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Biomedical subjects

Jun Li

Publications and source records attributed to Jun Li.

At least 397 records · Page 22Linked to original sources
PubMed2004

Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype.

Maple syrup urine disease (MSUD) results from mutations affecting different subunits of the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex. In this study, we identified seven novel mutations in MSUD patients from Israel. These include C219W-alpha (TGC to TGG) in the E1alpha subunit; H156Y-beta (CAT to TAT), V69G-beta (GTT to GGT), IVS 9 del[-7:-4], and 1109 ins 8bp (exon 10) in the E1beta subunit; and H391R (CAC to CGC) and S133stop (TCA to TGA) affecting the E2 subunit of the branched-chain alpha-ketoacid dehydrogenase complex. Recombinant E1 proteins carrying the C219W-alpha or H156Y-beta mutation show no catalytic activity with defective subunit assembly and reduced binding affinity for cofactor thiamin diphosphate. The mutant E1 harboring the V69G-beta substitution cannot be expressed, suggesting aberrant folding caused by this mutation. These E1 mutations are ubiquitously associated with the classic phenotype in homozygous-affected patients. The H391R substitution in the E2 subunit abolishes the key catalytic residue that functions as a general base in the acyltransfer reaction, resulting in a completely inactive E2 component. However, wild-type E1 activity is enhanced by E1 binding to this full-length mutant E2 in vitro. We propose that the augmented E1 activity is responsible for robust thiamin responsiveness in homozygous patients carrying the H391R E2 mutation and that the presence of a full-length mutant E2 is diagnostic of this MSUD phenotype. The present results offer a structural and biochemical basis for these novel mutations and will facilitate DNA-based diagnosis for MSUD in the Israeli population.

Alleles↗
PubMed2004

Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3.

Pax3 is a transcription factor that is required by pre-migratory neural crest cells, which give rise to the peripheral nervous system, melanocytes, some vascular smooth muscle, and numerous other derivatives [corrected]. Both mice and humans with Pax3 deficiency exhibit neural crest-related developmental defects [corrected]. Pax3 is also expressed in the dorsal neural tube, and by myogenic progenitors in the presomitic mesoderm and the hypaxial somites. Molecular pathways that regulate Pax3 expression in the roof plate probably represent early upstream signals in neural crest induction. We have identified an enhancer region in the Pax3 genomic locus that is sufficient to recapitulate expression in neural crest precursors in transgenic mice. We show that Tead2, a member of the Tead box family of transcription factors, binds to a neural crest enhancer and activates Pax3 expression. Tead2, and its co-activator YAP65, are co-expressed with Pax3 in the dorsal neural tube, and mutation of the Tead2 binding site in the context of Pax3 transgenic constructs abolishes neural expression. In addition, a Tead2-Engrailed fusion protein is able to repress retinoic acid-induced Pax3 expression in P19 cells and in vivo. These results suggest that Tead2 is an endogenous activator of Pax3 in neural crest.

Animals↗
PubMed2004

Slow desorption mechanisms of volatile organic chemical mixtures in soil and sediment micropores.

Desorption profiles of trichloroethylene (TCE), tetrachloroethylene (PCE), and a TCE-PCE mixture were measured for three natural solids and four zeolites. Initial sorbed mass (Mi) in slow desorbing sites of natural solids and in micropores of zeolites were obtained from desorption profiles. In natural solids, Mi increases with recalcitrant organic matter content. In zeolites, Mi generally increases with decreasing micropore width and increasing micropore hydrophobicity, but the effect of hydrophobicity is stronger. In both natural solids and zeolites, competition between TCE and PCE causes Mi for each sorbate in the mixture to be less than or similar to that for each sorbate alone. Zeolite results indicate that micropore width affects this competition more than micropore hydrophobicity for the solids examined. Desorption in all solids was simulated with the radial diffusion model, either alone or coupled with the advection-dispersion equation when necessary; diffusion rate constants (D/R2) were obtained. In natural solids, mean values of D/R2 increase with decreasing recalcitrant organic matter content. In zeolites, values of D/R2 generally increase with increasing micropore width, while they are a weak function of hydrophobicity. In both natural solids and zeolites, competition between TCE and PCE causes D/R2 for each sorbate in the mixture to generally be larger than that for each sorbate alone. Zeolite results indicate that the effects of competition on D/R2 generally decrease with decreasing micropore width for the solids examined; a trend with micropore hydrophobicity is not apparent. For the three natural solids and four zeolites examined in this study, the similar effects of competition between TCE and PCE on values of Mi and D/R2 and the overlapping range of D/R2 values support the hypothesis that diffusion through hydrophobic micropores affects and may control slow mass transfer processes in the recalcitrant organic matter of natural solids. These results contribute to the fundamental understanding of slow mass transfer processes in natural solids, and they indicate that characterization of micropore width and polarity may be necessary to predict organic chemical transport and fate.

Adsorption↗
PubMed2004

Determination of genes involved in the early process of embryonic implantation in rhesus monkey (Macaca mulatta) by suppression subtractive hybridization.

Embryonic implantation is a temporally and spatially restricted process that involves a precise cross talk between the embryo and the receptive maternal endometrium. Underlying the complex changes in the uterus during implantation is the alteration in gene expression pattern, which is not fully understood for the primates. In the present study, suppression subtractive hybridization (SSH) was performed to screen genes that were differentially expressed in the implantation site of the pregnant rhesus monkey, and a subtractive cDNA library was constructed. Furthermore, with dot blot analysis, reverse Northern blot analysis, and semiquantitative reverse transcription-polymerase chain reaction, 76 of 376 clones randomly selected from the library were proven to be differentially expressed in the implantation site. With DNA sequencing and BLAST analysis against the GenBank/EMBL database, it was demonstrated that the cDNA fragments carried by 73 clones shared high homology with 31 human genes. Among them, 15 positive clones represented the S100A10 gene and 10 positive ones corresponded with the secreted frizzled-related protein 4 gene. The other two clones shared homology with one human EST. There was one clone homologous to a human DNA sequence, which indicated that it might be a novel gene. To our knowledge, this is the first report to determine genes involved in the early implantation stage in the rhesus monkey with high throughput technology.

Animals↗
PubMed2004

Phenotypic clustering in MPZ mutations.

Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily with single extracellular, transmembrane and cytoplasmic domains. Homotypic interactions between extracellular domains of MPZ adhere adjacent myelin wraps to each other. MPZ is also necessary for myelin compaction since mice which lack MPZ develop severe dysmyelinating neuropathies in which compaction is dramatically disrupted. MPZ mutations in humans cause the inherited demyelinating neuropathy CMT1B. Some mutations cause the severe neuropathies of infancy designated as Dejerine-Sottas disease, while others cause a 'classical' Charcot-Marie-Tooth (CMT) disease Type 1B (CMT1B) phenotype with normal early milestones but development of disability during the first two decades of life. Still other mutations cause a neuropathy that presents in adults, with normal nerve conduction velocities, designated as a 'CMT2' form of CMT1B. To correlate the phenotype of patients with MPZ mutations with their genotype, we identified and evaluated 13 patients from 12 different families with eight different MPZ mutations. In addition, we re-analysed the clinical data from 64 cases of CMT1B from the literature. Contrary to our expectations, we found that most patients presented with either an early onset neuropathy with signs and symptoms prior to the onset of walking or a late onset neuropathy with signs and symptoms at around age 40 years. Only occasional patients presented with a 'classical' CMT phenotype. Correlation of specific MPZ mutations with their phenotypes demonstrated that addition of either a charged amino acid or altering a cysteine residue in the extracellular domain caused a severe early onset neuropathy. Severe neuropathy was also caused by truncation of the cytoplasmic domain or alteration of an evolutionarily conserved amino acid. Taken together, these data suggest that early onset neuropathy is caused by MPZ mutations that significantly disrupt the tertiary structure of MPZ and thus interfere with MPZ-mediated adhesion and myelin compaction. In contrast, late onset neuropathy is caused by mutations that more subtly alter myelin structure and which probably disrupt Schwann cell-axonal interactions.

Adult↗
PubMed2004

Developing a convenient large animal model for gene transfer to salivary glands in vivo.

BACKGROUND: Localized gene transfer to salivary glands has great potential for the treatment of salivary gland, systemic, and oral diseases. The minipig parotid gland, given its volume and morphological similarities to the human parotid gland, may be useful as a large animal model for pre-clinical gene transfer experiments. The purpose of this study was to perform an initial assessment of the efficacy and safety of adenoviral-vector-mediated gene transfer to parotid glands of miniature pigs. METHODS: AdCMVluc, a recombinant type 5 adenoviral (rAd5) vector containing a luciferase reporter gene, was administered to miniature pig parotid glands by intraductal cannulation. Five regions of gland tissue were obtained to measure the distribution of luciferase activity. The effects of time, viral dose, infusate buffer volume, and gland anatomical region on transgene expression were determined. Detailed serum chemistry and hematological analyses were performed. In addition, AdCMVlacZ, a similar rAd5 vector encoding beta-galactosidase, was also delivered to determine the parotid gland cell types transduced. RESULTS: Luciferase assays indicated that gene transfer to miniature pig salivary glands could be readily accomplished using rAd5 vectors. Highest transgene expression was found in the center of glands, which was > posterior > inferior > anterior > superior tissue regions. Expression was maximal on day 2 and declined to background by day 14, and observed in both acinar and ductal cells. Several serum chemistry and hematology parameters were transiently changed following rAd5 administration. CONCLUSIONS: Transgene expression by, and inflammatory response to, rAd5 vectors in minipig parotid glands are similar to results seen earlier in rodent studies. This suggests that results of salivary gland gene transfer from rodent studies can be extended to a larger animal model, and supports the value of using minipigs for pre-clinical applications of gene transfer to these tissues. Published in 2004 by John Wiley & Sons, Ltd.

Adenoviridae↗
PubMed2004

Significant differences in proton trimethyl ammonium signals between human gastrocnemius and soleus muscle.

PURPOSE: To study the apparent heterogeneous characteristics of trimethyl ammonium (TMA) in healthy human muscles at rest, and to illustrate the importance of establishing the baseline characteristics of proton metabolites in muscles with a West Nile patient. MATERIALS AND METHODS: Point-resolved spectroscopy (PRESS) magnetic resonance spectroscopy imaging (MRSI) with lipid suppression and optional outer-volume presaturation were used to acquire 1H spectra of human muscles at rest at 1.5 Tesla. A total of 28 subjects (27 normal volunteers and 1 patient with West Nile disease) between the ages of 22 and 76 participated in the study. RESULTS: The apparent T2 values of TMA for soleus and gastrocnemius muscles in normal volunteers are 180 +/- 50 and 80 +/- 20 msec, respectively. This difference has profound effects on the apparent spectral pattern of 1H metabolites. The TMA/total creatine (tCr) spectral pattern of the soleus muscle of a West Nile patient resembles that of gastrocnemius muscle of healthy volunteers. CONCLUSION: There are significant differences in the apparent T2 values of TMA between healthy soleus and gastrocnemius muscles at rest. It is important to establish the baseline characteristics of proton metabolites before clinical or physiological studies can be performed.

Adult↗
PubMed2004

Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) provides a human model to investigate the role of PMP22 in myelinated peripheral nerve, since the disease is caused by a deletion of one of the two PMP22 alleles. To systematically characterize the phenotype of HNPP, we prospectively evaluated the clinical features and electrophysiological findings in 17 genetically confirmed patients, 7 men and 10 women, ranging in age from 9 to 66 years (mean, 41 +/- 13). Fifteen symptomatic patients presented with episodes of transient focal weakness or sensory loss that were usually related to particular activities causing nerve compression, including stretching or minor repetitive focal trauma. No patient sought medical attention for symptoms of a symmetric polyneuropathy. Neurological examinations were either normal or mildly abnormal. Neither focal slowing of nerve conduction studies, nor reduction in compound muscle action potential (CMAP) or sensory nerve action potential (SNAP) amplitudes consistently predicted the site of symptoms. We conclude that the majority of patients with HNPP present with transient, recurrent, focal symptoms of weakness or sensory loss in the distribution of individual nerves or plexus, and that a diffuse symmetric sensorimotor polyneuropathy is an unusual presentation of HNPP. These studies suggest that the function of PMP22, at least in part, is to stabilize myelin so that it will be protected from injuries resulting from repetitive, minor trauma.

Adolescent↗
PubMed2004

Relationship between the expression of connexin43 and bystander effect of suicide gene therapy in ovarian cancer.

The relationship of connexin43 (Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro was explored and the effect of all-trans retinoic acid (RA) on the expression of Cx43 and bystander effect investigated. The Cx43 expression was detected by flowcytometry, Western blot, and immunofluorescence in two ovarian tumor cell lines OVCAR3, CaOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than that in CaOV3 (P<0.05). The expression of Cx43 was detected in OVCAR3 by flowcytometry and Western blot, but it could not be detected in CaOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluoresence staining showed that Cx43 protein of OVCAR3 was located on membrane surface, whereas CaOV3 in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be enhanced by RA in ovarian cancer.

Antiviral Agents↗
PubMed2004

The expression of hypoxia inducible factor 1-alpha in lung cancer and its correlation with P53 and VEGF.

To investigate the expression of hypoxia inducible factor 1-alpha (HIF-1alpha) and its correlation with P53 and vascular endothelial growth factor (VEGF), immunohistochemical technique was employed to detect the protein expressions of HIF-1alpha, P53 and VEGF in specimens from 57 patients with lung cancer. The results indicated that the total positive proportion of HIF-1alpha expression was 63% and the HIF-1alpha expression was more frequent in bronchiole-alveolar carcinoma (86%) than in other lung cancer. There was a strong association of HIF-1alpha with VEGF and P53 protein expressions. It is concluded that HIF-1alpha overexpression is a common event in lung cancer, which may be related to the up-regulation of the angiogenic factor VEGF and oncogene mutant P53 protein.

Adenocarcinoma↗
PubMed2004

Are angiotensin receptor blockers neuroprotective?

Stroke is one of the leading causes of invalidism and death in the industrialized world. Among others, the renin- angiotensin system (RAS) has been implicated in the pathogenesis and outcome of ischemic events, including stroke. Angiotensin II (Ang II), the major effector peptide of the RAS, exerts most of its well-defined physiologic and pathophysiologic actions, including those on the central and peripheral nervous system, through its Ang II type 1 (AT1) receptor subtype. This receptor not only contributes to stroke-related pathologic mechanisms (eg, hypertension, atherothrombosis, and cardiac hypertrophy) but also may be involved in postischemic damage to the brain. However, it has also been demonstrated that Ang II, via its AT2 receptor subtype, accelerates neuronal tissue regeneration after injury. In this article, we review the experimental evidence supporting the notion that blockade of brain AT1 receptors can be beneficial with respect to stroke incidence and outcome. We further delineate how AT2 receptors could be involved in neuronal regeneration following brain injury, such as stroke. In doing so, we also attempt to shed some light on the mechanisms by which AT1 receptor blockers, which leave the AT2 receptor unopposed, might exert protective actions in brain ischemia.

Angiotensin Receptor Antagonists↗
PubMed2004

Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery.

BACKGROUND: The development of fibromuscular intimal hyperplasia and subsequent graft failure remains an urgent problem in cardiac surgery. Transforming growth factor-beta1 (TGF-beta1) is involved in the pathogenesis of arteriosclerosis through induction of extracellular matrix proteins. We tested the hypothesis that intimal hyperplasia is already present in human saphenous veins and left internal mammary arteries before coronary artery bypass surgery and is associated with an increased expression of TGF-beta1. METHODS: Forty-six segments of saphenous veins and 27 of left internal mammary arteries were collected from 50 patients undergoing coronary artery bypass surgery. Morphometric analysis was performed by microscopic computer analysis. Immunohistochemistry was performed with antibodies directed against TGF-beta1, its latent binding protein (LTBP-1) and its type 2 receptor (RII). RESULTS: The incidence of intimal hyperplasia was significantly higher in saphenous veins (67.4%) than in mammary arteries (29.6%; p < 0.05). Saphenous veins and mammary arteries with intimal hyperplasia expressed more TGF-beta1 (endothelial and intimal layers) and LTBP-1 (intimal and medial layers) when compared with corresponding vessels without hyperplasia (both groups p < 0.05). Endothelial and intimal RII expression was significantly higher in saphenous veins with intimal hyperplasia as compared with saphenous veins without hyperplasia (p < 0.05). Transforming growth factor-beta1 staining in the intima correlated with the presence of an intimal hyperplasia in saphenous veins (rho = 0.317) and mammary arteries (rho = 0.428). CONCLUSIONS: Local TGF-beta1 expression is associated with the presence of intimal hyperplasia in the examined vessels. Preexisting intimal hyperplasia is more prevalent and serious in saphenous veins than in left internal mammary arteries, giving further explanation to the superior long-term results of left internal mammary grafts.

Aged↗
PubMed2004

Photo-crosslinkable microcapsules formed by polyelectrolyte copolymer and modified collagen for rat hepatocyte encapsulation.

New anionic polyelectrolyte tetra-copolymers with photo-crosslinkable 4-(4-methoxycinnamoyl)phenyl methacrylate monomer in addition to a HEMA-MMA-MAA ter-copolymer system were synthesized. The tetra-copolymers were used to form photo-crosslinkable microcapsules with modified collagen by complex coacervation for rat hepatocytes encapsulation. The hepatocytes were encapsulated within a two-layered membrane comprising of modified collagen as the inner core and an outer photo-crosslinkable copolymer shell. Upon photo-crosslinking of the microcapsules with UV-Vis light irradiation, the mechanical strength and chemical stability of the microcapsules, and the cellular functions of the encapsulated hepatocytes were enhanced. Particularly, the mechanical stability of the microcapsules was dramatically strengthened. The new photo-crosslinkable tetra-copolymer formulation described in this article has opened a way to the development of hepatocyte microencapsulation technology for bioartifical liver assist device.

Animals↗
PubMed2004

PPF1 inhibits programmed cell death in apical meristems of both G2 pea and transgenic Arabidopsis plants possibly by delaying cytosolic Ca2+ elevation.

PPF1 encodes a putative calcium ion carrier that affects the flowering time of transgenic Arabidopsis by modulating Ca(2+) storage capacities in chloroplasts of a plant cell. In the current work, we found that differential expression of PPF1 might affect processes of programmed cell death (PCD) since DNA fragmentation was detected in senescencing apical buds of long day-grown G2 pea (Pisum sativum L.) plants, but was not in non-senescencing short day-grown counterparts at all growth stages. An animal inhibitor of caspase-activated DNase (ICAD) homologue was detected in short day-grown plant continuously throughout the whole experiment and only in early stages of long day-grown pre-floral G2 pea apical buds. DNA fragmentation was significantly inhibited in apical meristems of transgenic Arabidopsis that over-expressed the PPF1 gene when compared to that of either wild-type control or to PPF1 (-) plants. The expression of ICAD-like protein decreased to undetectable level at 45 dpg in apical tissues of PPF1 (-) Arabidopsis, which was much earlier than that found in PPF1 (+) or wild-type controls. In epidermal cells of PPF1 (-) plants, we recorded significantly earlier calcium transient prior to PCD. We suggest that the expression of PPF1, a chloroplast localized Ca(2+) ion channel may inhibit programmed cell death in apical meristems of flowering plants by keeping a low cytoplasmic calcium content that might inhibit DNA fragmentation in plant cells.

Apoptosis↗
PubMed2004

Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays.

Enzymatic activity in the fecal droppings from the house dust mite has been postulated to contribute to the elicited allergic response. Screening dust mite extracts through 137,180 tetrapeptide fluorogenic substrates allowed for the characterization of proteolytic substrate specificity from the potential cysteine and serine proteases in the extract. The extract was further screened against a 4000 member peptide nucleic acid (PNA) encoded inhibitor library designed to target cysteine proteases using microarray detection. Affinity chromatography coupled with mass spectrometry identified Der p 1 as one of the proteases targeted by the PNA inhibitors in the dust mite lysate. A phenotypic readout of Der p 1 function in allergy progression was demonstrated by the inhibition of CD25 cleavage from T cells by dust mite extract that had been treated with the Der p 1 inhibitor identified from the PNA-encoded inhibitor library.

Amino Acid Sequence↗
PubMed2004

Real-time 3-dimensional echocardiography for quantification of the difference in left ventricular versus right ventricular stroke volume in a chronic animal model study: Improved results using C-scans for quantifying aortic regurgitation.

OBJECTIVE: The purpose of our study was to test the applicability of calculating the difference between left ventricular (LV) and right ventricular (RV) stroke volume (SV) for assessing the severity of aortic (Ao) regurgitation (AR) using a real-time 3-dimensional (3D) echocardiographic (RT3DE) imaging system. METHODS: The Ao valve was incised in 5 juvenile sheep, 6 to 10 weeks before the study, to produce AR (mean regurgitant fraction = 0.50). Simultaneous hemodynamic and RT3DE images were obtained on open-chest animals with Ao and pulmonary flows derived by Ao and pulmonary electromagnetic flowmeters balanced against each other. Four stages (baseline, volume loading, sodium nitroprusside, and angiotensin infusion) were used to produce a total of 16 different hemodynamic states. Epicardial scanning was done with a 2.5-MHz probe to sequentially record first the RV and then the LV cavities. Cavity volumes from the 3D echocardiography data were determined from angled sector planes (B-scans) and parallel cutting planes (C-scans, which are planes perpendicular to the direction of the volume interrogation). AR volumes were determined from 3D images by computing and then subtracting RV SVs from LV SVs and then these were compared with electromagnetic flowmeter-derived SV and regurgitant volumes. RESULTS: There was close correlation between RV and LV SVs of the RT3DE and electromagnetic methods (C-scans: LV, r = 0.98, standard error of the estimate [SEE] = 2.62 mL, P =.0001; RV, r = 0.89, SEE = 2.67 mL, P <.0001; and B-scans: LV, r = 0.95, SEE = 3.55 mL, P =.0001; RV, r = 0.77, SEE = 2.78 mL, P =.0003). Because of the small size of the RV in this model, the correlation was closer for C-scans than B-scans for RV SV. AR volume estimation also showed that C-scan (r = 0.93, SEE = 4.23 mL, P <.0001) had closer correlation than B-scan (r = 0.89, SEE = 4.87 mL, P <.0001). However, B-scan-derived AR fraction showed closer correlation than did C-scan (r = 0.82 vs r = 0.85, respectively). CONCLUSION: In this animal model, RT3DE imaging had the ability to reliably quantify both LV (B- and C-scans) and RV SVs and to assess the severity of AR.

Animals↗
PubMed2004

Production of recombinant C5a from rainbow trout (Oncorhynchus mykiss): role in leucocyte chemotaxis and respiratory burst.

Activation of the complement system can lead to the formation of the membrane attack complex, in which the component C5 is cleaved into C5a and C5b fragments. The C5a anaphylatoxin is a very potent pro-inflammatory molecule that induces chemotaxis and respiratory burst processes in a variety of mammalian leucocytes. While C5a has been well studied in mammals, little is known about the structure and function of C5a in teleost fish or other non-mammalian species. In the present study, we have produced and purified recombinant rainbow trout C5a (rtC5a), and we have shown that it plays an important role in inducing leucocyte migration as well as in triggering the respiratory burst of peripheral blood (PBLs) and head kidney leucocytes (HKLs). When the carboxy-terminal Arg was removed from rtC5a, its ability to induce cell migration and superoxide production remained intact. Interestingly, we show that leucocytes migrating towards rtC5a attached to the plate with a well-spread circular morphology, whereas those migrating towards activated trout serum displayed more irregular and dendritic-like shapes. Our data suggest that the basic mechanisms of action of the C5a anaphylotoxin have remained conserved for more than 300 million years.

Animals↗