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Foods high in Arginine and Citrulline include melons and cucumber, peanuts, salmon, and soy. Is the EPC autocrine or paracrine in its functional role? It is critical to understand this biological unknown for planning therapeutic approaches. Patients with unstable angina and no evidence of cardiac necrosis exhibited increased cEPCs.
Systemic inflammation and recognized growth factors may play a role in peripheral mobilization of EPCs in patients with unstable anginal syndromes. In normal conditions, the vascular endothelium produces and secretes substances that modulate vascular tone and protect the vessel wall from inflammatory cell infiltration, thrombus formation, and vascular smooth muscle cell proliferation Rubanyi, Endothelial cell loss and turnover are accelerated in the presence of hemodynamic and biochemical alterations and are a prominent feature of vascular injury resulting from percutaneous coronary intervention.
Since the discovery of NO and its role in vascular biology, a main focus in vascular research has been to create novel mechanisms to use NO to combat neointimal hyperplasia. To date, numerous animal studies have restored NO production to the vasculature and have shown that this inhibits neointimal hyperplasia, improves patency rates, and is safe to the animal. This document explored the current understanding of sepsis as a cascade of events that involves the microcirculation unevenly because of a differential effect on the large and contiguous intestinal epithelium, secondary effects on cardiopulmonary blood flows and cardiac output, and the role of Nitric Oxide in the emergence of beneficial and potentially deleterious effects.
This leads to a substantial body of work on therapeutic targets, either aimed at total inhibition or selective inhibition of NO synthase, and the special role of iNOS. It is basic to understanding the metabolic and regulatory role of NO in health and disease. The systemic inflammatory response syndrome SIRS is the massive inflammatory reaction resulting from systemic mediator release that may lead to multiple organ dysfunction. I introduce an analysis of the roles of cytokines, cytokine production, and the relationship of cytokine production to the development of SIRS.
The article postulates a three-stage development of SIRS, in which stage 1 is a local production of cytokines in response to an injury or infection. Stage 3 is the massive systemic reaction where cytokines turn destructive by compromising the integrity of the capillary walls and flooding end organs. Sepsis is accompanied by intravascular coagulation with a drop in blood pressure, decreasing platelet count and dissemination of fibrin clots DIC. The stage is set with a hypercoagulable state from the prothrombotic milieu.
There are diverse effects of NO on platelets, the coagulation cascade, and protein-membrane interactions with low flow states, local and systemic inflammatory disease, oxidative stress, and hematologic disorders. It is highly complex as the distinction between the intrinsic and extrinsic pathways become blurred as a result of endothelial shear stress, distinctly different than penetrating or traumatic injury. In addition, there are other factors that come into play.
The finding that a substance, derived from vascular endothelium, that could control vascular tone and induce smooth muscle relaxation, led to the discovery of nitric oxide NO as a major physiological mediator 1 in many cell types and processes. However nitric oxide also produces some physiologically, pharmacologically, and pathologically relevant changes, lasting longer time periods, which is the main focus of this article. For example, nitric oxide is important in the development of long term potentiation a model of learning and memory , neural plasticity, and neurite outgrowth, revealing nitric oxide can induce more permanent changes in cellular and tissue reorganization.
These effects persist over longer time frames than the effects which most second messenger systems occur. Finally, the multifunctionality of GAPDH and its modification has the possibility for affecting many processes involved in the disease progression. In bone, NO plays a vital role in mechanosensation and mechanotransduction. They sense external mechanical loads on bone and produce chemical signals such as NO and prostaglandins. NO in turn has been shown to modulate the activity of both bone forming osteoblasts and bone resorbing osteoclasts.
NO is essential for load-induced bone formation in vivo. Studies using single gene deletions have shown that NO is an important cog in the wheel for bone metabolism and bone remodelling. Although eNOS isotype is widely implicated in NO production in bone, but recent studies indicate that iNOS isotype might also be involved in NO production in bone in response to mechanical loading.
An incoming immune signal initiates NO and ROS production both for tackling the pathogens and modulating the downstream immune response via complex signaling pathways. The complexity of these interactions is a reflection of involvement of redox chemistry in biological setting. In s a number of authors showed the direct evidence that macrophages made nitrite, nitrates and nitrosamines. It was also shown that NO generated by macrophages could kill leukemia cells Stuehr and Nathan, Collectively these studies along with others demonstrated the important role NO plays in immunity and lay the path for further research in understanding the role of redox molecules in immunity.
It is characterised by lesions in the vessels and accumulation of collagen in the tissues. The pathogenesis of this disease is not clear, but one of the suggestions is that the endothelium fails to produce NO upon cold stimulation. Physiologically, NO acts as a vasodilator and its deficiency has been implicated in diseases such as hypertension and atherosclerosis. Principally, three isoenzymes of NOS are present in the body to catalyse the production of NO in various anatomic locations and under various physiological conditions. Three distinct genes encode for the three types of NOS i.
Researchers at the Wyss Institute, Harvard, have developed lung-on-a-microfluid chip and shown that it mimics human lung function in response to Interleukin-2 IL-2 and mechanical strain. Decrease in availability of NO can lead to many complications like pulmonary hypertension. Some of the causes of decrease in NO have been identified as clinical hypertension, right ventricular overload which can lead to cardiac heart failure, low levels of zinc and high levels of cardiac necrosis.
Deonikar and Kavdia J. Inhaled nitric oxide NO , a mediator of vascular tone produces pulmonary vasodilatation with low pulmonary vascular resistance. The route of administration delivers NO selectively improving oxygenation. Developments in our understanding of the cellular and molecular actions of NO may help to explain the results of randomised controlled trials of inhaled NO. We learn that both forms have an important counter-balancing effect.
The converted ONOO- peroxynitrite has the most damaging effect. In addition, inflammatory cytokines, released early in sepsis, cause Proximal Tubular Epithelial Cells PTEC cytoskeletal damage and alter integrin-dependent cell-matrix adhesion. The apoptotic effects of proinflammatory stimuli are due to the expression of inducible NO synthase. The mechanisms of ARF involve both vascular and tubular factors.
An ischemic insult to the kidney will in general be the cause of the ARF. A relative increase in oxygen demand by the tubule is also a factor in renal ischemia. Calpain-mediated breakdown products of the actin-binding protein spectrin occur with renal ischemia. Calpain activity increased during hypoxia in isolated proximal tubules. An antisense oligonucleotide was shown to block the upregulation of iNOS and afford functional protection against acute renal ischemia. What about the NO donors as therapeutic targets?
There is agreement that oxygen-derived reactive species are important in renal ischemia-reperfusion I-R injury. Treatment with oxygen radical scavengers, antioxidants, and iron chelators such as superoxide dismutase, dimethylthiourea, allopurinol, and deferoxamine are protective.
L-NIL administered to animals subjected to I-R significantly decreased plasma creatinine levels to 1. Therefore, reactive nitrogen species should be considered potential therapeutic targets in the prevention and treatment of renal I-R injury.
NO functions to promote natriuresis and diuresis, contributing to adaptation to variations of dietary salt intake and maintenance of normal blood pressure. A pretreatment with nitric oxide donors or L-arginine may prevent the ischemic acute renal injury. In chronic kidney diseases, the systolic blood pressure is correlated with the plasma level of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase.
A reduced production and biological action of nitric oxide is associated with an elevation of arterial pressure, and conversely, an exaggerated activity may represent a compensatory mechanism to mitigate the hypertension. Adequate medullary tissue oxygenation, in terms of balanced oxygen supply and demand, is dependent on the maintenance of medullary perfusion by adequate cortical perfusion and also on the high rate of O2 consumption required for active electrolyte transport. The sensitivity of the medulla to hypoxic conditions results from high O2 consumption. Renal sodium transport is the main O2-consuming function of the kidney and is closely linked to renal blood flow for sodium transport, particularly in the thick ascending limbs of the loop of Henle and the S3 segments of the proximal tubules.
The medulla has been found to be the main site of production of NO in the kidney. You would do well to change your posting name. Same goes for the kiwi fruit. How do we know it will not visit damnation and ruin upon the seventh generation after the father who originally ate it? We already know it causes allergies in some people. Surely this is a portent of future calamitous times. Plus it sounds biblical and would make a great if somewhat cheesey B grade horror flick. You have very well developed powers of observation. Still, i now know how to write genera, and i know that the Spudd is another Onion.
I also see that the agrochemical industry wants to discredit Vani Hari because she threatens them by wielding the Food Babe Army. Some things will never change. Why do you so vigorously defend her? The critiques are nit picky and rather small minded. They miss the forest for the trees. She does not deserve this demonization. She is a narcissist with no shame. If this makes her a good person, then I have a presidential candidate with big hair for you who is also a good person.
She is attacked because she is a self-centered profiteer who makes money by scaring people.
This is standing up for a good cause? And you are incredibly naive to believe anything different. Yet, in her book she states: She has even complained that the air in a plane is diluted with nitrogen: Not only does she have a profound ignorance, but also the arrogance not to ask a real scientist to edit her book. They pick on a few old mistakes and nit-pick all day long to make the appearance of a tempest which is actually only as big a a teapot in a dollhouse.
Take off the tinfoil hat. The leaps of logic are not long, as the stepping stones are well laid out here. Van Hari is worthless trash but such is the sad state of America, an empire in terminal decline with an ignorant and fearful public, that cockroaches now occupy the limelight. Oh, that is so sad and mean, Captain. Please mind your manners. I think Vani Hari is one of the better human beings. Is it now a crime to question the supposed safety of specific chemicals, or to question the soundness of the regulatory apparatus that seems to be gamed by an industry with little compunction?
She is unethical, disingenuous, and stupid.
Editorial Reviews. Review. Hi, my name is Billy Wells I published two compilations ofhorror Pushing Your Book to First Place (By Dissecting Amazons Genome 1) - Kindle edition by Ron Mahon, Shahzad Anwar, Bonnie Santos. Download it. Pushing Your Book to First Place (Dissecting Amazons Genome 1) Andew's Gift Your Secess By empowering Napoleon Hill A Special Message From Judy.
And gets paid for it. Her misinformation to the gullible is immoral. They are not unflattering. These claims, while they go far to promote fearmongering about genetic engineering and to promote thte sale of her own alternative products — some of which ironically contain the same chemicals she slams in other products she does not sell — do not add to the scientific dialogue about genetically engineered crops. To pretend otherwise is to totally ignore everything that we do know about GE, which is considerable.
Both, in a negative sense. I see the industry making a concerted effort to slam Hari because she stands up to them strongly. Just take the time to read the book. Your leap is not based in any way on the book. Hari is slammed only because her woo is unscientific, and exposed as such. Every goofy point she makes is refuted scientifically in the book. But you have not read the book, so you believe what you choose to believe.
The greatest fear is that Fear Babe may be taken seriously.
What would motivate her? Why be a sock puppet for Monsanto? Oh, the anti-vaxxer is back with more sock puppet allegations. Daddy, read the book and learn something about the difference between science and woo-selling. But she is the wrong target my friends, she is minuscule. You must be logged in to post a comment.
New book dissects the scare tactics of Vani Hari. Food Babe describes the process: British farmers take to social media to defend herbicide's environmental benefits. So what else would injected mean for most people? Carefully rub it on the sprain and wrap it in a cheesecloth or a cloth bandage. And the silly thing fails to warn folk that tumeric causes contact dermatitis in some people. How can you be this thick? Some people want to be fooled all the time, it seems. SWS1 variation is based only on P.
Through genome and transcriptome sequencing analysis, we have characterized the genetic component of the visual system of three Amazonian cichlids. Genomic and PCR opsin evidence suggests that all three species have seven cone opsin genes and a rod opsin gene. This supports the idea that the common ancestor of the South American lineages had the same seven cone opsin genes found in the African cichlids, perhaps arising in the Gondwanan ancestor. Our results show that present day Amazonian species exhibit a variable complement of functional opsins with different opsin genes inactivated in different lineages.
Overall, these species exhibit a less rich palette of functional opsin genes than African cichlids Carleton This is in concordance with previous results on the Trinidadian pike Weadick et al. These results confirm that gene inactivation is common among percomorph fishes, thereby creating complex patterns of opsin evolution as adaptation to new spectral environments occur Davies et al.
This conversion event seems to have happened early in the Neotropical cichlid lineage as it is shared across Amazonian species and C. Gene conversion events can be frequent between adjacent opsin duplicates. This has been shown in primate L and M cone opsin genes where introns exhibit lower nucleotide divergence than exons Zhao et al. Furthermore, gene conversion occurring between exons has been found on several teleost lineages Owens et al. Our results suggest that the RH2A duplication was present early in the cichlid lineage prior to the breakup of Gondwana and the African — South American divergence.
This agrees with previous studies suggesting that opsin gene duplications promote visual pigment diversity in teleosts Chinen et al. Further studies on opsin genes of more divergent cichlids from India and Madagascar are needed to analyze the evolution of RH2 opsins. In the opsin gene trees, Neotropical cichlid opsins were placed as sister taxa to the African cichlid clade as expected.
There is general phylogenetic concordance of the taxonomic relationships across the opsin genes. This is in agreement with Neotropical cichlid phylogenetic studies where P. In spite of the diversity in genomic opsin complements, all species expressed the same three cone opsins: A reliance on three distinct cone opsins is consistent with previous studies that found a typical cone mosaic arrangement in A.
The expression profile of P. This agrees with the light environment of Neotropical rivers, particularly in the Amazon, that have very long wavelength transmission properties. Light transmission can vary according to the type of water white, black, and clear waters and hydrological cycles receding and rising Muntz ; Costa et al. S9 Martinez et al.
Furthermore, visual studies on Amazonian fishes including P. Because there is little short wavelength light transmission in Amazonian rivers and yellow pigments in cichlid eyes filter short wavelengths, we suggest that the aquatic environment in the Amazon basin has influenced the visual system adaptation of Neotropical cichlid retinas, inactivating short wavelength sensitive opsin genes SWS1, SWS2B, RH2B and shifting their opsin expression profile to the long wavelength palette.
Based on these studies, we estimate a spectral sensitivity for SWS2A between to nm. Finally, rods sensitivity should lie around — nm. This spectral sensitivity variation may include a significant effect from the type of chromophore A1-A2. However, since Amazonian rivers have little downwelling light below nm, these opsins would not be sensitive to the available light and therefore need not be expressed Fig. S9 Costa et al. Specimens used for our transcriptome analyses were aquarium trade juveniles raised in fluorescent light.
This could have influenced their opsin expression profile by increasing the expression of longer wavelength sensitive opsins. However, fish were at least five months old and also exhibited yellow lenses. Since changes in gene expression stabilize by around six months in African cichlids, our results suggest that either these fish were old enough to obtain the adult expression pattern, or that they do not undergo developmental shifts in expression Carleton et al.
The latter would be consistent with some species having lost the SWS1 and SWS2B opsins that are normally expressed in the larval to juvenile stages. Studies in African cichlids have found that the short and the long wavelength sensitive pigments are the most variable with shifts in peak sensitivity of 30 nm in the short, and 50 nm in the long wavelength sensitive opsins Carleton et al.
These results differ from previous studies that have found the greatest variation in opsins sensitive at both ends of the wavelength spectrum, SWS1 and LWS Hofmann et al. Since the Amazon basin exhibit a long wavelength light environment, the SWS2A gene may be the shortest wavelength gene to be expressed. In this way, the visual system may still be optimizing the shortest SWS2A and longest LWS opsins that are relevant to the long wavelength shifted environments where these fish are located.
Indeed, Muntz suggested that Amazonian fishes use mixtures of both chromophores Muntz , Consequently, the changing Amazon conditions over the last 7 Mya could have selected for maintenance of expression of some opsins and pseudogenization of others. Although we were not able to date the pseudogenization time for RH2B, it is possible that it might have been inactivated multiple times across lineages. More species need to be analyzed in order to better understand the pseudogenization process.
Yet it is interesting that in spite of opsin genes have been inactivated at different times in different South American lineages to generate the same expressed opsin set.
This suggests that this expressed gene set arose convergently in Amazonian cichlids Fig 5. Schematic representation of visual system adaptation in a phylogenetic context. Phylogenetic tree topology is based on Betancur et al Taxonomic groups present in the Amazon where visual systems have been analyzed at some level are displayed in black.
The cichlid inset denotes the opsin genes in the genome and the ones that are being expressed in the Neotropical and African lineages. Empty circles denote pseudogenes or lost genes. For simplicity, RH2A duplicates were excluded. Our results suggest that these Amazonian cichlids are adapting to their light environment through several different genetic mechanisms. These include changes in opsin gene expression, opsin gene sequence and the accumulation of pseudogenes relative to their African counterparts. This is further supported by yellow filters in their ocular media which filter short wavelengths, reducing the background scattered light common in these long wavelength transmitting waters.
The absence of short wavelength visual pigments seems to be common among the Amazonian ichthyofauna with a number of species having spectral sensitivities that are red shifted Table S2. Gene loss or pseudogenization also occur in other Amazonian taxa such as the absence of the short wavelength sensitive opsin genes in the electric eel Electrophorus electricus and non-electric catfish Traeger et al.
Furthermore, convergent opsin inactivation is common in mammals where opsin pseudogenes have arisen independently in response to changes in their behavior and ecology Zhao et al. Additionally, adaptations such as the presence of yellow filters in ocular media have been found in Amazonian fishes besides cichlids, such as the pink-tailed chalceus Characiformes: Chalceus macrolepidotus , the freshwater puffer fish Tetraodontiformes: Colomessus asellus , the freshwater stingray Myliobatiformes: Paratrygon motoro and several other siluriforms Fig.
In conclusion, we have described the opsin complement of three Amazonian cichlids using both RNA and genomic sequences. There is evidence for visual pigment evolution in this lineage with both opsin gene pseudogenization and gene conversion taking place. This might be a consequence of the long wavelength light environment in the Amazon basin.
This environment has further influenced cichlid visual system adaptation through adaptation of opsin gene expression, changes in amino acids substitution in spectral tuning sites, and yellow filters in ocular media; all traits characteristic of species living in a long wavelength environment. These traits likely arose convergently in response to environmental selection and seem to be shared among a number of Amazonian fishes. The molecular adaptive traits discussed in this study corroborates the vast body of vertebrate research where it has been shown that as animals occupy different ecological niches, their visual systems adapts through several mechanisms, enabling them to operate in these new spectral environments.
We also thank Carlos Schneider for his collaboration in collecting samples, Jessica Goodheart for advise in phylogenetic trees, and Fabio Cortesi for help with identifying gene duplications through read mapping. We thank three anonymous reviewers for providing helpful suggestions on this manuscript. National Center for Biotechnology Information , U. Author manuscript; available in PMC Mar 1. Find articles by Daniel Escobar-Camacho.
Find articles by Erica Ramos. Find articles by Cesar Martins. Find articles by Karen L. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Mol Ecol. See other articles in PMC that cite the published article. Abstract Vision is a critical sense for organismal survival with visual sensitivities strongly shaped by the environment.
RNA analysis To ensure high quality transcriptome assemblies, one specimen of each species was used for transcriptomes. Phylogenetic Trees Putative opsin sequences of the three South American cichlids were identified from genome and transcriptome assembled FASTA files by Tblastx querying with the cichlid opsin genes of Oreochromis niloticus Spady et al.
Gene Expression For estimating gene expression of each opsin, reads were mapped back to the assembled transcripts using RSEM as part of the Trinity package Haas et al. Spectral sensitivities To determine potential tuning sites we aligned South American cichlid opsin sequences of each opsin class with bovine rhodopsin GenBank. Pseudogenes divergence times Because pseudogenes were discovered in our analysis, we wanted to estimate when they emerged.
Results Opsin genomic sequences Genomes were assembled from three Amazonian cichlids including P. Table 1 Opsin gene classes across species. Open in a separate window. Phylogenetic trees Maximum likelihood trees based on these three Amazonian species as well as from C. Gene Expression Color vision in Amazonian cichlids is based mainly on the expression of three cone opsin genes: Spectral tuning The analysis of Amazonian cichlid opsin sequences revealed evidence of changes that might impact on spectral tuning.
Table 2 Summary of South American cichlids variation. Known tuning sites are based on Hunt et al. Discussion Opsin gene complements Through genome and transcriptome sequencing analysis, we have characterized the genetic component of the visual system of three Amazonian cichlids.
Opsin gene expression In spite of the diversity in genomic opsin complements, all species expressed the same three cone opsins: