◽  
Kenneth Chiou ◽  
Michael Montague ◽  
Melween Martínez ◽  
James Higham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Natural Disasters ◽  
Natural Disaster ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Exact Test ◽  
Human Lifespan ◽  
Cell Gene Expression ◽  
The Impact

Abstract Extreme adverse events such as natural disasters can accelerate disease progression and promote chronic inflammation. These phenotypes also increase in prevalence with age, suggesting that experiencing adversity might accelerate aging of the immune system. Adversity can induce persistent gene regulatory changes which may mechanistically explain the immune similarities between aging and adversity. To test how immune system aging is accelerated following a natural disaster, we measured the impact of Hurricane Maria on peripheral blood immune cell gene expression in a population of free-ranging rhesus macaques (Macaca mulatta) from before (n=435) versus after (n=108) Hurricane Maria. Experiencing Hurricane Maria altered the expression of 260 genes (FDR<10%), which were primarily involved in the inflammatory response. There was significant overlap in these hurricane-affected and age-associated genes with 40% (n=104) being associated with both the hurricane and aging, more than double the expected amount (Fisher’s Exact Test OR=3.7, p=4.06 x 10–21). The effects of the hurricane and aging on gene expression were also significantly correlated (rho=0.23, p=1.33 x 10-84), suggesting that they alter similar molecular pathways in the immune system. Further, we found that animals that experienced the hurricane had a gene expression profile that was, on average, 1.6 years older than animals that did not experience the hurricane (the equivalent of 6–7 years in a human lifespan, p=0.003). Together, our results provide some of the first evidence that extreme natural disasters mechanistically accelerates aging in the immune system.

Rates of unacceptable variation (UV) of normal tissue constraints in patients undergoing chest wall/breast and regional nodal irradiation (RNI) in a routine clinical practice.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 67-67
Author(s):  
Jose Bazan ◽  
Dominic DiCostanzo ◽  
Lonika Majithia ◽  
Allison Marie Quick ◽  
Nilendu Gupta ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Normal Tissue ◽  
Daily Practice ◽  
Primary Site ◽  
Routine Clinical Practice ◽  
Regional Nodal Irradiation ◽  
Dose Volume ◽  
Internal Mammary ◽  
Key Variables ◽  
Practice Methods

67 Background: TheNSABP B51/RTOG 1304 clinical trial defines dose-volume constraints for targets/normal tissue receiving RNI. We sought to evaluate UV rate in normal tissue based on the NSABP B51/RTOG 1304 protocol in patients receiving chestwall/breast (CW/B) and RNI in daily practice. Methods: Treatment records of CW/B+RNI patients from 2/2012-5/2015 were studied for: CW or B radiotherapy (RT), RT type (intensity modulated [IMRT] or 3D conformal [3DCRT]), internal mammary node (IMN) inclusion, primary site boost, and nodal boost. No case is enrolled on B51/1304. Dose volume histogram (DVH) was analyzed for the rate of ≥ 1 UV for the following normal tissue constraints: Heart mean dose ≤ 5 Gy; ipsilateral lung (IL): V20 ≤ 35%, V10 ≤ 60%, V5 ≤ 70%; contralateral lung (CL) V5 ≤ 15%; contralateral breast (CB) V4.1 ≤ 5%. Logistic regression is used to test the association between UV and key variables. Results: 203 consecutive cases received CW/B+RNI (105 left, 98 right). RT was to CW in 170 (84%), B in 33 (16%), primary site boost 133 (66%), and IMN 170 (84%). 38 (19%) received IMRT and 14 (6.9%) had a nodal boost. 46 patients (22.6%) had ≥ 1 UV. 19 patients (9.4%) had ≥ 2 UV, all in IMRT patients. 2 patients (1.0%) had a heart UV at 5.2 Gy and 5.6 Gy. The most common UV was CB (n = 32, 15.7%) and IL V5 (n = 22, 10.8%). Higher UV rates are associated with use of IMRT (vs. 3DCRT): 86.8% vs. 7.9%, OR = 77.2 (95% CI 25.7-231.4, p < 0.0001); IMN irradiation: OR = 11.5 (95% CI 1.5-86.8, p = 0.02); and use of nodal boost: OR = 7.4 (95% CI 2.3-23.4, p = 0.001). The most common UVs in IMRT cases are CB (n = 27, 71%), IL V5 (n = 19, 50%), CL V5 (n = 14, 37%) and for 3DCRT are IL V20 (n = 5, 3%), CB (n = 5, 3%) and IL V5 (n = 3, 1.8%). On multivariate analysis, use of IMRT (OR = 64.7, 95% CI 20.8-201.5, p < 0.001) and use of nodal boost (OR = 5.5, 95% CI 1.1-27.1, p = 0.04) but not IMN irradiation (OR = 2.7, 95% CI 0.3-22.0, p = 0.35) were independently associated with higher UV rate. Conclusions: The rate of UV per B51/1304 criteria with 3DCRT in routine clinical practice is low (7.9%). Women treated with IMRT had a significantly higher overall UV rate and clinicians should be aware of this as they initiate treatment planning for RNI.

Methods of Electron Crystallography as Tools for Materials Analysis

2012 ◽  
Vol 186 ◽  
pp. 1-6
Author(s):  
Wolfgang Neumann ◽  
Holm Kirmse ◽  
Ines Häusler ◽  
Corinna Grosse ◽  
Peter Moeck ◽  
...  
Keyword(s):  
Electron Crystallography ◽  
Structural Investigations ◽  
Materials Analysis ◽  
New Methods ◽  
Gaas Matrix ◽  
Combined Use ◽  
Modern Methods ◽  
Orientation Determination ◽  
New Strategies

Abstract. New methods of electron crystallography, particularly modern methods of electron diffraction have opened new strategies for the structure analysis of nanostructured materials and materials systems. The possibilities and limitations of the combined use of electron crystallography methods will be demonstrated for a semi-automatic orientation determination of MnAs clusters in a GaAs matrix and structural investigations of ferecrystals.

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