Gregory A. Johnson

Bio: Gregory A. Johnson is an academic researcher from Texas A&M University. The author has contributed to research in topics: Conceptus & Arginine. The author has an hindex of 32, co-authored 67 publications receiving 2895 citations. Previous affiliations of Gregory A. Johnson include Merck & Co..

Proline and hydroxyproline metabolism: implications for animal and human nutrition

Abstract: Proline plays important roles in protein synthesis and structure, metabolism (particularly the synthesis of arginine, polyamines, and glutamate via pyrroline-5-carboxylate), and nutrition, as well as wound healing, antioxidative reactions, and immune responses. On a per-gram basis, proline plus hydroxyproline are most abundant in collagen and milk proteins, and requirements of proline for whole-body protein synthesis are the greatest among all amino acids. Therefore, physiological needs for proline are particularly high during the life cycle. While most mammals (including humans and pigs) can synthesize proline from arginine and glutamine/glutamate, rates of endogenous synthesis are inadequate for neonates, birds, and fish. Thus, work with young pigs (a widely used animal model for studying infant nutrition) has shown that supplementing 0.0, 0.35, 0.7, 1.05, 1.4, and 2.1% proline to a proline-free chemically defined diet containing 0.48% arginine and 2% glutamate dose dependently improved daily growth rate and feed efficiency while reducing concentrations of urea in plasma. Additionally, maximal growth performance of chickens depended on at least 0.8% proline in the diet. Likewise, dietary supplementation with 0.07, 0.14, and 0.28% hydroxyproline (a metabolite of proline) to a plant protein-based diet enhanced weight gains of salmon. Based on its regulatory roles in cellular biochemistry, proline can be considered as a functional amino acid for mammalian, avian, and aquatic species. Further research is warranted to develop effective strategies of dietary supplementation with proline or hydroxyproline to benefit health, growth, and development of animals and humans.

Impacts of arginine nutrition on embryonic and fetal development in mammals.

Abstract: Embryonic loss and intrauterine growth restriction (IUGR) are significant problems in humans and other animals. Results from studies involving pigs and sheep have indicated that limited uterine capacity and placental insufficiency are major factors contributing to suboptimal reproduction in mammals. Our discovery of the unusual abundance of the arginine family of amino acids in porcine and ovine allantoic fluids during early gestation led to the novel hypothesis that arginine plays an important role in conceptus (embryo and extra-embryonic membranes) development. Arginine is metabolized to ornithine, proline, and nitric oxide, with each having important physiological functions. Nitric oxide is a vasodilator and angiogenic factor, whereas ornithine and proline are substrates for uterine and placental synthesis of polyamines that are key regulators of gene expression, protein synthesis, and angiogenesis. Additionally, arginine activates the mechanistic (mammalian) target of rapamycin cell signaling pathway to stimulate protein synthesis in the placenta, uterus, and fetus. Thus, dietary supplementation with 0.83 % L-arginine to gilts consuming 2 kg of a typical gestation diet between either days 14 and 28 or between days 30 and 114 of pregnancy increases the number of live-born piglets and litter birth weight. Similar results have been reported for gestating rats and ewes. In sheep, arginine also stimulates development of fetal brown adipose tissue. Furthermore, oral administration of arginine to women with IUGR has been reported to enhance fetal growth. Collectively, enhancement of uterine as well as placental growth and function through dietary arginine supplementation provides an effective solution to improving embryonic and fetal survival and growth.

Protein delivery into live cells by incubation with an endosomolytic agent

Abstract: We report that a tetramethylrhodamine-labeled dimer of the cell-penetrating peptide TAT, dfTAT, penetrates live cells by escaping from endosomes with high efficiency. By mediating endosomal leakage, dfTAT also delivers proteins into cultured cells after a simple co-incubation procedure. We achieved cytosolic delivery in several cell lines and primary cells and observed that only a relatively small amount of material remained trapped inside endosomes. Delivery did not require a binding interaction between dfTAT and a protein, multiple molecules could be delivered simultaneously, and delivery could be repeated. dfTAT-mediated delivery did not noticeably affect cell viability, cell proliferation or gene expression. dfTAT-based intracellular delivery should be useful for cell-based assays, cellular imaging applications and the ex vivo manipulation of cells.

Amino acids and gaseous signaling

Abstract: Gases, such as nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and sulfur dioxide (SO2) are known toxic pollutants in the air. However, they are now recognized as important signaling molecules synthesized in animals and humans from arginine, glycine (heme), and cysteine, respectively. At physiological levels, NO, CO, and SO2 activate guanylyl cyclase to generate cGMP which elicits a variety of responses (including relaxation of vascular smooth muscle cells, hemodynamics, neurotransmission, and cell metabolism) via cGMP-dependent protein kinases. H2S is also a crucial regulator of both neurological function and endothelium-dependent relaxation through cGMP-independent mechanisms involving stimulation of membrane KATP channels and intracellular cAMP signaling. Additionally, NO, CO, and H2S confer cytoprotective and immunomodulatory effects. Moreover, NH3 is a major product of amino acid catabolism and profoundly affects the function of neurons and the vasculature through glutamine-dependent inhibition of NO synthesis. Emerging evidence shows that amino acids are not only precursors for these endogenous gases, but are also regulators of their production in a cell-specific manner. Thus, recent advances on gaseous signaling have greatly expanded our basic knowledge of amino acid biochemistry and nutrition. These exciting discoveries will aid in the design of new nutritional and pharmacological means to prevent and treat major health problems related to developmental biology and nutrient metabolism, including intrauterine growth restriction, preterm birth, aging, neurological disorders, cancer, obesity, diabetes, and cardiovascular disease.

Amino acids: metabolism, functions, and nutrition

Abstract: Recent years have witnessed the discovery that amino acids (AA) are not only cell signaling molecules but are also regulators of gene expression and the protein phosphorylation cascade. Additionally, AA are key precursors for syntheses of hormones and low-molecular weight nitrogenous substances with each having enormous biological importance. Physiological concentrations of AA and their metabolites (e.g., nitric oxide, polyamines, glutathione, taurine, thyroid hormones, and serotonin) are required for the functions. However, elevated levels of AA and their products (e.g., ammonia, homocysteine, and asymmetric dimethylarginine) are pathogenic factors for neurological disorders, oxidative stress, and cardiovascular disease. Thus, an optimal balance among AA in the diet and circulation is crucial for whole body homeostasis. There is growing recognition that besides their role as building blocks of proteins and polypeptides, some AA regulate key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. They are called functional AA, which include arginine, cysteine, glutamine, leucine, proline, and tryptophan. Dietary supplementation with one or a mixture of these AA may be beneficial for (1) ameliorating health problems at various stages of the life cycle (e.g., fetal growth restriction, neonatal morbidity and mortality, weaning-associated intestinal dysfunction and wasting syndrome, obesity, diabetes, cardiovascular disease, the metabolic syndrome, and infertility); (2) optimizing efficiency of metabolic transformations to enhance muscle growth, milk production, egg and meat quality and athletic performance, while preventing excess fat deposition and reducing adiposity. Thus, AA have important functions in both nutrition and health.

Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases

Abstract: One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

Role of WHO.

Abstract: OVERVIEW The GRA Marketing Internship Program is offered to students who are interested in gaining valuable work experience through efforts in marketing, membership, sales, and events. Interns work directly to assist the Director of Marketing and Communications on various tasks relating to upcoming GRA events. During this internship, students will work a minimum of 10 hours a week and a maximum of 20 hours a week. Students are encouraged to earn credit for their internship, however this is a paid internship. Students interested in obtaining credit for their internship must consult their academic advisor or the intern coordinator at their academic unit.

Identifying airborne transmission as the dominant route for the spread of COVID-19.

Abstract: Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease. By analyzing the trend and mitigation measures in Wuhan, China, Italy, and New York City, from January 23 to May 9, 2020, we illustrate that the impacts of mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.

Review of evidence on health aspects of air pollution – REVIHAAP Project. Technical Report. World Health Organization Regional Office for Europe 2013

Abstract: This document presents answers to 24 questions relevant to reviewing European policies on air pollution and to addressing health aspects of these policies. The answers were developed by a large group of scientists engaged in the WHO project “Review of evidence on health aspects of air pollution – REVIHAAP”. The experts reviewed and discussed the newly accumulated scientific evidence on the adverse effects on health of air pollution, formulating science-based answers to the 24 questions. Extensive rationales for the answers, including the list of key references, are provided. The review concludes that a considerable amount of new scientific information on the adverse effects on health of particulate matter, ozone and nitrogen dioxide, observed at levels commonly present in Europe, has been published in recent years. This new evidence supports the scientific conclusions of the WHO air quality guidelines, last updated in 2005, and indicates that the effects in some cases occur at air pollution concentrations lower than those serving to establish these guidelines. It also provides scientific arguments for taking decisive actions to improve air quality and reduce the burden of disease associated with air pollution in Europe. This publication arises from the project REVIHAAP and has been co-funded by the European Union.