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PubMed1984

Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

Aging↗
PubMed1996

Characterization of a large conductance, cation-selective channel from sea urchin eggs that is sensitive to sulfhydryl reducing agents.

Vesicles containing large conductance cation selective channels were isolated from sea urchin (Strongylocentrotus purpuratus) eggs. Addition of the vesicles to one side of lipid bilayer led to the rapid appearance of 200 or more identical channels. These channels would then inactivate within 2 to 10 min. The inactivation could be prevented by the addition of sulfhydryl reducing agents (e.g., dithiothreitol or glutathione) to the cis side of the membrane. Only one channel type is present. The channel is cation selective, with a conductance of 572 ps in symmetrical 0.5 M KCl. The relative cation selectivity is K (1.0) > Cs (0.53) approximately < Na (0.52) > Li (0.2). The permeability ratio (Px/Pk) is 1.37 (Li) > 1.27 (Na) > 0.57 (Cs). Most organic cations (choline, tetraethylamine, tetrabutylamine, gallamine, lysine, histidine, arginine, etc.) and multivalent cations (La+3, alkali earth family, Zn+2, Eu+3, etc.) produced a significant channel block. The highest observed affinity was for La+3 which produced a 50% decrease in conductance in 500 mM KCl at a concentration of 8 microM. The biophysical properties of this channel are similar to those of a non-selective channel found in ascidian egg plasma membrane (Dale & DeFelice, 1984). A soluble extract of the egg supernatant can also prevent the inactivation of the channels. Using deactivated channels reconstituted into a planar lipid bilayer as an assay, this factor was partially purified. It is heat and acetone stable with a molecular weight of between 10 and 20 K. One of the major bands remaining in the purest fraction cross reacted with antibodies raised against E. coli thioredoxin.

Animals↗
PubMedDate not supplied

Effect of reducing agents on proteolytic and keratinolytic activity of enzymes of Microsporum gypseum.

The effect of sodium sulphite, cysteine, glutathione, mercaptoethanol and dithioerythritol (0.1-10 mmol l-1) on the activity of proteases of Microsporum gypseum was studied using azocasein, cross-linked bovine serum albumin and keratin as substrates. With the substrate without disulphide bonds (casein) no stimulation was found, and reducing agents inhibited proteolysis in most cases. With the remaining two substrates, all substances enhanced the activity of proteases probably through the cleavage of the substrate disulphide bonds. Sulphite was more effective than the four used thiols and enhanced the activity against serum albumin up to 3.2 times and against keratin up to 2.9 times. Using sulphitolysed sheep wool, keratinolytic activity increased after sulphitolysis of more than 20% of disulphide bonds. With the fully sulphitolysed wool the activity increased 43 times. The obtained results support the author's hypothesis on keratin degradation by sulphite excretion prior to attack by fungal proteases. Stimulation of proteolysis and keratinolysis by cleavage of disulphide bonds is not specific for dermatophytic proteases because trypsin and pronase behaved similarly in the experiments.

Animals↗
PubMed2003

Identification of genes in thyrocytes regulated by unfolded protein response by using disulfide bond reducing agent of dithiothreitol.

Disulfide bonds are formed between the sulfhydryl groups in two cysteine residues of a protein. The formation of these bonds is necessary for the proper folding of a protein into its active three-dimensional form. In this study, the genes associated with disulfide bond formation of proteins from the rat thyroid cell line, FRTL-5 cell, were investigated using disulfide bond reducing agent of dithiothreitol (DTT), which prevented disulfide formation of newly synthesized proteins. The expression of six genes, they being the cAMP phosphodiesterase 7A1, neuronal cell death inducible putative kinase (NIPK), cytosolic LIM protein (Ajuba), Eker, early growth response 1 and the ferritin heavy chain, was specifically enhanced under both reductive conditions and various endoplasmic reticulum (ER) stresses inducing drugs such as Brefeldin A (BFA), calcium ionophore A23187 (A23187) and tunicamycin. These results suggest that a suitable redox environment is necessary for the correct disulfide bond conformation in thyrocytes in a complex system.

Animals↗
PubMed1977

Interaction of Treponema pallidum (Nichols strain) with cultured mammalian cells: effects of oxygen, reducing agents, serum supplements, and different cell types.

Cultured mammalian cells extend the time of survival of Treponema pallidum (Nichols strain). Various parameters that have been previously shown to enhance treponemal survival in vitro were examined for influences on the interaction of T. pallidum with cultured cells. With cells derived from normal rabbit testes, the time of retention of treponemal virulence was extended in an atmosphere containing reduced concentrations of oxygen. Glutathione and cysteine, when added to the basal tissue culture medium, prolonged treponemal survival. In an assessment of various tissue culture medium supplements, normal rabbit serum was equivalent to fetal bovine serum and superior to bovine serum albumin fraction V (BSA), fatty acid-poor BSA, and lipid-pooed for TRK-2, HSE, NRK, and C6 cells. Dithiotreitol, as an additional reducing agent, sharply enhanced treponemal survival. With SF1Ep NBL-11 cells and basal tissue culture medium containing glutathione, cysteine, and dithiothreitol, in an atmosphere of approximately 3% oxygen, T. pallidum was maintained without detectable decreases in the number of virulent organisms for 6 days.

Blood↗
PubMed1984

Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents.

The C-8 position of deoxyguanosine (dGuo) was hydroxylated by ascorbic acid in the presence of oxygen (O2) in 0.1 M phosphate buffer (pH 6.8) at 37 degrees C. Addition of hydrogen peroxide (H2O2) remarkably enhanced this hydroxylation. The Udenfriend system [ascorbic acid, FeII, ethylenediaminetetraacetic acid (EDTA) and O2] was also effective for hydroxylation of dGuo in high yield. Guanine residues in DNA were also hydroxylated by ascorbic acid. Other reducing agents, such as hydroxylamine, hydrazine, dihydroxymaleic acid, sodium bisulfite and acetol, were also effective for the hydroxylation reaction, as were metal-EDTA complexes (FeII-, SnII-, TiIII-, CuI-EDTA). An OH radical seemed to be involved in this hydroxylation reaction in most of the above hydroxylating systems, but another reaction mechanism may also be involved, particularly when dGuo is hydroxylated by ascorbic acid alone or ascorbic acid plus H2O2. The possible biological significance of the hydroxylation of guanine residues in DNA in relation to mutagenesis and carcinogenesis is discussed.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1981

Differential inhibition of rat liver DNA polymerases in vitro by direct-acting carcinogens and the protective effect of a thiol reducing agent.

The direct-acting carcinogens acetoxyacetylaminofluorene, methylnitrosourea, and N-methyl-N'-nitro-N-nitrosoguanidine were tested for their ability to inhibit rat liver DNA polymerase-alpha, -beta, and -gamma activity in vitro. DNA polymerase-alpha was the most sensitive, polymerase-beta was the most resistant, and polymerase-gamma exhibited an intermediate response. When the reactions were reassayed in the presence and absence of dithiothreitol, a thiol reducing agent, it was shown that the inhibition by carcinogens was generally reversible with increasing dithiothreitol, except that polymerase-beta recovered only 80-90% of control values. These and binding data suggest that DNA polymerase-beta, the putative repair enzyme, is highly resistant to carcinogen damage. This resistance may contribute to the retention of normal function and fidelity of the repair enzyme during carcinogen exposure in vivo and to a normal cellular repair.

Acetoxyacetylaminofluorene↗
PubMed1986

Conformational studies of lipoprotein B and apolipoprotein B: effects of disulfide reducing agents, sulfhydryl blocking agent, denaturing agents, pH and storage.

The purposes of this study were to establish the role of disulfide linkages in the secondary structure of apolipoprotein B, to investigate the effects of sulfhydryl blocking agents, denaturing agents, pH and storage on the conformation of apolipoprotein B and lipoprotein B, and to compare the conformation of water-soluble apolipoprotein B in the presence and absence of its lipids by using circular dichroism. Fresh lipoprotein B examined in Tris/EDTA at pH 9.0, 7.3 and 2.7 exhibited alpha-helical content of 24.4, 26.7 and 26.9%, and beta-pleated sheet 25.1, 15.4 and 18.0%, respectively. The carboxymethylated (CM-) lipoprotein B had similar alpha-helical contents, and lower contents of beta-sheets. Storage of lipoprotein B resulted in marked change of beta-sheets and gradual decrease in alpha-helical structure, in spite of the preventive measures taken for lipid peroxidation and proteolytic degradation. Exposure of apolipoprotein B to 6 M guanidine X HCl led to a complete disappearance of the alpha-helix with an increase in the beta-sheets to 35-40%, irrespective of the use of disulfide-reducing agents. By substituting 6 M urea for guanidine X HCl, the alpha-helical contents for both CM- and reduced CM-apolipoprotein B increased up to 7-9% with a concomitant decrease in beta-structure. When urea was replaced with aqueous buffers, these apolipoprotein B preparations regained their alpha-helical contents (25-27%) to the full extent originally present in the parent lipoprotein samples. No difference was observed between the secondary structure of CM- and reduced CM-apolipoprotein B. Furthermore, the conformation of apolipoprotein B did not vary with pH when pH was changed from 2.7 to 9.0. These results suggest that (1) the conformation of apolipoprotein B is more stable with respect to pH in the absence of lipids than in their presence, (2) intramolecular disulfide linkages play an insignificant role in the conformation of apolipoprotein B, and (3) the changes in alpha-helix structure of lipoprotein B or CM-lipoprotein B due to delipidization and denaturation are reversible.

Apolipoproteins B↗
PubMed1976

The dissociation of factor VIII by reducing agents, high salt concentration and affinity chromatography.

Incubation of a factor VIII-rich fraction of plasma with a high concentration of salt confirmed the production of both high (HMW) and low (LMW) molecular weight factor VIII clotting activity (FVIIIC) as determined by agarose gel filtration but with considerable overlap. The electrophoretic mobility of factor VIII related protein (FVIIIRP) detected by precipitating rabbit antiserum was not affected by this treatment and LMW FVIIIC devoid of FVIIIRP was apparently produced. At low concentration the reducing agent dithiothreitol (DTT) altered the electrophoretic mobility of FVIIIRP. At higher concentrations it altered both its mobility and antigenicity and an LMW FVIIIRP was produced. Contrary to the findings of other workers no LMW FVIIIC devoid of FVIIIRP was produced. In further studies factor VIII-rich plasma fraction was treated with sepharose beads to which had been coupled a non-coagulation inhibitory precipitating rabbit antibody to FVIIIRP. Both FVIIIRP and FVIIIC were taken up by the beads but after elution with 1.5 M NaCl, FVIIIC of LMW and devoid of FVIIIRP was selectively removed. Antisera raised to LMW FVIIIC produced with 1.5 M NaCl either by the gel filtration or affinity chromatography methods inhibited FVIIIC and precipitated with HMW factor VIII-rich fractions. The results were consistent with the possibility that factor VIII clotting activity and FVIIIRP exist in plasma as a non-covalently bound complex.

Antigens↗
PubMed1994

Thiol-reducing agents and calcium perturbants alter intracellular sorting of immunoglobulin M.

The secretory form of IgM (sIgM) undergoes developmentally regulated intracellular sorting and transport, as demonstrated by the distinct assembly patterns and intracellular fate exhibited by its mu heavy chain (microseconds). In the 38C B lymphocytes, microseconds-containing monomers are retained and degraded intracellularly, whereas in the 38C-derived D2 hybridoma, microseconds-containing polymers are secreted. Here we show that sorting of sIgM is impaired in the presence of the thiol-reducing agent beta-mercaptoethanol or when cellular calcium sequestration is perturbed either with the Ca2+ ionophore A23187 or with thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase. Under these conditions, sIgM evades retention/degradation in the 38C cells, resulting in its enhanced secretion. Conversely, in the D2 cells, secretion is strongly attenuated, and sIgM is partly degraded. Both cell types secrete unusually processed sIgM, which is completely resistant to endoglycosidase H, unlike the partially sensitive sIgM secreted in the usual manner, indicating terminal glycosylation of all carbohydrate moieties of microseconds. Moreover, secretion is no longer restricted to fully assembled polymeric sIgM, and in both cell types under Ca2+ perturbation preferentially hemimeric and monomeric assembly intermediates are detected in the medium. Our results suggest that the intracellular fate of sIgM is collectively determined by several sorting events that confer sIgM retention/degradation, ensure sIgM secretion from D2 cells, and prevent the arrival of assembly intermediates to the cell surface. All of these sorting events appear to require high Ca2+ concentration and oxidizing thiol redox state, the conditions that prevail in the lumen of the endoplasmic reticulum. Thus, thiol and calcium are implicated as modulators of intracellular traffic.

Animals↗
PubMed1984

Murine retrovirus Pr65gag forms a 130K dimer in the absence of disulfide reducing agents.

Gazdar-murine sarcoma virus (Gz-MSV) particles, obtained from tissue culture fluids of chronically infected HTG-2 hamster cells are immature in morphology and contain uncleaved Pr65gag as the predominant protein (greater than 95% Coomassie blue stain) (A. Pinter and E. deHarven, 1979, Virology 99, 103-110; Y. Yoshinaka and R. B. Luftig, 1982, Virology 118, 380-388). When Gz-MSV particles are disrupted in 1% sodium dodecyl sulfate (SDS) and then analyzed by SDS-polyacrylamide gel electrophoresis (PAGE) in the absence of reducing agents, such as beta-mercaptoethanol (beta-MSH) almost half of the Pr65gag Coomassie blue-stained band is detected as a band at a Mr of 130K. Electrophoretic blotting studies with monospecific antisera against MuLV p30, p15, p12, and p10 showed that the 130K band cross-reacted with all four antigens suggesting that it was a dimer of Pr65gag. Two-dimensional (2D) SDS-PAGE where the first dimension was run under nonreducing conditions and the second with beta-MSH, supported the contention that the 130K band was a dimeric complex of Pr65gag. One also saw minor amounts of a 260K and higher polymeric forms of Pr65gag on the SDS gels, suggesting that polymeric forms may exist as well. When 32P-labeled Gz-MSV particles obtained by in vivo labeling of infected HTG-2 cells with [32P]PPi were electrophoresed on SDS-PAGE, only 10% of the 32P label was detected at the 130K position. In contrast, 30% of the Coomassie blue-stained Pr65gag material was found at 130K on the 2D gels. This suggests that unphosphorylated Pr65gag is more likely to participate in dimer formation than phosphorylated Pr65gag. Pr65gag of Moloney murine leukemia virus (M-MuLV), which is present as a minor (5% of stain) protein band on SDS-PAGE also showed 130K dimers. Further, in beta-MSH-deficient SDS preparations of Gz-MSV, electrophoresed after trypsin treatment, a 32K band that stained with p15, but not p10, p12, nor p30, antisera was observed. If beta-MSH was added, this band was no longer present. Thus Pr65gag dimerization in immature MuLV particles appears to at least involve the p15 region of the polyprotein. Since p15 is an extremely hydrophobic protein, formation of Pr65gag dimers may occur when virion precursor proteins are brought to the cell membrane during virus assembly.

Animals↗
PubMed1983

Activation of bronchial mucin proteolysis by 4-aminophenylmercuric acetate and disulphide bond reducing agents.

High molecular weight bronchial glycoproteins, as nearly native as possible, were treated with either 2-mercaptoethanol or 4-aminophenylmercuric acetate (APMA): analytical electrophoresis revealed that a decrease in molecular weight of glycoproteins coincided with the disappearance of some proteins associated with high molecular weight bronchial glycoproteins. These modifications were not observed if high molecular weight bronchial glycoproteins were incubated with paramethylsulphonyl fluoride and EDTA, two synthetic protease-inhibitors, prior to 2-mercaptoethanol or APMA action. These data suggest that protease-antiprotease complexes are associated with bronchial mucins and that reducing agents or APMA activate proteases.

Bronchi↗
PubMed1990

Reducing agents interfere with the detection of lettuce necrotic yellows virus in infected plants by immunoblotting with monoclonal antibodies.

A procedure is described for the detection of lettuce necrotic yellows virus (LNYV) nucleocapsid protein (N) or envelope glycoprotein (G) by immuno-blotting with their respective monoclonal antibodies. The antigens can be detected in 1-10 mg of fresh tissue from systemically infected Nicotiana glutinosa leaves showing prominent symptoms. The composition of the extraction buffer played a crucial role in the recovery of antigenically active proteins. Procedures involving tissue extraction in the presence of the reducing agents 2-mercaptoethanol (2-ME) or dithiothreitol (DTT) failed to detect either the N or G antigen. For optimum detection of the N or G antigens, leaf tissue was ground with 10 mM phosphate buffer, pH 7.6 (PB), containing 3% (w/v) sodium dodecyl sulphate (SDS) and 1 mM of the protease inhibitor N-p-tosyl-L-lysine chloromethyl ketone (TLCK). The extract was then mixed with an equal volume of dissociation buffer containing 2-ME before electrophoresis and immunoblotting.

Animals↗
PubMed1983

Destruction of antibody idiotopes with ultra-low concentrations of reducing agents.

The nature of the idiotopes present on F(ab')2 fragments prepared from rabbit anti-micrococcal carbohydrate antibodies and the loss of idiotypic reactivity of these F(ab')2 fragments upon iodination were examined. Rabbit anti-micrococcal idiotopes were shown to be exquisitely sensitive to treatment with very low concentrations of sodium metabisulfite or 2-mercaptoethanol. The treatment destroyed anti-micrococcal idiotopes, as shown by the loss of idiotopes on F(ab')2 fragments after reduction; the allotype epitopes and the antigen binding capacity of the F(ab')2 fragments were unaffected. The destruction of the idiotopes by very low concentrations of reducing agents indicated that an extremely labile disulfide bond is involved in the structure of the idiotope or in the maintenance of the conformation of the anti-micrococcal idiotopes. Identical reduction-sensitive anti-micrococcal idiotopes have been demonstrated in a number of related outbred rabbits, and in each case they induced a natural auto-anti-idiotype (AAI) antibody response. Recognition of the existence of these reduction-sensitive idiotopes and their properties could provide a basis for further study of these idiotopes and may lead to a better understanding of the idiotope network.

Animals↗
PubMed1981

Spontaneous rosette formation of pig and guinea pig thymocytes and peripheral blood lymphocytes: influence of proteases, oxidising and reducing agents, cytochalasin B and carbohydrates.

Spontaneous rosette formation (SRF) of pig and guinea pig thymocytes (Th) and thymus derived peripheral blood lymphocytes (PTL) was tested under different experimental conditions. Treatment with different proteases (trypsin, chymotrypsin, protease type VII) showed that SRF of pig Th and PTL is inhibited to a much higher extent than that of guinea pig Th and PTL. Cytochalasin B (CB) inhibited SRF of PTL of both species to a higher degree as compared to Th. Different carbohydrates neither influenced SRF of Th nor of PTL in both species indicating that simple carbohydrates are not the recognized component of SRF receptors. Treatment with oxidising and reducing agents did not influence SRF.

Animals↗
PubMed1971

Increase in osmiophilia of axonal membranes of crayfish as a result of electrical stimulation, asphyxia, or treatment with reducing agents.

Certain axonal membranes of crayfish abdominal nerve cord display ultrastructural changes if the axons are fixed, during electrical stimulation, by aldehydes followed by osmium. Such changes are characterized by an increase in electron opacity and thickness of the unit membranes' dense strata in the axon surface, endoplasmic reticulum, and outer mitochondrial membranes. The electron opacity completely disappears if the sections are treated with hydrogen peroxide solutions. This suggests that the changes represent an increase in the membranes' reactivity for osmium. An unmasking of SH groups could explain such increased osmiophilia, since SH groups are very reactive with osmium, while disulfide bonds are considerably less reactive. This hypothesis was tested by treating control, glutaraldehydefixed nerve cords with disulfide reducing agents. In these preparations an increase in electron opacity and thickness was observed to be localized in the same axonal membranes which reacted as a result of electrical stimulation. The phenomenon did not appear if the SH groups were blocked by maleimide or N-ethylmaleimide before treatment with osmium. These findings seem to suggest that certain axonal membranes of crayfish contain proteins rich in sulfur whose SH groups are unmasked as a result of electrical stimulation. In preliminary experiments an increase in osmiophilia localized in the same membranes with the same characteristics and distribution was observed also in axons from nerve cords asphyxiated either in vitro or in the living animal.

Aldehydes↗
PubMed2000

Effects of Divalent Cations and Disulfide Bond Reducing Agents on Specific Binding of Growth Hormone to Liver Membrane Receptors from Snakehead Fish (Ophiocephalus argus, Cantor).

Divalent cations, Ca(2 ), Mg(2 ) and Mn(2 ) enhance the binding of bream growth hormone (brGH) to snakehead fish liver membrane, and their optimum concentration was found to be 8 12 mmol/L, at which Ca(2 ), Mg(2 ) and Mn(2 ) could increase, respectively, the specific binding to 230%, 180%, and 200%, compared with the binding in the absence of ions. The Eadie-Scatchard plot was used for the dynamic analysis of the Ca(2 ) binding site. A low affinity Ca(2 ) binding site was found in the GH-receptor complex with K(m)=0.384 mmol/L, and the affinity constant (K(a)) was increased from 1.045x10(9) L.mol(-1) to 1.295x10(9) L.mol(-1) by the addition of 10 mmol/L CaCl(2). The effects of disulfide bond reducing agents, DTT and ME, on (125)I-brGH binding to growth hormone receptor (GHR) on snakehead fish liver memebrane were also analyzed. The addition of 0.1 20 mmol/L DTT or 0.01% 1% ME to the radioreceptor assay system caused a significant dose dependent increase in the specific binding for (125)I-brGH. In the presence of 0.8 mmol/L DTT or 0.08% ME, the specific binding of (125)I-brGH was increased from 10.2% to 15.5% and 13.2% respectively, and the affinity constant was also increased from 1.265x10(9) L.mol(-1) to 2.185x10(9) L.mol(-1) and 1.625x10(9) L.mol(-1), respectively but no changes in the binding capacity were observed. Further studies showed that the effects of reductants on the specific binding of brGH were due in part to the ligand itself and in part to GHR. In addition, it was observed that one of the three disulfide bonds of brGH could be reduced by 0.8 mmol/L DTT.

Journal Article↗
PubMed2000

Neonatal treatment with beta-cell stimulatory agents reduces the incidence of diabetes in BB rats.

The aim of the study was to investigate whether various beta-cell stimulatory drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn BB rats were treated twice daily for 6 days and diabetes development was observed during the following 200-day study period. Compared to a diabetes incidence of 63.8% in 163 control BB rats which received saline or were untreated, the percentage of experimental BB rats that developed diabetes was as follows in the different subgroups: arginine-glucose: 47% (n = 73, p < 0.02); glucagon: 37% (n = 93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline-glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not superior to the shorter neonatal treatment. Histological examination revealed a higher degree of insulitis in diabetic than in non-diabetic animals but no difference according to the kind of treatment was observed. Finally, we found that the diabetes incidence in BB rats was higher in the first litter compared to subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell stimulatory agents reduces diabetes incidence in BB rats. The theory behind the study, that the treatment accelerates beta-cell maturation leading to increased immunological tolerance towards beta cells, is discussed.

Animals↗