My road to Damascus: how I converted to the prohormone theory and the proprotein convertases

2012 ◽  
Vol 90 (6) ◽  
pp. 750-768 ◽  
Author(s):  
Michel Chrétien
Keyword(s):  
Clinical Skills ◽  
Plasma Cholesterol ◽  
Matrix Proteins ◽  
Activation Mechanism ◽  
Biological Functions ◽  
Proprotein Convertases ◽  
Wide Range ◽  
Viral Glycoproteins ◽  
Health And Disease ◽  
Reduce Plasma Cholesterol

My desire as a young endocrinologist to improve my clinical skills through a better knowledge of hormone chemistry led me to serendipitous discoveries and unexpected horizons. The first discovery, published in 1967, revealed that peptide hormones are derived from endoproteolytic cleavages of larger precursor polypeptides. It was the foundation of the prohormone theory. Initially thought to apply to a few hormones, the theory rapidly extended to many proteins, including neuropeptides, neurotrophins, growth and transcription factors, receptors, extracellular matrix proteins, bacterial toxins, and viral glycoproteins. Its endoproteolytic activation mechanism has become a fundamental cellular process, affecting many biological functions. It implied the existence of specific endoproteolytic enzymes. These proprotein convertases were discovered in 1990. They have been shown to play a wide range of important roles in health and disease. They have opened up novel therapeutic avenues. Inactivation of PCSK9 to reduce plasma cholesterol is currently the most promising. To make this good thing even better, I recently discovered in a French Canadian family a potent PCSK9 (Gln152His) mutation that significantly lowers plasma cholesterol and should confer cardiovascular longevity. The discovery helped me to complete the loop: “From the bedside to the bench and back to the bedside.”

scholarly journals Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation

2021 ◽  
Vol 22 (14) ◽  
pp. 7281
Author(s):  
Benoit R. Gauthier ◽  
Valentine Comaills
Keyword(s):  
Nuclear Envelope ◽  
Clinical Symptoms ◽  
Genome Instability ◽  
Chromosomal Rearrangements ◽  
Wide Range ◽  
Complex Chromosomal Rearrangements ◽  
Health And Disease ◽  
Dna Release ◽  
Sting Pathway ◽  
Eukaryote Genome

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals The mutational landscape of human olfactory G protein-coupled receptors

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ramón Cierco Jimenez ◽  
Nil Casajuana-Martin ◽  
Adrián García-Recio ◽  
Lidia Alcántara ◽  
Leonardo Pardo ◽  
...  
Keyword(s):  
G Protein ◽  
Olfactory Receptors ◽  
Activation Mechanism ◽  
Gene Repertoire ◽  
Structural Level ◽  
Ongoing Research ◽  
Wide Range ◽  
Natural Variants ◽  
The Impact ◽  
G Protein Coupled

Abstract Background Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain. Results OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset. Conclusion We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population.

Why Oral Medicine is an exemplary choice for specialty? A Comprehensive Review

2021 ◽  
Author(s):  
Shibani Sahni
Keyword(s):  
Clinical Skills ◽  
Systemic Disease ◽  
Specialty Training ◽  
Oral Medicine ◽  
New Techniques ◽  
Oral Manifestation ◽  
Complex Patients ◽  
Wide Range ◽  
Future Direction ◽  
Definition Of

The purpose of this article was to describe a narrative review of the literature for understanding the reasons behind Oral Medicine gaining popularity as a choice for post graduate specialty training. Oral Medicine is the intersection of medicine and dentistry, and the clinicians are responsible for the management of oral mucosal disease, salivary gland dysfunction and oral manifestation of systemic disease, and facial pain in the definition of oral medicine and hence having a wide range of responsibilities. Breadth of knowledge on medically complex patients for example, rheumatologic, cardiovascular, cancer, endocrine, immuno-deficiency patients is required, which makes it an extremely interesting specialty and enables the clinicians to provide interdisciplinary care to the patients. It is important for dental education to foster new techniques in learning and preparing the students for clinical skills prior to patient care. The scope of impact of Oral Medicine has increased over the years, leading to it gaining popularity amongst dentists to take it up as a specialty training. The future direction of the study will be to understand how to enhance the research, clinical practice, and education for Oral Medicine.

scholarly journals Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species

2021 ◽  
Vol 17 (2) ◽  
pp. e1008767
Author(s):  
Zutan Li ◽  
Hangjin Jiang ◽  
Lingpeng Kong ◽  
Yuanyuan Chen ◽  
Kun Lang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Prediction Accuracy ◽  
Cross Validation ◽  
Biological Processes ◽  
Biological Functions ◽  
Learning Framework ◽  
Wide Range ◽  
Genomic Scale ◽  
Downstream Gene Expression ◽  
Fold Cross Validation

N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA’s biological functions. However, the existing experimental techniques for detecting 6mA sites are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species: Arabidopsis thaliana, Fragaria vesca and Rosa chinensis with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.

scholarly journals JTrack: A Digital Biomarker Platform for Remote Monitoring of Daily-Life Behaviour in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Mehran Sahandi Far ◽  
Michael Stolz ◽  
Jona M. Fischer ◽  
Simon B. Eickhoff ◽  
Juergen Dukart
Keyword(s):  
Data Management ◽  
Open Source ◽  
Remote Monitoring ◽  
Daily Life ◽  
Smartphone Application ◽  
Valuable Insight ◽  
Motion Sensors ◽  
General Data Protection Regulation ◽  
Wide Range ◽  
Health And Disease

Health-related data being collected by smartphones offer a promising complementary approach to in-clinic assessments. Despite recent contributions, the trade-off between privacy, optimization, stability and research-grade data quality is not well met by existing platforms. Here we introduce the JTrack platform as a secure, reliable and extendable open-source solution for remote monitoring in daily-life and digital-phenotyping. JTrack is an open-source (released under open-source Apache 2.0 licenses) platform for remote assessment of digital biomarkers (DB) in neurological, psychiatric and other indications. JTrack is developed and maintained to comply with security, privacy and the General Data Protection Regulation (GDPR) requirements. A wide range of anonymized measurements from motion-sensors, social and physical activities and geolocation information can be collected in either active or passive modes by using JTrack Android-based smartphone application. JTrack also provides an online study management dashboard to monitor data collection across studies. To facilitate scaling, reproducibility, data management and sharing we integrated DataLad as a data management infrastructure. Smartphone-based Digital Biomarker data may provide valuable insight into daily-life behaviour in health and disease. As illustrated using sample data, JTrack provides as an easy and reliable open-source solution for collection of such information.

Characterization of proteins with Siaα2-3/6Gal-linked glycans from bovine milk and role of their glycans against influenza A virus

2018 ◽  
Vol 9 (10) ◽  
pp. 5198-5208 ◽  
Author(s):  
Hanjie Yu ◽  
Yaogang Zhong ◽  
Zhiwei Zhang ◽  
Xiawei Liu ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Bovine Milk ◽  
Milk Proteins ◽  
Biological Functions ◽  
Wide Range ◽  
Range Of Functions ◽  
Bovine Milk Proteins

The bovine milk proteins have a wide range of functions, but the role of the attached glycans in their biological functions has not been fully understood yet.

The Genetics and Genomics of Asthma

2018 ◽  
Vol 19 (1) ◽  
pp. 223-246 ◽  
Author(s):  
Saffron A.G. Willis-Owen ◽  
William O.C. Cookson ◽  
Miriam F. Moffatt
Keyword(s):  
Sequence Variation ◽  
Human Microbiome ◽  
Technological Advances ◽  
Genome Wide ◽  
A Genome ◽  
Wide Range ◽  
Health And Disease ◽  
Wide Scale ◽  
Genetics And Genomics ◽  
The Individual

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis—assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale—have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.

Sign in / Sign up

Export Citation Format

Share Document