Biomedical subjects

A Huber

Publications and source records attributed to A Huber.

At least 55 records · Page 3Linked to original sources

PubMed2001

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Morphological evidence.

The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic transmitter mechanism in the enteric nervous system. Our aim was to localize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was found in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in cells perivascularly scattered throughout the circular muscle layer. cGK-I immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less intensively in the outer circular layer. Weak cGK-I staining occurred in nerve cells within the myenteric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a sequence of neuronal NO release, activation of ICC, and consecutive smooth muscle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.

Animals↗

PubMed2001

A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency.

Plectin is a cytoskeleton linker protein expressed in a variety of tissues including skin, muscle, and nerves. Mutations in its gene are associated with epidermolysis bullosa simplex with late-onset muscular dystrophy. Whereas in most of these patients the pathogenic events are mediated by nonsense-mediated mRNA decay, the consequences of an in-frame mutation are less clear. We analyzed a patient with compound heterozygosity for a 3-bp insertion at position 1287 leading to the insertion of leucine as well as the missense mutation Q1518X leading to a stop codon. The presence of plectin mRNA was demonstrated by a RNase protection assay. However, a marked reduction of plectin protein was found using immunofluorescence microscopy of the patient's skin and Western blot analysis of the patient's cultured keratinocytes. The loss of plectin protein was associated with morphological alterations in plectin-containing structures of the dermo-epidermal junction, in skeletal muscle, and in nerves as detected by electron microscopy. In an in vitro overlay assay using recombinant plectin peptides spanning exons 2 to 15 the insertion of leucine resulted in markedly increased self-aggregation of plectin peptides. These results describe for the first time the functional consequences of an in-frame insertion mutation in humans.

Base Sequence↗

PubMed2001

Brownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling.

Brownian dynamics (BD) simulations test for channeling of the substrate, glyceraldehyde 3-phosphate (GAP), as it passes between the enzymes fructose-1,6-bisphosphate aldolase (aldolase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). First, BD simulations determined the favorable complexes between aldolase and GAPDH; two adjacent subunits of GAPDH form salt bridges with two subunits of aldolase. These intermolecular contacts provide a strong electrostatic interaction between the enzymes. Second, BD simulates GAP moving out of the active site of the A or D aldolase subunit and entering any of the four active sites of GAPDH. The efficiency of transfer is determined as the relative number of BD trajectories that reached any active site of GAPDH. The distribution functions of the transfer time were calculated based on the duration of successful trajectories. BD simulations of the GAP binding from solution to aldolase/GAPDH complex were compared to the channeling simulations. The efficiency of transfer of GAP within an aldolase/GAPDH complex was 2 to 3% compared to 1.3% when GAP was binding to GAPDH from solution. There is a preference for GAP channeling between aldolase and GAPDH when compared to binding from solution. However, this preference is not large enough to be considered as a theoretical proof of channeling between these proteins.

Binding Sites↗

PubMed2001

Scaffolding proteins organize multimolecular protein complexes for sensory signal transduction.

Scaffolding proteins composed of protein-protein interaction domains have emerged as organizers of multiprotein complexes in diverse cellular compartments, including neuronal synapses, cell-cell junctions of epithelial cells, and the stimulus perceiving structures of sensory neurons. This review focuses on the INAD-assembled signalling complex of Drosophila photoreceptors, which organizes key components of the phototransduction cascade into a multiprotein signal transduction unit. The structure, the physiological consequences, and the assembly and targeting of the members of the INAD signalling complex will be described. In addition, the existence of signalling complexes in vertebrate photoreceptors, olfactory neurons and mechanosensitive hair cells will be discussed.

Animals↗

PubMed2001

Diffusion-weighted magnetic resonance imaging of spinal bone marrow.

Diffusion-weighted (DW) imaging is an alternative source of image contrast. DW imaging enables to measure the random motion of free water protons on a molecular basis by using different imaging sequences including steady-state free precession imaging, navigated spin-echo DW imaging, and single-shot echo planar imaging. Analysis of intravoxel incoherent motion of water protons is a promising tool that has shown to be of value in the differential diagnosis between benign and malignant spontaneous vertebral fractures. Acute benign osteoporotic fractures show hypo- or isointense signal on DW sequences that reflects persistent free water proton mobility. With increasing diffusion strength a substantial signal loss is found. Metastatic fractures show hyperintensity compared with normal surrounding bone marrow probably due to altered water proton mobility within neoplasm. The ability of the different methods for DW imaging to differentiate other bone marrow alterations needs to be investigated in further studies.

Bone Marrow↗

PubMed2001

Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal.

BACKGROUND: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD). METHODS: Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined. RESULTS: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments. CONCLUSIONS: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.

Adult↗

PubMed2001

Selection of catalytically active biotin ligase and trypsin mutants by phage display.

Phage display has been shown to facilitate greatly the selection of polypeptides with desired properties by establishing a direct link between the polypeptide and the gene that encodes it. However, selection for catalytic activities displayed on phage remains a challenge, since reaction products diffuse away from the enzyme and make it difficult to recover catalytically active phage-enzymes. We have recently described a selection methodology in which the reaction substrate (and eventually the reaction product) is anchored on calmodulin-tagged phage-enzymes by means of a calmodulin binding peptide. Phage displaying a catalytic activity are physically isolated by means of affinity reagents specific for the product of reaction. In this study, we investigated the efficiency of selection for catalysis by phage display, using a ligase (the Escherichia coli biotin ligase BirA) and an endopeptidase (the rat trypsin His57--> Ala mutant) as model enzymes. These enzymes could be displayed on phage as fusion proteins with calmodulin and the minor coat protein pIII. Both the display of functional enzyme and the efficiency of selection for catalysis were significantly improved by using phage vectors, rather than phagemid vectors. In model selection experiments, phage displaying BirA were consistently enriched (between 4-fold and 800-fold) per round of panning, relative to negative controls. Phage displaying the trypsin His57-->Ala mutant, a relatively inefficient endopeptidase which cleaves a specific dipeptide sequence, were enriched (between 15-fold and 2000-fold), relative to negative controls. In order to improve the catalytic properties of the trypsin His57-->Ala mutant, we constructed a combinatorial phage display library of trypsin mutants. Selection of catalytically active phage-enzymes was evidentiated by increasing phage titres at the different rounds of panning relative to negative control selections, but mutants with catalytic properties superior to those of trypsin His57-->Ala mutant could not be isolated. The results obtained provide evidence that catalytic activities can be recovered using phage display technology, but stress the importance of both library design and stringent biopanning conditions for the recovery of novel enzymes.

Amino Acid Sequence↗

PubMed2001

Is the Er:YAG laser damaging to inner ear function?

OBJECTIVE: To assess whether the use of the Er:YAG laser in middle ear surgery has negative effects on inner ear function. STUDY DESIGN: Prospective. PATIENTS: Forty-nine patients with a 4- to 18-month postoperative audiologic follow-up were included in the study (24 stapedotomies, 23 malleostapedotomies, 1 surgery for congenital ear atresia, and 1 tympanoplasty). Twenty patients with conventional stapedotomy formed a control group. RESULTS: No statistically significant differences in preoperative and postoperative bone conduction thresholds and no impairment of postoperative air conduction thresholds were found. There was no significant difference between the results of the laser and the conventional stapedotomy. In addition, no relevant correlation between applied laser energy and postoperative hearing results were found. In summary, the authors were unable to find a negative effect of the Er:YAG laser on inner ear function at the 4- to 18-month audiometric follow-up. CONCLUSION: The clinical use of the Er:YAG laser with the system used in this study poses no risk to inner ear function if the total amount of energy is kept within the limits applied in this study.

Adolescent↗

PubMed2001

ECG-gated reconstructed multi-detector row CT coronary angiography: effect of varying trigger delay on image quality.

PURPOSE: To evaluate the effectiveness of electrocardiographically (ECG)-gated retrospective image reconstruction for multi-detector row computed tomographic (CT) coronary angiography in reducing cardiac motion artifacts and to evaluate the influence of heart rate on cardiac image quality. MATERIALS AND METHODS: Sixty-five patients with different heart rates underwent coronary CT angiography. Raw helical CT data and ECG tracings were combined to retrospectively reconstruct at the defined consecutive z position with a temporal resolution of 250 msec per section. The starting points of the reconstruction were chosen between 30% and 80% of the R-R intervals. The relationships between heart rate, trigger delay, and image quality were analyzed. RESULTS: Optimal image quality was achieved with a 50% trigger delay for the right coronary artery and 60% for the left circumflex coronary artery. Optimal image quality for the left anterior descending coronary artery was equally obtained at 50% and 60% triggering. A significant negative correlation was observed between heart rate and image quality (P <.05). The best image quality was achieved when the heart rate was less than 74.5 beats per minute. CONCLUSION: To achieve high image quality, the heart rate should be sufficiently slow. Selection of appropriate trigger delays and a decreasing heart rate are effective to reduce cardiac motion artifacts.

Adult↗

PubMed2001

Intraoperative assessment of stapes movement.

A method is described that allows, for the first time, intraoperative vibration modes assessment of the acoustically stimulated stapes by means of scanning laser Doppler interferometry (LDI). The study was designed to answer the following questions: 1) Is LDI practical for taking measurements during surgery? 2) Are the results comparable to the findings in temporal bone preparations? and 3) Do the vibration characteristics of the stapes change after the posterior incudal ligament is detached from the incus? Seven patients with profound bilateral hearing loss who were undergoing cochlear implantation were included in the study. The measurement system was easily applicable for intraoperative measurements and allowed contact-free analysis with very high accuracy. No major differences in the results from the live human subjects and temporal bone preparations were observed. The stapes movement was predominantly pistonlike at the lower frequencies and became complex at higher frequencies. Sacrificing the posterior incudal ligament had no statistically significant effect on stapes vibration.

Acoustic Stimulation↗

PubMed2001

Diagnostic value of increased diffusion weighting of a steady-state free precession sequence for differentiating acute benign osteoporotic fractures from pathologic vertebral compression fractures.

BACKGROUND AND PURPOSE: Differentiating acute benign from neoplastic vertebral compression fractures can pose a problem in differential diagnosis on routine MR sequences, as signal changes can be quite similar. Our purpose was to assess the value of increasing the diffusion weighting of a diffusion-weighted steady-state free precession (SSFP) sequence for differentiating these two types of vertebral compression fractures. METHODS: Twenty-nine patients with 32 acute vertebral compression fractures caused by osteoporosis (n = 15) or malignancy (n = 17) were examined with a diffusion-weighted SSFP sequence, a T1-weighted spin-echo sequence, and a short-inversion-time inversion recovery sequence. The SSFP sequence was performed with increased diffusion weighting (delta = 0.6, 3.0, 6.0, and 9.0 ms). The signal intensities of the fractured vertebral bodies were rated on a five-point scale from markedly hypointense to markedly hyperintense relative to normal adjacent vertebral bodies. Quantitative analysis was performed by region-of-interest measurements and by calculating the bone marrow contrast ratio. Statistical analysis was performed with the Mann Whitney U test and Student's t test. RESULTS: At delta = 3 ms, the osteoporotic fractures yielded hypointense signal in seven cases, isointense signal in six, and hyperintense signal in two. The fractures showed a progressive signal loss with increased diffusion weighting, so that hypointensity was reached in all but one case. All metastatic fractures had hyperintense signal with delta = 3 and 6.0 ms. With delta = 9.0 ms, four fractures became isointense. CONCLUSION: Increasing diffusion weighting can reduce false-positive hyperintense osteoporotic fractures or make hypointensity more obvious in cases of osteoporotic fractures.

Acute Disease↗

PubMed2001

High-resolution MR angiography: results in diseased arteries.

The purpose of this study was to investigate the value of a respiratory-gated three-dimensional (3D) magnetic resonance angiographic technique (MRCA) in identifying coronary arteries in healthy volunteers and patients with proximal coronary artery stenoses and to compare the results of the navigator echo technique in the assessment of coronary artery stenosis with conventional coronary angiography. Twenty healthy volunteers and twenty patients with proximal coronary artery stenosis were examined at 1.5 Teslas with a cardiac-gated and retrospective respiratory-gated 3D gradient echo sequence. Visualization of the main coronary arteries was analyzed after curved MPR-reconstruction in three defined segments. For the assessment of image quality, a grading system including six scores was used to evaluate 400 vessel segments. Detection of coronary artery stenosis was compared with conventional coronary angiography by two blinded readers. In healthy volunteers, an image quality with a score of at least 3 (i.e., completely identified coronary arteries with major luminal irregularities) was found in 55% for the proximal segment, 47% for the middle segment and 20% for the distal coronary artery segment. Respective data for patients were 69% for the proximal segment, 47% for the middle segment and 20% for the distal segment. In contrast to other studies, we compared MRCA and conventional coronary angiography in the assessment of stenoses for all coronary vessels and for selected coronary vessels with high image quality. For the assessment of coronary artery stenoses (n = 53), sensitivity was 73% and specificity was 50% after evaluation of all patients by two blinded readers. A sensitivity of 79% and a specificity of 54% were found for evaluation of coronary vessels with an image quality score of at least 3. With the navigator echo MR technique, a complete 3D visualization of the main coronary arteries is possible in cases with variable image quality, but further experience and improvement of the prospective navigator echo sequence using shorter acquisition times is necessary for reliable assessment of coronary artery stenoses.

Coronary Angiography↗

PubMed2001

Input pathways and river load of pesticides in Germany--a national scale modeling assessment.

A model has been developed which estimates the magnitude and the spatial distribution of pesticide losses from diffuse sources (surface run-off, tile drains and spraydrift) into surface waters for the entire area of Germany. The cumulative annual losses of 42 active ingredients applied to 11 field crops, orchards and vineyards are calculated for river basins in Germany based on grid maps with a resolution of 1 x 1 km2. The model validation showed a sufficient degree of accuracy of the model results compared to measured pesticide loads in 13 small catchments. According to the model results the pesticide input from diffuse sources into surface waters amounted to 13.8 t in 1994 aggregated for the entire area of Germany. Input via surface runoff contributed 9.1 t while tile drainage was 1.4 t and spraydrift 3.4 t respectively. Alongside the model calculations empirical data of the pesticide load of rivers in Germany are presented. A comparison of the measured river loads with the modeled inputs from non-point sources leads to the conclusion that in most regions of Germany the largest portion of the load is due to the input from farm effluents.

Agriculture↗

PubMed2001

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience.

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.

Aged↗

PubMed2001

Modeling pesticide losses from diffuse sources in Germany.

A GIS-based model estimates the losses from diffuse sources in surface waters in Germany for 42 active ingredients applied to 11 field crops, vineyards and orchards. For the following pathways of entry: tile drainage, runoff and spray drift, the calculated mean pesticide input amounts to 1490 kg/year, 9060 kg/year and 3350 kg/year, respectively, in 1994. The model results are highly sensitive to the model parameters, primarily the chemical properties of the active ingredients. The modeled water inputs were compared with measured pesticide loads in smaller catchments and large river basins to validate model results. Both datasets agree as to the order of magnitude, nevertheless due to the scale of the study the results should be addressed mainly to comparative interpretations with the focus on the proportions between different active ingredients, soil regions, climates and application periods.

Agriculture↗

PubMed2000

Sensitivity of trypanosomatid protozoa to DFMO and metabolic turnover of ornithine decarboxylase.

alpha-Difluoromethylornithine (DFMO), the specific and irreversible inhibitor of ornithine decarboxylase (ODC), was able to induce the arrest of proliferation in Leishmania mexicana and ODC-transformed Trypanosoma cruzi cultures grown in a semi-defined medium essentially free of polyamines. Conversely, Crithidia fasciculata and Phytomonas 274 were not affected by the inhibitor. The drug-resistance of Crithidia and Phytomonas was neither caused by an impairment of DFMO uptake nor by a decrease of the enzyme affinity for the inhibitor. We were also able to rule out the possibility of ODC overexpression in the drug-tolerant parasites. The measurements of ODC metabolic turnover indicated that the enzymes from Crithidia and Phytomonas have a short half-life of 20-40 min, while ODC from Leishmania and transgenic Trypanosoma cruzi are rather stable with a half-life longer than 6 hours. Analyses of polyamine internal pools under different growth conditions have shown that DFMO was able to markedly decrease the levels of putrescine and spermidine in all parasites, but the depletion of spermidine was higher in trypanosomatids containing an ODC with slow turnover. Our results suggest that in these parasites cultivated in the presence of the drug, spermidine might decrease below critical levels needed to maintain trypanothione concentrations or other conditions essential for normal proliferation.

Animals↗

PubMed2000

Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta.

Calcium release from the endoplasmic reticulum controls a number of cellular processes, including proliferation and contraction of smooth muscle and other cells. Calcium release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores is negatively regulated by binding of calmodulin to the IP3 receptor (IP3R) and the NO/cGMP/cGMP kinase I (cGKI) signalling pathway. Activation of cGKI decreases IP3-stimulated elevations in intracellular calcium, induces smooth muscle relaxation and contributes to the antiproliferative and pro-apoptotic effects of NO/cGMP. Here we show that, in microsomal smooth muscle membranes, cGKIbeta phosphorylated the IP3R and cGKIbeta, and a protein of relative molecular mass 125,000 which we now identify as the IP3R-associated cGMP kinase substrate (IRAG). These proteins were co-immunoprecipitated by antibodies directed against cGKI, IP3R or IRAG. IRAG was found in many tissues including aorta, trachea and uterus, and was localized perinuclearly after heterologous expression in COS-7 cells. Bradykinin-stimulated calcium release was not affected by the expression of either IRAG or cGKIbeta, which we tested in the absence and presence of cGMP. However, calcium release was inhibited after co-expression of IRAG and cGKIbeta in the presence of cGMP. These results identify IRAG as an essential NO/cGKI-dependent regulator of IP3-induced calcium release.

Amino Acid Sequence↗

PubMed2000

Cysteine-rich protein 2, a novel substrate for cGMP kinase I in enteric neurons and intestinal smooth muscle.

Nitric oxide/cGMP/cGMP kinase I (cGKI) signaling causes relaxation of intestinal smooth muscle. In the gastrointestinal tract substrates of cGKI have not been identified yet. In the present study a protein interacting with cGKIbeta has been isolated from a rat intestinal cDNA library using the yeast two-hybrid system. The protein was identified as cysteine-rich protein 2 (CRP2), recently cloned from rat brain (Okano, I., Yamamoto, T., Kaji, A., Kimura, T., Mizuno, K., and Nakamura, T. (1993) FEBS Lett. 333, 51-55). Recombinant CRP2 is specifically phosphorylated by cGKs but not by cAMP kinase in vitro. Co-transfection of CRP2 and cGKIbeta into COS cells confirmed the phosphorylation of CRP2 in vivo. Cyclic GMP kinase I phosphorylated CRP2 at Ser-104, because the mutation to Ala completely prevented the in vivo phosphorylation. Immunohistochemical analysis using confocal laser scan microscopy showed a co-localization of CRP2 and cGKI in the inner part of the circular muscle layer, in the muscularis mucosae, and in specific neurons of the myenteric and submucosal plexus. The co-localization together with the specific phosphorylation of CRP2 by cGKI in vitro and in vivo suggests that CRP2 is a novel substrate of cGKI in neurons and smooth muscle of the small intestine.

Amino Acid Sequence↗