Elastase Inhibitors in the Lung: Expression and Functional Relationships

1999 ◽  
pp. 69-94 ◽  
Author(s):  
Jean-Michel Sallenave ◽  
Kevin Morgan ◽  
Jack Gauldie ◽  
Noor Kalsheker
Keyword(s):  
Functional Relationships

Three-dimensional organization and functional relationships of endocytotic compartments in pig intestinal epithelial cells

1992 ◽  
Vol 50 (1) ◽  
pp. 576-577
Author(s):  
Julian P. Heath ◽  
Buford L. Nichols ◽  
László G. Kömüves
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Three Dimensional ◽  
Intestinal Epithelial ◽  
Cell Surfaces ◽  
Basal Surface ◽  
Functional Relationships

The newborn pig intestine is adapted for the rapid and efficient absorption of nutrients from colostrum. In enterocytes, colostral proteins are taken up into an apical endocytotic complex of channels that transports them to target organelles or to the basal surface for release into the circulation. The apical endocytotic complex of tubules and vesicles clearly is a major intersection in the routes taken by vesicles trafficking to and from the Golgi, lysosomes, and the apical and basolateral cell surfaces.Jejunal tissues were taken from piglets suckled for up to 6 hours and prepared for electron microscopy and immunocytochemistry as previously described.

Recent Advances towards Drug Design Targeting the Protease of 2019 novel coronavirus (2019-nCoV)

2020 ◽  
Vol 27 ◽  
Author(s):  
Sehrish Bano ◽  
Abdul Hameed ◽  
Mariya Al-Rashida ◽  
Shafia Iftikhar ◽  
Jamshed Iqbal
Keyword(s):  
Drug Design ◽  
Rna Polymerase ◽  
Drug Targets ◽  
Antiviral Agents ◽  
Structural Features ◽  
Antiviral Drugs ◽  
Rna Dependent Rna Polymerase ◽  
Mortality And Morbidity ◽  
Functional Relationships ◽  
Novel Coronavirus

Background: The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high level of mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes much time, there is a possibility to find an effective treatment from existing antiviral agents. Objective: In this case, there is a need to find out the relationship between possible drug targets and mechanism of action of antiviral drugs. This review discusses about the efforts to develop drug from known or new molecules. Methods: Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of corona virus. Certain antiviral drugs such as Remdesivir are RNA dependent RNA polymerase inhibitor. It has the ability to terminate RNA replication by inhibiting ATP. Results: It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents has been discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus. Conclusion: In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.

scholarly journals A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Annikka Polster ◽  
Lena Öhman ◽  
Julien Tap ◽  
Muriel Derrien ◽  
Boris Le Nevé ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Complex Variable ◽  
16S Rrna Gene Sequencing ◽  
Integrative Analysis ◽  
Rrna Gene ◽  
Analysis Pipeline ◽  
Host Interactions ◽  
Functional Relationships ◽  
Irritable Bowel ◽  
Host Genes

AbstractAlthough incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease.

scholarly journals ABA Metabolism and Homeostasis in Seed Dormancy and Germination

2021 ◽  
Vol 22 (10) ◽  
pp. 5069
Author(s):  
Naoto Sano ◽  
Annie Marion-Poll
Keyword(s):  
Seed Dormancy ◽  
Current Knowledge ◽  
Fine Tuning ◽  
Environmental Signals ◽  
Hormone Synthesis ◽  
Control Seed ◽  
Functional Relationships ◽  
Aba Metabolism ◽  
Natural Variations ◽  
Germinating Seeds

Abscisic acid (ABA) is a key hormone that promotes dormancy during seed development on the mother plant and after seed dispersal participates in the control of dormancy release and germination in response to environmental signals. The modulation of ABA endogenous levels is largely achieved by fine-tuning, in the different seed tissues, hormone synthesis by cleavage of carotenoid precursors and inactivation by 8′-hydroxylation. In this review, we provide an overview of the current knowledge on ABA metabolism in developing and germinating seeds; notably, how environmental signals such as light, temperature and nitrate control seed dormancy through the adjustment of hormone levels. A number of regulatory factors have been recently identified which functional relationships with major transcription factors, such as ABA INSENSITIVE3 (ABI3), ABI4 and ABI5, have an essential role in the control of seed ABA levels. The increasing importance of epigenetic mechanisms in the regulation of ABA metabolism gene expression is also described. In the last section, we give an overview of natural variations of ABA metabolism genes and their effects on seed germination, which could be useful both in future studies to better understand the regulation of ABA metabolism and to identify candidates as breeding materials for improving germination properties.

scholarly journals TAMI-07. THE IMMUNE MICROENVIRONMENT IN LOWER GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Anupam Kumar ◽  
Katharine Chen ◽  
Claudia Petritsch ◽  
Theodore Nicolaides ◽  
Mariarita Santi-Vicini ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Lower Grade ◽  
Functional Relationships

Abstract The determinants of the tumor-associated immune response in brain tumors are poorly understood. Using tumor samples from two molecularly distinct subtypes of lower grade glioma, MAPK-driven glioma with biallelic inactivation of CDKN2A (n=30) and IDH-mutant, 1p/19q-intact astrocytoma (n=29), we demonstrate qualitative and quantitative differences in the tumor-associated immune response and we investigate the molecular mechanisms involved. Histologically the MAPK-driven gliomas were comprised of pleomorphic xanthoastrocytoma (PXA) (n=11) and anaplastic PXA (n=19). Seven patients had paired samples from two sequential surgeries. Immune cell populations and their activity were determined by quantitative multiplex immunostaining and Digital Spatial Profiling and gene expression was analyzed by Nanostring. Functional studies were performed using established cell lines and two new patient-derived lines from MAPK-driven LGGs. MAPK-driven tumors exhibited an increased number of CD8+ T cells and tumor-associated microglial/macrophage (TAMs), including CD163+ TAMs, as compared to IDH-mutant astrocytoma. In contrast, IDH-mutant tumors had increased FOXP3+ immunosuppressive T regulatory cells. Transcriptional and protein level analyses in MAPK-driven tumors suggested an active cytotoxic T cell response with robust expression of granzyme B, present on 27% of CD8+ T cells, increased MHC class I expression, and altered cytokine profiles. Interestingly, MAPK-driven tumors also had increased expression of immunosuppressive molecules, including CXCR4, PD-L1, and VEGFA. Expression differences for cell surface and secreted proteins were confirmed in patient-derived tumor lines and functional relationships between altered chemokine expression and immune cell infiltration was investigated. Our data provide novel insights into the immune contexture of MAPK driven LGGs and suggest MAPK driven gliomas with biallelic inactivation of CDKN2A may be particularly vulnerable to immunotherapeutic modulation

scholarly journals Fundamental functional differences between gyri and sulci: implications for brain function, cognition, and behavior

2021 ◽  
Vol 1 (1) ◽  
pp. 23-41
Author(s):  
Xi Jiang ◽  
Tuo Zhang ◽  
Shu Zhang ◽  
Keith M Kendrick ◽  
Tianming Liu
Keyword(s):  
Brain Function ◽  
Cell Biology ◽  
Functional Anatomy ◽  
Building Blocks ◽  
Functional Differentiation ◽  
Cortical Folding ◽  
Brain Functions ◽  
Functional Relationships ◽  
Structural Architecture ◽  
And Behavior

Abstract Folding of the cerebral cortex is a prominent characteristic of mammalian brains. Alterations or deficits in cortical folding are strongly correlated with abnormal brain function, cognition, and behavior. Therefore, a precise mapping between the anatomy and function of the brain is critical to our understanding of the mechanisms of brain structural architecture in both health and diseases. Gyri and sulci, the standard nomenclature for cortical anatomy, serve as building blocks to make up complex folding patterns, providing a window to decipher cortical anatomy and its relation with brain functions. Huge efforts have been devoted to this research topic from a variety of disciplines including genetics, cell biology, anatomy, neuroimaging, and neurology, as well as involving computational approaches based on machine learning and artificial intelligence algorithms. However, despite increasing progress, our understanding of the functional anatomy of gyro-sulcal patterns is still in its infancy. In this review, we present the current state of this field and provide our perspectives of the methodologies and conclusions concerning functional differentiation between gyri and sulci, as well as the supporting information from genetic, cell biology, and brain structure research. In particular, we will further present a proposed framework for attempting to interpret the dynamic mechanisms of the functional interplay between gyri and sulci. Hopefully, this review will provide a comprehensive summary of anatomo-functional relationships in the cortical gyro-sulcal system together with a consideration of how these contribute to brain function, cognition, and behavior, as well as to mental disorders.

ISO/TS 20914:2019 – a critical commentary

2020 ◽  
Vol 58 (8) ◽  
pp. 1182-1190 ◽  
Author(s):  
Ian Farrance ◽  
Robert Frenkel ◽  
Tony Badrick
Keyword(s):  
Measurement Uncertainty ◽  
Measurement Data ◽  
International Normalized Ratio ◽  
Medical Laboratory ◽  
Uncertainty In Measurement ◽  
Medical Laboratories ◽  
Functional Relationships ◽  
Critical Commentary ◽  
Combined Uncertainty ◽  
Expression Of Uncertainty

AbstractThe long-anticipated ISO/TS 20914, Medical laboratories – Practical guidance for the estimation of measurement uncertainty, became publicly available in July 2019. This ISO document is intended as a guide for the practical application of estimating uncertainty in measurement (measurement uncertainty) in a medical laboratory. In some respects, the guide does indeed meet many of its stated objectives with numerous very detailed examples. Even though it is claimed that this ISO guide is based on the Evaluation of measurement data – Guide to the expression of uncertainty in measurement (GUM), JCGM 100:2008, it is with some concern that we believe several important statements and statistical procedures are incorrect, with others potentially misleading. The aim of this report is to highlight the major concerns which we have identified. In particular, we believe the following items require further comment: (1) The use of coefficient of variation and its potential for misuse requires clarification, (2) pooled variance and measurement uncertainty across changes in measuring conditions has been oversimplified and is potentially misleading, (3) uncertainty in the results of estimated glomerular filtration rate (eGFR) do not include all known uncertainties, (4) the international normalized ratio (INR) calculation is incorrect, (5) the treatment of bias uncertainty is considered problematic, (6) the rules for evaluating combined uncertainty in functional relationships are incomplete, and (7) specific concerns with some individual statements.

scholarly journals Petrographic and Geotechnical Characteristics of Carbonate Aggregates from Poland and Their Correlation with the Design of Road Surface Structures

Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 2034
Author(s):  
Jerzy Trzciński ◽  
Emilia Wójcik ◽  
Mateusz Marszałek ◽  
Paweł Łukaszewski ◽  
Marek Krajewski ◽  
...  
Keyword(s):  
Road Surface ◽  
Surface Structures ◽  
Engineering Properties ◽  
Geological Engineering ◽  
Functional Relationships ◽  
Road Design ◽  
Geotechnical Characteristics ◽  
Design Calculations ◽  
Building Engineering ◽  
Design And Construction

The paper presents the basic problem related with practical application of carbonate rocks in construction: are carbonate aggregates produced from such rocks favorable for building engineering, particularly for road design and construction? To resolve this problem, (1) the geological-engineering properties of aggregates are presented, (2) the correlation between petrographic and engineering parameters is shown, and (3) a strict correlation between the geological-engineering properties and the freezing-thawing and crushing resistance is recognized. This knowledge has allowed to assess the usefulness of asphalt concrete (AC) made from dolomite and limestone aggregates in the design and construction of road surface structures. The petrography was characterized using optical microscopy and scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscope (EDS). Engineering properties were determined in accordance with European and Polish norms and guidelines. Statistical and design calculations were performed using dedicated software. The petrographic properties, and selected physical and mechanical parameters of the aggregates, were tested to show their influence on the freezing–thawing and crushing resistance. Strong functional relationships between the water adsorption, and the freezing–thawing and crushing resistance have been observed. Aggregate strength decreased after saturation with increasing concentrations of salt solutions. Calculations of AC fatigue durability and deformation allow for reducing the thickness of the road surface structure by about 20% in comparison to normative solutions. This conclusion has impact on the economy of road design and construction, and allows for a rational utilization of rock resources, which contributes to sustainable development of the construction industry.

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