PubMed Health⌕ Search

Biomedical subjects

H Song

Publications and source records attributed to H Song.

At least 19 recordsLinked to original sources

Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines.

Cell migration and angiogenesis are key steps in tumor metastasis. However, the mechanism of migration regulated by vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is not completely understood. This study examined the relationship between VEGF and migration, along with the mechanism involved in the VEGF-regulated migration of human gastric cancer cells. The level of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the malignant progression of tumors. Accordingly, this study examined the effect of IL-18 on the migration of cancer cells in order to identify the factors involved in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF-enhanced migration, and IL-18 increased cell migration directly through filamentous-actin polymerization and tensin downregulation. It was confirmed that rhVEGF-165 increased IL-18 production significantly. An antioxidant and an extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF-165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation of region of interest (ROI) and activated the ERK1/2 pathway. These results suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and ERK1/2 phosphorylation, which results in the increased migration of gastric cancer cells.

Actins↗

Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma.

Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant, which can stimulate T cells bearing certain T-cell receptor beta-chain variable regions, when bound to major histocompatibility complex II molecules. In vivo administration of intact superantigen in sufficient therapeutic amounts risks unwanted cytotoxicity against normal cells. In this study, we used SEA fused with CD80 transmembrane region (named as SEAtm) driven by alpha-fetoprotein (AFP) enhancer/promoter to reduce toxicity and to improve safety and efficiency in the application of SEA. We demonstrated that SEAtm by adenovirus from the AFP enhancer/promoter (AdAFPSEA) could be expressed on the surface of AFP-producing cell line Hepa1-6 instead of non-AFP-producing cell lines. Hepa1-6 infected by recombinant adenovirus stimulated proliferation of splenocytes and activated CD4(+) and CD8(+) T cells in vitro. After AdAFPSEA was injected into the subcutaneously established hepatoma in vivo, the expression of SEA was detected in tumor tissues, which subsequently induced tumor-specific cytotoxic T cells in spleen. Moreover, hepatocellular carcinoma (HCC) xenografts were suppressed by treatment with AdAFPSEA and the survival time of treated mice was prolonged. These findings suggest that membrane-expressed SEA by adenovirus from AdAFPSEA can generate stronger local and systemic antitumor responses against HCC.

Adenoviridae↗

Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population.

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. pRb controls the cell cycle and polymorphisms within it are candidates for such low penetrance susceptibility alleles, since the gene has been implicated in several human tumours, particularly breast cancer. The purpose of this study was to determine whether common variants in the RB1 gene are associated with breast cancer risk. We assessed 15 tagging single-nucleotide polymorphisms (SNPs) using a case-control study design (n< or = 4474 cases and n < or = 4560 controls). A difference in genotype frequencies was found between cases and controls for rs2854344 in intron 17 (P-trend = 0.007) and rs198580 in intron 19 (P-trend = 0.018). Carrying the minor allele of these SNPs appears to confer a protective effect on breast cancer risk (odd ratio (OR) = 0.86 (0.76-0.96) for rs2854344 and OR = 0.80 (0.66-0.96) for rs198580). However, after adjusting for multiple testing these associations were borderline with an adjusted P-trend = 0.068 for the most significant SNP (rs2854344). The RB1 gene is not known to contain any coding SNPs with allele frequencies > or = 5% but several intronic variants are in perfect linkage disequilibrium with the associated SNPs. Replication studies are needed to confirm the associations with breast cancer.

Aged↗

Elevated phosphorylation and activation of PDK-1/AKT pathway in human breast cancer.

Activation of kinases signalling pathways contributes to various malignant phenotypes in human cancers, including breast tumour. To examine the possible activation of these signalling molecules, we examined the phosphorylation status in 12 protein kinases and transcription factors in normal primary human mammary epithelial cells, telomerase-immortalised human breast epithelial cell line, and two breast cancer lines, MDA-MB-468 and MCF-7, using Kinexus phosphorylated protein screening assays. The phosphorylation of FAK, mTOR, p70S6K, and PDK-1 were elevated in both breast cancer cell lines, whereas the phosphorylation of AKT, EGFR, ErbB2/Her2, PDGFR, Shc, and Stat3 were elevated in only one breast cancer line compared to normal primary mammary epithelial cells and telomerase-immortalised breast epithelial cells. The same findings were confirmed by Western blotting and by kinase assays. We further substantiated the phosphorylation status of these molecules in tissue microarray slides containing 89 invasive breast cancer tissues as well as six normal mammary tissues with immunohistochemistry staining using phospho-specific antibodies. Consistent findings were obtained as greater than 70% of invasive breast carcinomas expressed moderate to high levels of phosphorylated PDK-1, AKT, p70S6K, and EGFR. In sharp contrast, phosphorylation of the same proteins was nearly undetectable or was at low levels in normal mammary tissues under the same assay. Elevated phosphorylation of PDK-1, AKT, mTOR, p70S6K, S6, EGFR, and Stat3 were highly associated with invasive breast tumours (P<0.05). Taken together, our results suggest that activation of these kinase pathways by phosphorylation may in part account for molecular pathogenesis of human breast carcinoma. Particularly, moderate to high level of PDK-1 phosphorylation was found in 86% of high-grade metastasised breast tumours. This is the first report demonstrating phosphorylation of PDK-1 is frequently elevated in breast cancer with concomitantly increased phosphorylation of downstream kinases, including AKT, mTOR, p70S6K, S6, and Stat3. This finding thus suggested PDK-1 may promote oncogenesis in part through the activation of AKT and p70S6K and rationalised that PDK-1 as well as downstream components of PDK-1 signalling pathway may be promising therapeutic targets to treat breast cancer.

3-Phosphoinositide-Dependent Protein Kinases↗

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors.

This study sought to characterize the reduced glutathione (GSH)/oxidized GSSG ratio during osteoclast differentiation and determine whether changes in the intracellular redox status regulate its differentiation through a RANKL-dependent signaling pathway. A progressive decrease of the GSH/GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the gamma-glutamylcysteinyl synthetase modifier gene. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-kappaB and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts. Furthermore, intraperitoneal injection of BSO in mice resulted in an increase in bone density and a decrease of the number of osteoclasts in bone. Conversely, glutathione repletion with either N-acetylcysteine or GSH enhanced osteoclastogenesis. These findings indicate that redox status decreases during osteoclast differentiation and that this modification directly regulates RANKL-induced osteoclastogenesis.

Active Transport, Cell Nucleus↗

Structure sensitivity of vibrational spectra of mesoporous silica SBA-15 and Pt/SBA-15.

The vibrational properties of mesoporous silica (SBA-15) were investigated by deep ultraviolet (UV) Raman and infrared spectroscopies with and without the presence of platinum nanoparticles in the mesopores that were incorporated by sonication. Raman and IR spectral line assignments were made by comparison to amorphous silicas. This procedure permitted identification of vibrations of longitudinal (LO) and transverse (TO) optical lattice modes, the presence of Si-OH, and vibrational modes associated with the presence of three-, four-, and six-membered siloxane rings. Hydraulic pressing of the mesoporous silica with pressure in the range 3-7 tons cm(-2) destroys the X-ray diffraction pattern and strongly decreases the Raman peak (D2) associated with three-membered rings at the surface. In the presence of platinum nanoparticles in the silica mesopores, a peak attributed to a Pt-O stretching vibration appears at between 530 and 580 cm(-1) in the UV-Raman spectrum, which can be used to monitor the presence of the platinum particles and their interaction with the support. The D2 feature in the UV-Raman spectra also decreases with increasing Pt loading, which is attributed to interactions of the Pt nanoparticles with the silica surface.

Journal Article↗

Possible association of the MAG locus with schizophrenia in a Chinese Han cohort of family trios.

Neurotransmitter-based hypotheses have so far led to only moderate success in predicting new pathogenetic findings in etiology of schizophrenia. On the other hand, the more recent oligodendroglia hypotheses of this disorder have been supported by an increasing body of evidence. For example, the expression level of the myelin associated glycoprotein (MAG) gene has been shown to be significantly lower in schizophrenia patient groups compared to control groups. Such an effect might be a result of genetic variations of the MAG gene. In order to test this hypothesis, we genotyped four markers within the MAG locus in 413 trios sample of the Han Chinese using allele-specific PCR. None of the four markers revealed noticeable allelic significance. However, the four-marker and two-marker haplotypes covering components rs720309 and rs720308 were observed to be significantly associated with schizophrenia (P < 0.0001) in this study. In addition, we identified one common risk haplotype TA (rs720309-rs720308, present in 78.5% of the general population) that showed increased evidence of overtransmission from parents to affected offspring (P = 0.0001). The results demonstrated MAG might play a role in genetic susceptibility to schizophrenia. Furthermore, our finding of a possible association between the MAG locus and schizophrenia is in agreement with the hypotheses of oligodendrltic and myelination dysfunction.

Adult↗

Current oscillation and low-field colossal magnetoresistance effect in phase-separated manganites.

Current-induced switching from a metallic to an insulating state is observed in phase-separated states of (La(1-y)Pr(y))0.7Ca0.3MnO3 (y=0.7) and Nd(0.5)Ca(0.5)Mn(1-z)Cr(z)O3 (z=0.03) crystals. The application of magnetic fields to this current-induced insulating state causes a pronounced low-field negative magnetoresistance effect [rho(H)/rho(0)=10(-3) at H=1 kOe]. The application of a constant voltage also causes the breakdown of the Ohmic relation above a threshold voltage. At voltages higher than this threshold value, oscillations in currents are observed. This oscillation is well reproduced by a simple model of local switching of a percolative conduction path.

Journal Article↗

High-surface-area catalyst design: Synthesis, characterization, and reaction studies of platinum nanoparticles in mesoporous SBA-15 silica.

Platinum nanoparticles in the size range of 1.7-7.1 nm were produced by alcohol reduction methods. A polymer (poly(vinylpyrrolidone), PVP) was used to stabilize the particles by capping them in aqueous solution. The particles were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). TEM investigations demonstrate that the particles have a narrow size distribution. Mesoporous SBA-15 silica with 9-nm pores was synthesized by a hydrothermal process and used as a catalyst support. After incorporation into mesoporous SBA-15 silica using low-power sonication, the catalysts were calcined to remove the stabilizing polymer from the nanoparticle surface and reduced by H2. Pt particle sizes determined from selective gas adsorption measurements are larger than those determined by bulk techniques such as XRD and TEM. Room-temperature ethylene hydrogenation was chosen as a model reaction to probe the activity of the Pt/SBA-15 materials. The reaction was shown to be structure insensitive over a series of Pt/SBA-15 materials with particle sizes between 1.7 and 3.6 nm. The hydrogenolysis of ethane on Pt particles from 1.7 to 7.1 nm was weakly structure sensitive with smaller particles demonstrating higher specific activity. Turnover rates for ethane hydrogenolysis increased monotonically with increasing metal dispersion, suggesting that coordinatively unsaturated metal atoms present in small particles are more active for C2H6 hydrogenolysis than the low index planes that dominate in large particles. An explanation for the structure sensitivity is suggested, and the potential applications of these novel supported nanocatalysts for further studies of structure-activity and structure-selectivity relationships are discussed.

Journal Article↗

Comparison of high-speed counter-current chromatography instruments for the separation of the extracts of the seeds of Oroxylum indicum.

Analytical Milli high-speed counter-current chromatography (HSCCC) was used for the selection and optimization of the two-phase solvent system to separate flavonoids from the extracts of the seeds of Oroxylum indicum. The optimum solvent system obtained from Milli-CCC was also the best solvent system for preparative HSCCC and led to the successful separation of two crude flavonoids from the seeds of O. indicum by Lab/Prep (laboratory preparative) HSCCC using different sized coils. Four flavonoids were isolated by preparative HSCCC: baicalein-7-O-diglucoside (25.0 mg, 92% purity), baicalein-7-o-glucoside (50.4 mg; 95% purity), baicalein (75 mg; purity 98%) and chrysin (100 mg; purity 98%).

Bignoniaceae↗

Molecular characterization of Sp serotype strains of infectious pancreatic necrosis virus exhibiting differences in virulence.

Infectious pancreatic necrosis virus (IPNV), a prototype virus of the family Birnaviridae, exhibits a high degree of antigenic variability, pathogenicity and virulence in salmonid species. The Genomic Segment A encodes all the structural (VP2 and VP3) and nonstructural (NS) proteins, whereas Segment B encodes the viral RNA-dependent RNA polymerase (VP1). We tested 3 different IPNV isolates (Sp103, Sp116 and Sp122) isolated during field outbreaks in Norway for their ability to cause mortality in fry and post-smolt of Atlantic salmon Salmo salar L. The cumulative mortality following experimental challenge in fry was 29% for Sp122 followed by 19% for Sp116 and 15% for Sp103. In post-smolt, the corresponding mortality rates were 79, 46 and 16%, respectively. Comparisons of the deduced amino acid sequences of Segments A and B of all 3 Sp strains revealed substitutions of residues in 13 positions, of which 6 are in VP2, 2 in VP3, and 5 in VP1. Our results suggest that these residues, especially those in the outer capsid VP2, may be involved in the virulence of IPNV. Genome Segment A of the Sp serotype is 3097 nucleotides long and contains a major open reading frame (ORF) encoding a polyprotein of 972 amino acids, which initiates at the second in-frame start codon at Position 119. This was ascertained by making mutants of Segment A clone using site-directed mutagenesis, followed by in vitro transcription-coupled translation reaction and immunoprecipitation analyses. In addition, Segment A also encodes a 15 kDa arginine-rich non-structural protein from a small ORF, preceding and partially overlapping the polyprotein ORF, which is truncated to 12 kDa in the virulent Sp122 strain. Moreover, Segment A could encode a novel, putative 25 kDa protein from another ORF between VP2 and VP4 coding regions, which is only detected in the Sp serotype. Segment B is 2777 nucleotides long and encodes in a single large ORF (a polypeptide of 844 amino acid residues), VP1.

Amino Acid Sequence↗

Role of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) on cellular defence against oxidative injury by gamma-rays.

PURPOSE: To investigate the regulation of NADPH-producing isocitrate dehydrogenase (ICDH) in cytosol (IDPc) and mitochondria (IDPm) upon gamma-ray irradiation, and the roles of IDPc and IDPm in the protection against cellular damage induced by gamma-ray irradiation. MATERIALS AND METHODS: Changes of IDPc and IDPm proteins upon gamma-ray irradiation to NIH3T3 cells were analysed by immunoblotting. To increase or decrease the expression of IDPc or IDPm, NIH3T3 cells were stably transfected with mouse IDPc or IDPm cDNA in either the sense or the antisense direction. The transfected cells with either increased or decreased IDPc or IDPm were exposed to gamma-rays, and the levels of reactive oxygen species generation, protein oxidation and lipid peroxidation were measured. RESULTS: Both IDPc and IDPm activities were induced by gamma-ray in NIH3T3 cells. Cells with decreased expression of IDPc or IDPm had elevated reactive oxygen species generation, lipid peroxidation and protein oxidation. Conversely, overproduction of IDPc or IDPm protein partially protected the cells from oxidative damage induced by gamma-ray irradiation. CONCLUSIONS: The protective role of IDPc and IDPm against gamma-ray-induced cellular damage can be attributed to elevated NADPH, reducing equivalents needed for recycling reduced glutathione in the cytosol and mitochondria. Thus, a primary biological function of the ICDHs may be production of NADPH, which is a prerequisite for some cellular defence systems against oxidative damage.

Animals↗

Identification, detection, and spatial resolution of Clostridium populations responsible for cellulose degradation in a methanogenic landfill leachate bioreactor.

An anaerobic landfill leachate bioreactor was operated with crystalline cellulose and sterile landfill leachate until a steady state was reached. Cellulose hydrolysis, acidogenesis, and methanogenesis were measured. Microorganisms attached to the cellulose surfaces were hypothesized to be the cellulose hydrolyzers. 16S rRNA gene clone libraries were prepared from this attached fraction and also from the mixed fraction (biomass associated with cellulose particles and in the planktonic phase). Both clone libraries were dominated by Firmicutes phylum sequences (100% of the attached library and 90% of the mixed library), and the majority fell into one of five lineages of the clostridia. Clone group 1 (most closely related to Clostridium stercorarium), clone group 2 (most closely related to Clostridium thermocellum), and clone group 5 (most closely related to Bacteroides cellulosolvens) comprised sequences in Clostridium group III. Clone group 3 sequences were in Clostridium group XIVa (most closely related to Clostridium sp. strain XB90). Clone group 4 sequences were affiliated with a deeply branching clostridial lineage peripherally associated with Clostridium group VI. This monophyletic group comprises a new Clostridium cluster, designated cluster VIa. Specific fluorescence in situ hybridization (FISH) probes for the five groups were designed and synthesized, and it was demonstrated in FISH experiments that bacteria targeted by the probes for clone groups 1, 2, 4, and 5 were very abundant on the surfaces of the cellulose particles and likely the key cellulolytic microorganisms in the landfill bioreactor. The FISH probe for clone group 3 targeted cells in the planktonic phase, and these organisms were hypothesized to be glucose fermenters.

Base Sequence↗

ATTEMPTS: a heparin/protamine-based delivery system for enzyme drugs.

A prodrug delivery system termed "Antibody Targeted, Triggered, Electrically Modified Prodrug-Type Strategy (ATTEMPTS)" has been developed to permit the antibody-directed administration of inactive enzyme drug including tissue-type plasminogen activator (tPA), and allow a subsequent triggered release of the active tPA at the target site. Cation-modified tPA (mtPA) was attached to a heparin-antifibrin complex via ionic interaction, and the active tPA can subsequently be released by the addition of protamine, a competitive heparin inhibitor. Anti-fibrin IgG was conjugated to heparin via an end-point attachment to form the heparin-antifibrin complex which provides the targeting efficiency of the final heparin/mtPA complex. Cation modification was performed by either chemical conjugation by linking (Arg)7Cys to tPA with N-succinimidy-3-(2-pyridyldithio) propionate or by recombinant DNA methods. Results show that the modification process did not significantly alter the specific activity of tPA with regard to plasminogen activation, fibrin-binding ability, and response toward fibrinogen. The complexes of both modified tPA-heparin did not yield any intrinsic catalytic activity owing to the blockage of the active site of tPA by the attached heparin. On the other hand, heparin-induced inhibition of modified tPA activity was reversed by adding protamine, which is similar to that of a prodrug delivery system. These results suggest that heparin/protamine-based enzyme delivery systems may be a useful tool to improve current enzyme therapeutic status, as well as thrombolytic therapy, by both regulating the release of active enzyme and aborting the associated systemic toxic effect. Currently, modification of enzyme drugs has been optimized by recombinant DNA technology assisted by computer simulation. In addition, the original strategy has been revised to obtain enhanced therapeutic efficacy.

Base Sequence↗

Hyaluronan metabolism in rat tail skin following blockage of the lymphatic circulation.

This study was undertaken to explore the effects of lymphatic blockage on the metabolism of hyaluronan in the skin. In initial experiments, [3H] hyaluronan was injected subcutaneously into the tail skin of rats that either had no surgical intervention (control) or into those that had their lymphatic drainage blocked two hours earlier (acute lymphedema) or after the lymphatics had been blocked for three months (chronic lymphedema). The removal of tritiated hyaluronan from the injection sites was determined by the appearance of [3H] in the plasma. The results showed that the clearance of injected hyaluronan was delayed in rats with lymphatic blockage. The half- life of injected hyaluronan in the controls was approximately 70-75 hr, compared with approximately 105-110 hr in the lymph blocking rats. The levels of radioactivity in the plasma from rats with both acute and chronically blocked lymphatics were lower than that of control rats during the entire follow up period. In addition, biochemical analysis revealed that there was a significant increased amount of hyaluronan in the tail skin three months after lymphatic blocking. These results suggest that lymph absorption is an important factor in the transport of hyaluronan from the interstitium. Blockage of regional draining lymphatics likely impairs the catabolism of hyaluronan, which stagnates in skin tissue.

Animals↗

Identification of genetic alterations in the TGFbeta type II receptor gene promoter.

Modifications in the control sequences of tumor suppressor genes have been found to play a role in the activation or inactivation of these genes and may play an important role in tumorigenesis. For example, hypermethylation of CpG islands and promoter polymorphisms have been found to be involved in transcriptional repression. A decrease in the levels of expression of one such tumor suppressor gene, the TGFbeta type II receptor (TbetaR-II), has been associated with increased tumorigenicity in a number of human tumors. Genetic alterations have been described in several tumor types in the coding region of this gene. However, no comprehensive search for genetic alterations in the TbetaR-II promoter has been reported. Genetic alterations in the promoter of the TbetaR-II gene could inhibit binding of putative regulatory factors. For example, we have reported a A-364-G alteration in the TbetaR-II promoter, which results in decreased transcriptional activity. In this study, we analyzed the 1.0kb region upstream of the TbetaR-II transcriptional start site and found genetic alterations in 46% of the head and neck squamous cell carcinoma (SqCC) samples examined. The most frequent alteration was a G-875-A alteration, present in 41.6% of the samples. Analysis of normal healthy individuals showed a similar frequency of this alteration, suggesting that alterations within the TbetaR-II promoter are unlikely to account for the decreased expression of TbetaR-II in head and neck SqCC.

Base Sequence↗

Identification and sequencing of the Syrian Golden hamster (Mesocricetus auratus) p16(INK4a) and p15(INK4b) cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells.

Previous studies have shown that the p16(INK4a) tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15(INK4b) gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden hamster (Mesocricetus auratus) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16(INK4a) and p15(INK4b) genes in two experimental hamster models for human pancreatic and oral carcinogenesis. First, hamster p16(INK4a) and p15(INK4b) cDNAs were cloned and sequenced. The hamster p16(INK4a) cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16(INK4a) sequences, respectively. Similarly, the hamster p15(INK4b) cDNA ORF shares 82% and 89% sequence identity with human and mouse p15(INK4b), respectively. Second, a deletion analysis of hamster p16(INK4a) and p15(INK4b) genes was performed for several tumorigenic and non-tumorigenic hamster cell lines and revealed that both p16(INK4a) and p15(INK4b) were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16(INK4a) and p15(INK4b) genes plays a prominent role in hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.

Amino Acid Sequence↗