Biomedical subjects

G Jayaraman

Publications and source records attributed to G Jayaraman.

At least 19 recordsLinked to original sources

PubMed2006

Exploring the environmental preference of weak interactions in (alpha/beta)8 barrel proteins.

The environmental preference for the occurrence of noncanonical hydrogen bonding and cation-pi interactions, in a data set containing 71 nonredundant (alpha/beta)(8) barrel proteins, with respect to amino acid type, secondary structure, solvent accessibility, and stabilizing residues has been performed. Our analysis reveals some important findings, which include (a) higher contribution of weak interactions mediated by main-chain atoms irrespective of the amino acids involved; (b) domination of the aromatic amino acids among interactions involving side-chain atoms; (c) involvement of strands as the principal secondary structural unit, accommodating cross strand ion pair interaction and clustering of aromatic amino acid residues; (d) significant contribution to weak interactions occur in the solvent exposed areas of the protein; (e) majority of the interactions involve long-range contacts; (f) the preference of Arg is higher than Lys to form cation-pi interaction; and (g) probability of theoretically predicted stabilizing amino acid residues involved in weak interaction is higher for polar amino acids such as Trp, Glu, and Gln. On the whole, the present study reveals that the weak interactions contribute to the global stability of (alpha/beta)(8) TIM-barrel proteins in an environment-specific manner, which can possibly be exploited for protein engineering applications.

Amino Acids↗

PubMed2006

Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: Modulation by bacoside A.

Cigarette smoking is associated with the development of several diseases and antioxidants play a major role in the prevention of smoking-related diseases. Apoptosis is suggested as a possible contributing factor in the pathogenesis of smoking-induced toxicity. Therefore the present study was designed to investigate the influence of chronic cigarette smoke exposure on apoptosis and the modulatory effect of bacoside A (triterpenoid saponin isolated from the plant Bacopa monniera) on smoking-induced apoptosis in rat brain. Adult male albino rats of Wistar strain were exposed to cigarette smoke and simultaneously administered with bacoside A (10 mg/kg b.w./day, orally) for a period of 12 weeks. Expression of brain hsp70 was analyzed by Western blotting. Apoptosis was identified by DNA fragmentation, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick end labeling (TUNEL) staining and transmission electron microscopy. The results showed that exposure to cigarette smoke induced hsp70 expression and apoptosis as characterized by DNA laddering, increased TUNEL-positive cells and ultrastructural apoptotic features in the brain. Administration of bacoside A prevented expression of hsp70 and neuronal apoptosis during cigarette smoking. We speculate that apoptosis may be responsible for the smoking-induced brain damage and bacoside A can protect the brain from the toxic effects of cigarette smoking.

Animals↗

PubMed2005

Conformation and stability of elastase from Atlantic cod, Gadus morhua.

Metal binding and conformational stability characteristics of psychrophilic elastase (ACE) from Atlantic cod (Gadus morhua) has been investigated. Chelation to Ca(2+) was found to be important for maintaining the biologically active conformation and for the thermal stability of the enzyme. However, presence of metal ions such as Zn(2+), Fe(3+) and Cu(2+) was found to inhibit its hydrolytic activity and so did the chelating agent EDTA. Both pH and guanidinium chloride induced denaturation of the enzyme was followed by monitoring the changes in the tryptophan fluorescence. ACE exhibited a simple two-state unfolding pattern in both acidic and basic conditions with the midpoint of transition at pH values 4.08 and 10.29, respectively. Guanidinium chloride and heat induced denaturation of the enzyme was investigated at two pH values, 5.50 and 8.00, wherein the enzyme possesses similar tertiary structure but differ in its hydrolytic activity. Guanidinium chloride induced denaturation indicated that the enzyme unfolds with a C(m) of 1.53 M at pH 8.0 and a DeltaG(H2O) of 6.91 kJ mol(-1) (28.65 J mol(-1) residue(-1)) which is the lowest reported for psychrophilic enzymes investigated till-date. However, at pH 5.50, DeltaG(H2O) value is slightly lowered by 0.65 kJ mol(-1) consistent with the observed increase in the apparent quenching constant obtained with acrylamide. On the other hand, increase in T(m) by 38.45 degrees C was observed for the enzyme at acid pH (5.50) in comparison to the heat induced unfolding at pH 8.0. The increase in the apparent T(m) has been attributed to the possible weak intermolecular association of the enzyme molecules at moderately high temperatures that is favoured by the increase in the accessible surface area / dynamics under acidic conditions. The stability characteristics of ACE have been compared with the available data for mesophilic porcine pancreatic elastase and possible mechanism for the low temperature adaptation of ACE has been proposed.

Adaptation, Physiological↗

PubMed2005

Effect of L-carnitine on nucleic acid status of aged rat brain.

The accumulation of damage to DNA plays a significant role in the etiology of the aging process. The importance of nutrition in delaying the aging process is well recognized. L-carnitine is a quaternary ammonium compound heterogeneously distributed in the brain. In the present study the effect of L-carnitine on DNA damage of various brain regions was investigated in a duration dependent way. Male albino rats aged 4 and 24 months were administered L-carnitine (300 mg/kg body weight/day) for 7,14 and 21 days. The activities of antioxidant enzymes, the levels of nucleic acids and the extent of DNA damage were measured in cortex, hippocampus, striatum, hypothalamus and cerebellum. Our results clearly showed that the activities of super oxide dismutase, glutathione peroxidase and the levels of DNA and RNA were significantly low in cortex, hippocampus and striatum of aged rat brain when compared with that of young rats. The regions that have lower antioxidants status are highly susceptible to oxidative DNA damage. Treatment with L-carnitine in aged rats enhanced the nucleic acid, antioxidant activity in a duration dependent manner with maximal effect after 21 days whereas no significant changes could be observed in the brain of young rats. These results suggest that that L-carnitine administration prevents age-related increment of DNA damage, thereby confirming the neuroprotective action of L-carnitine against aging.

Aging↗

PubMed2004

Enhanced catalytic and conformational stability of Atlantic cod trypsin upon neoglycosylation.

The applicability of psychrophilic enzymes is limited because of their lower thermodynamic stability in spite of their higher catalytic rate. In this study, we have shown that the thermodynamic stability of the psychrophilic Atlantic cod trypsin could be enhanced appreciably by covalent chemical modification with oxidized sucrose polymer without affecting its hydrolytic activity. The acquired stability of cod trypsin was found to be on par with the mesophilic porcine trypsin.

Animals↗

PubMed2004

Effect of boundary absorption in dispersion in Casson fluid flow in a tube.

The combined effect of yield stress and irreversible boundary reaction on dispersion process in a Casson fluid flowing in a conduit (pipe/channel) is studied using the generalized dispersion model proposed by Sankarasubramanian and Gill (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A 333:115-132, 1973). The study describes the development of dispersive transport following the injection of a tracer in terms of the three effective transport coefficients, viz., exchange, convection, and dispersion coefficients. The exchange coefficient does not depend on yield stress but the convection and dispersion coefficients depend on yield stress or equivalently plug flow region. For large times, when the plug flow radius is one-tenth of pipe radius, the convective coefficient is reduced by 0.41 times of the corresponding value for a Newtonian fluid at equivalent wall absorption parameter; in channel case the reduction is by 39%. It is seen that the asymptotic dispersion coefficient decreases with increase in wall absorption parameter and yield stress of the fluid. When the plug radius in pipe (channel) is 0.1, depending upon the values of wall absorption parameter, say (0.01-100) the reduction factor in dispersion coefficient is in the range (0.1-0.3) in comparison to the values of the Newtonian case. The results reduce to those of Sankarasubramanian and Gill (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A 333:115-132, 1973) when there is no yield stress for the pipe flow analysis and to those of Dash et al. (Dash, R. K., G. Jayaraman, and K. N. Mehta. Ann. Biomed. Eng. 28:373-385, 2000) when there is no interphase mass transfer. The study can be used as a starting first approximation solution for studying the dispersion in the cardiovascular system.

Absorption↗

PubMed2000

Binding of a de novo designed peptide to specific glycosaminoglycans.

The binding of glycosaminoglycans to a synthetic peptide (SKAQKAQAKQAKQAQKAQKAQAKQAKQW-CONH(2)), consisting of a hybrid consensus heparin binding sequence, is studied using circular dichroism, fluorescence anisotropy and nuclear magnetic resonance techniques. The results unveil certain novel features, most importantly, the peptide binds preferentially to iduronic acid containing glycosaminoglycans and the dissociation constant for the peptide-heparin complex was found to be 30 nM. Interestingly, higher order intermolecular association(s)/aggregation was not observed, especially at saturating concentrations of the ligand. The helical structure of the peptide backbone, induced upon binding to a particular glycosaminoglycan is directly related to their binding affinity. In our opinion, studies on such unconventional hybrid peptide sequences containing low density basic amino acid residues would lead to the design of sequence specific glycosaminoglycan binding peptides.

Amino Acid Sequence↗

PubMed2000

Chemical hypoxia-induced increases in dopamine D1A receptor mRNA in renal epithelial cells are mediated by nitric oxide.

Nitric oxide (NO) and dopamine (DA) have similar effects on renal function, with both having natriuretic and diuretic effects mediated by vascular and tubular mechanisms. Renal ischaemia or hypoxia have been shown to influence the activity of both systems. However, it is not known whether there is any crosstalk between the NO and dopaminergic systems in the kidney. Here using the porcine proximal tubule-like renal epithelial LLC-PK1 cell line as a model system, we determined whether exposure of cells to chemical hypoxia altered the steady-state levels of D1A receptor mRNA and whether the changes involved the NO system. Exposure of LLC-PK1 cells to chemical hypoxia resulted in a marked increase in D1A receptor mRNA levels as measured by reverse transcription-polymerase chain reaction (RT-PCR). The increased levels of D1A receptor mRNA following hypoxia were blocked by the NO synthase inhibitors NG-nitro-L-arginine methylester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA). Further evidence that the NO system exerted positive effects on D1A receptor gene expression came from finding that the NO donor sodium nitroprusside, the NO precursor L-arginine and the guanosine 3', 5'-cyclic monophosphate (cyclic GMP) analogue 8-Br-cGMP all increased D1A receptor mRNA levels in LLC-PK1 cells. These results indicate that expression of the D1A receptor in LLC-PK1 cells can be positively regulated by the NO system. Such an interaction between the renal NO and DA systems may contribute to the reported protective effects that NO and DA exert upon the kidney under conditions of ischaemia.

Animals↗

PubMed2000

Torsional strength of the radius after osteofasciocutaneous free flap harvest with and without primary bone plating.

The osteocutaneous radial forearm free flap (OCRFFF) has not gained widespread popularity in mandibular reconstruction, primarily because of concerns about pathologic fracture of the weakened radius. This study examines the effectiveness of plate fixation of the radius bone after harvest of the OCRFFF as a mechanism to minimize donor-site morbidity and increase the usefulness of the OCRFFF. Matched pairs of fresh human cadaveric radius bones were used in this study. Two study groups were designed. The first group was used to define the amount of strength lost after a typical bone graft harvest. The second group was designed to demonstrate how much torsional strength was regained by the application of an orthopedic reconstruction plate. Statistically significant results were obtained for both groups. In group 1, the strength of the cut bones compared with that of the unaltered bones was significantly decreased by 82% (P = 0.016). In group 2, the cut bones reinforced with a plate were 75% stronger (P = 0.002) than the bones that were only cut. Although the radius bone is significantly weakened by the harvest of a graft, much of this strength can be regained with plate fixation of the radius.

Biomechanical Phenomena↗

PubMed2000

Proline inhibits aggregation during protein refolding.

The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.

Animals↗

PubMed2000

Elucidation of the solution structure of cardiotoxin analogue V from the Taiwan cobra (Naja naja atra)--identification of structural features important for the lethal action of snake venom cardiotoxins.

The aim of the present study is to understand the structural features responsible for the lethal activity of snake venom cardiotoxins. Comparison of the lethal potency of the five cardiotoxin isoforms isolated from the venom of Taiwan cobra (Naja naja atra) reveals that the lethal potency of CTX I and CTX V are about twice of that exhibited by CTX II, CTX III, and CTX IV. In the present study, the solution structure of CTX V has been determined at high resolution using multidimensional proton NMR spectroscopy and dynamical simulated annealing techniques. Comparison of the high resolution solution structures of CTX V with that of CTX IV reveals that the secondary structural elements in both the toxin isoforms consist of a triple and double-stranded antiparallel beta-sheet domains. Critical examination of the three-dimensional structure of CTX V shows that the residues at the tip of Loop III form a distinct "finger-shaped" projection comprising of nonpolar residues. The occurrence of the nonpolar "finger-shaped" projection leads to the formation of a prominent cleft between the residues located at the tip of Loops II and III. Interestingly, the occurrence of a backbone hydrogen bonding (Val27CO to Leu48NH) in CTX IV is found to distort the "finger-shaped" projection and consequently diminish the cleft formation at the tip of Loops II and III. Comparison of the solution structures and lethal potencies of other cardiotoxin isoforms isolated from the Taiwan cobra (Naja naja atra) venom shows that a strong correlation exists between the lethal potency and occurrence of the nonpolar "finger-shaped" projection at the tip of Loop III. Critical analysis of the structures of the various CTX isoforms from the Taiwan cobra suggest that the degree of exposure of the cationic charge (to the solvent) contributed by the invariant lysine residue at position 44 on the convex side of the CTX molecules could be another crucial factor governing their lethal potency.

Amino Acid Sequence↗

PubMed2000

Shear augmented dispersion of a solute in a casson fluid flowing in a conduit.

The unsteady dispersion of a solute in a Casson fluid flowing in a conduit (pipe/channel) is studied using the generalized dispersion model of Gill and Sankarasubramanian. With this approach, the entire dispersion process is described appropriately in terms of a simple diffusion process with the effective diffusion coefficient as a function of time, in addition to its dependence on the yield stress of the fluid. The results are accurate up to a first approximation for small times, but verified with Sharp to be exact for large times. The model brings out mainly the effect of yield stress, or equivalently, the plug flow region on the overall dispersion process. It is found that the rate of dispersion is reduced (i.e., the effective diffusivity decreases) due to the yield stress of the fluid, or equivalently, the plug flow region in the conduit. Also, the effective diffusivity increases with time, but eventually attains its steady state value below a critical time [0.48(a2/Dm) for dispersion in a pipe and 0.55(a2/Dm) for dispersion in a channel-the critical transient time for a Newtonian fluid-where "a" is the radius of the pipe and Dm is the molecular diffusivity]. At steady state, for dispersion in a pipe with the plug flow radius one tenth of the radius of the pipe, the effective diffusivity is reduced to about 0.78 times of the corresponding value for a Newtonian fluid at equivalent flow rates; for dispersion in a channel, the reduction factor is about 0.73 confirming the earlier result of Sharp. Further, the location of the center of mass of a passive species over a cross section is found to remain unperturbed during the course of dispersion and for different values of the plug flow parameter (i.e., the yield stress of the fluid). The study can be used as a starting first approximate solution for studying the dispersion in the cardiovascular system or blood oxygenators.

Biomechanical Phenomena↗

PubMed2000

Aminopeptidase-A. I. CDNA cloning and expression and localization in rat tissues.

Aminopeptidase-A (APA) is an ectoenzyme that selectively hydrolyzes acidic residues from the amino terminus of oligopeptides, including biologically active [Asp(1)]ANG II and [Asp(1)]CCK-8. We sought to characterize rat APA by cDNA cloning and expression and to determine its tissue distribution by in situ hybridization and immunohistochemistry. Sequence analysis of overlapping cDNA clones isolated from rat kidney cDNA libraries indicated that the full-length cDNA encoded a 945-amino acid protein with a predicted molecular mass of 108 kDa; the size was confirmed by in vitro translation of a full-length cDNA construct. Transient transfection of the full-length cDNA construct in mammalian cells yielded a protein approximately 140 kDa in size, a size that agrees with the immunoblots of APA from rat tissue and is consistent with APA being known as a glycosylated protein. Tissue APA activity and mRNA expression were highest in the kidney and ileum. Localization of APA by in situ hybridization and immunohistochemistry indicated that, with the exception of the kidney and ileum, where APA was localized to the luminal brush border of proximal tubules and enterocytes, respectively, APA was associated with either capillaries or the lining of sinusoids. Areas known to be physiological targets for ANG II, including glomeruli, the zona glomerulosa, and anterior pituitary, had high levels of APA. The localization pattern suggests that APA may subserve multiple functions, i.e., a generalized role in peptide scavenging and perhaps a more specific role in metabolism of circulating or locally produced ANG II or CCK-8.

Amino Acid Sequence↗

PubMed2000

Aminopeptidase-A. II. Genomic cloning and characterization of the rat promoter.

Aminopeptidase-A (APA) has a widespread tissue distribution consistent with a role in the metabolism of circulating or locally produced ANG II or CCK-8. APA is also highly expressed in pre-B lymphocytes, but its role in lymphoid cell development is unknown. To begin to understand the basis for cell-specific regulation of APA expression, we sought to clone and characterize the rat gene promoter. Screening of a rat genomic library with a partial rat APA cDNA resulted in isolation of a 12-kb clone found to contain the first exon and >3 kb of 5'-flanking sequence. Primer extension of rat kidney mRNA indicated that the major transcription start site was 312 bp upstream of the translation start codon and 22 bp downstream from a TATA box. Constructs containing portions of the 5'-flanking region placed upstream of a chloramphenicol acetyltransferase reporter gene indicated that expression was cell specific and that high activity could be obtained with constructs containing as little as 110 bp of 5'-flanking region sequence. We further identified an upstream regulatory element between -1063 and -348 that suppressed transcription in a cell-specific manner. This element (termed upstream suppressor of APA, or USA) also suppressed transcription of a heterologous promoter. These results indicate that the organization and regulation of the rat APA is not consistent with it being a housekeeping gene and further suggest that rat APA gene transcription might be regulated through the presence of a novel strong upstream suppressor element.

Aminopeptidases↗

PubMed2000

Osteocutaneous radial forearm free flaps. The necessity of internal fixation of the donor-site defect to prevent pathological fracture.

BACKGROUND: Osteocutaneous radial forearm free flaps have fallen from favor due to pathological fractures of the radius. The purposes of this study were to propose a means to decrease the rate of pathological fracture by prophylactic fixation of the donor-site defect and to evaluate this technique biomechanically. METHODS: Two groups of ten matched pairs of fresh-frozen cadaveric radii were harvested. In Group 1, an eight-centimeter length of radius comprising 50 percent of the cross-sectional area of the bone was removed to simulate an osteocutaneous radial forearm donor-site defect. This defect was created in one member of each pair, with the other bone in the pair left intact. In Group 2, both members of the ten matched pairs of radii had identical defects created as previously described. However, one radius in each pair had a twelve-hole, 3.5-millimeter dynamic compression plate placed across the segmental defect. In each group, five matched pairs were tested to failure in torsion and five matched pairs were tested to failure in four-point bending. RESULTS: In Group 1, the intact radius was a mean of 5.7 times stronger in torsion and 4.2 times stronger in four-point bending than the radius with the segmental resection. In Group 2, the radius that was ostectomized and fixed with a plate was a mean of 4.0 times stronger in torsion and 2.7 times stronger in four-point bending than the ostectomized radius. CONCLUSIONS: Removal of an eight-centimeter segment from the radius dramatically decreased both torsion and bending strength. Application of a plate over the defect in the radius significantly restored the strength of the radius (p = 0.01).

Biomechanical Phenomena↗

PubMed1999

Binding of nucleotide triphosphates to cardiotoxin analogue II from the Taiwan cobra venom (Naja naja atra). Elucidation of the structural interactions in the dATP-cardiotoxin analogue ii complex.

Snake venom cardiotoxins have been recently shown to block the enzymatic activity of phospholipid protein kinase and Na+,K+-ATPase. To understand the molecular basis for the inhibitory effects of cardiotoxin on the action of these enzymes, the nucleotide triphosphate binding ability of cardiotoxin analogue II (CTX II) from the Taiwan cobra (Naja naja atra) venom is investigated using a variety of spectroscopic techniques such as fluorescence, circular dichroism, and two-dimensional NMR. CTX II is found to bind to all the four nucleotide triphosphates (ATP, UTP, GTP, and CTP) with similar affinity. Detailed studies of the binding of dATP to CTX II indicated that the toxin molecule is significantly stabilized in the presence of the nucleotide. Molecular modeling, based on the NOEs observed for the dATP.CTX II complex, reveals that dATP binds to the CTX II molecule at the groove enclosed between the N- and C-terminal ends of the toxin molecule. Based on the results obtained in the present study, a molecular mechanism to account for the inhibition of the enzymatic activity of the phospholipid-sensitive protein kinase and Na+,K+-ATPase is also proposed.

Circular Dichroism↗

PubMed1999

p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.

Binding Sites↗

PubMed1999

Flow in a catheterized curved artery with stenosis.

The fluid mechanics of blood flow in a catheterized curved artery with stenosis is studied through a mathematical analysis. Blood is modelled as an incompressible Newtonian fluid and the flow is assumed to be steady and laminar. An approximate analytic solution to the problem is obtained through a double series perturbation analysis for the case of small curvature and mild stenosis. The effect of catheterization on various physiologically important flow characteristics (i.e. the pressure drop, impedance and the wall shear stress) is studied for different values of the catheter size and Reynolds number of the flow. It is found that all these flow characteristics vary markedly across a stenotic lesion. Also, increase in the catheter size leads to a considerable increase in their magnitudes. These results are used to obtain the estimates of increased pressure drop across an arterial stenosis when a catheter is inserted into it. Our calculations, based on the geometry and flow conditions existing in coronary arteries, suggest that, in the presence of curvature and stenosis, and depending on the value of k (ratio of catheter size to vessel size) ranging from 0.1 to 0.4, the pressure drop increases by a factor ranging from 1.60 to 5.16. But, in the absence of curvature and stenosis, with the same range of catheter size, this increased factor is about 1.74-4.89. These estimates for the increased pressure drop can be used to correct the error involved in the measured pressure gradients using catheters. The combined effects of stenosis and curvature on flow characteristics are also studied in detail. It is found that the effect of stenosis is more dominant than that of the curvature. Due to the combined effect of stenosis, curvature and catheterization, the secondary streamlines are modified in a cross-sectional plane. The insertion of a catheter into the artery leads to the formation of increased number of secondary vortices.

Arteries↗