Frequency of glucose-6-phosphate dehydrogenase deficiency in sickle-cell disease. A study in Saudi Arabia

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 50 Hb S homozygotes (SS) and 98 Hb S heterozygotes (AS) was determined and compared with the frequency obtained in individuals with normal haemoglobin (AA). The observed number of SS patients with G-6-PD deficiency was significantly greater than the expected value (p less than 0.05). The frequency of G-6-PD deficiency in AA, AS and SS was found to be 0.172, 0.214 and 0.420, respectively. A statistically significant increase of G-6-PD deficiency was apparent in the Saudi sicklers. The possibility that G-6-PD deficiency and Hb S gene interact, influencing the survival of the carriers of these genetic abnormalities, is discussed.     

Primate red cell enzymes: glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase

Glucose-6-phosphate dehydrogenase (E. C.: 1.1.1.49) phenotypes and 6-phosphogluconate dehydrogenase (E. C.: 1.1.1.44) phenotypes were determined by starch-gel electrophoresis of red cell hemolysates of Galago crassicaudatus subspp., Propithecus verreauxi, Lemur spp., Hapalemur griseus, and Macaca mulatta. A single glucose-6-phosphate dehydrogenase (G6PD) phenotype was found in each species. A single 6-phosphogluconate dehydrogenase (6PGD) phenotype was found in Lemur spp., Hapalemur griseus, and Galago crassicaudatus argentatus. In a group of six Propithecus verreauxi, three 6PGD phenotypes, PGD A, PGD AB, and PGD B, were found. Three phenotypes, PGD A, PGD AB, and PGD B, were found in 38 G. c. crassicaudatus. The three phenotypes in each species are apparently the products of two codominant autosomal alleles, PGD^A and PGD^B. The frequency of PGD^A in G. c. crassicaudatus is 0.263. A population of 260 free-ranging macaques displays a polymorphism at the 6PGD locus. Three phenotypes, PGD A, PGD AB, and PGD B, were found. These also appear to be controlled by two codominant autosomal alleles, PGD^A and PGD^B the frequency of PGD^A = 0.913. Additional analysis of three well-defined troops within the macaque population indicated that there are no significant differences between the troops or within the population at the 6PGD locus.     

G-6-PD Jalisco and G-6-PD Morelia: Two new Mexican variants

Summary Two new G-6-PD variants designated G-6-PD Jalisco and G-6-PD Morelia were identified in two unrelated Mexican families. An additional G-6-PD variant was found in each family: G-6-PD trinacria and G-6-PD A^-. In both families compound heterozygotes were identified. G-6-PD Jalisco and G-6-PD Morelia belong to Classes 3 and 4, respectively. G-6-PD Morelia is the first variant from its class with a high Km for NADP and a low Ki for NADPH.     

Activities of Glucose-6-phosphate, 6-phosphogluconate,and Isocitrate Dehydrogenases from Leishmania donovani Cultivated at 25 and 37 C*

SYNOPSIS. The activities of glucose-6-phosphate dehydrogenase (G-6-PD) (EC No. 1.1.1.49), 6-phosphogluconate dehydrogenase (PGD) (EC No. 1.1.1.44), and isocitrate dehydrogenase (ICD) (EC No. 1.1.1.42) from promastigotes of Leishmania donovani strain 3S grown at 25 C in modified Tobie's (mT) medium and from promastigotes of the 37 C-adapted substrain of this strain cultivated in the mT at 37 C were assayed at 25 and 37 C. At 25 C ICD from both the strain and the substrain had the highest, and PGD, the lowest activity; the activity of G-6-PD was intermediate, but much closer to that of ICD. Irrespective of the temperature of the assay, the activities of G-6-PD and ICD from the 37 C substrain were significantly higher than those of these enzymes from the parental strain; however, the activity of PGD from the 25 C strain was slightly higher than that of this dehydrogenase from the 37 C-adapted stock. No significant activity losses of G-6-PD and ICD from either the strain or the substrain were noted after incubation of the extracts in the presence of 0.25 M sucrose at 37 C for 2 hr. PGD was unstable in such extracts, but it could be rendered stable by the addition of 4 mM 6-phosphogluconate. G-6-PD was the least and ICD the most dependent on Mg²⁺ ions. In the 15–25 C range, the Q₁₀ values of the enzymes from the 25 C strain were 2.83, 2.5, and 2.63 for G-6-PD, PGD, and ICD, respectively. These values for the respective enzymes in the 25–35 C range were 2.06, 1.67, and 1.62. The Q₁₀ values of the enzymes from the 37 C substrain in the 15–25 C range were 2.06 for G-6-PD, 3.25 for PGD, and 2.77 for ICD; in the 25–35 C range, the corresponding values were 1.67, 1.46, and 1.83. Cultivation of the 37 C substrain at 25 C was accompanied by a drop in G-6-PD and ICD activities.     

Zur transspezifischen Variabilität der Glucose-6-Phosphatdehydrogenase (E.C.: 1.1.1.49) der Primaten

Zusammenfassung Bei subhumanen Primaten können auf Grund ihrer unterschiedlichen Wandergeschwindigkeit in der Elektrophorese fünf verschiedene Glucose-6-Phosphatdehydrogenase-Varianten nachgewiesen werden. Die Verteilung dieser Varianten wurde ermittelt.

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Transspecific variability of glucose-6-phosphate dehydrogenase (E.C.: 1.1.1.49) in Primates

Summary On the basis of their different electrophoretic mobility five Glucose-6-phosphate dehydrogenase variants are detectable in subhuman Primates: G-6-PD D, G-6-PD C, G-6-PD B, G-6-PD E, G-6-PD F. Their distribution in 428 individuals was estimated.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Polymorphism of erythrocyte G-6-PD in the baboon

Blood samples from several populations of baboons (genus Papio) were examined for G-6-PD variants. Several G-6-PD phenotypes were detected by starch gel electrophoresis. The so-called fast variant phenotypes of G-6-PD in baboons differ from human variant phenotypes in several physicochemical constants.     

Blood groups and types,hemoglobin variants,and G-6-PD deficiency among Abu Dhabians in the United Arab Emirates

Some erythrocyte genetic factors were studied in the indigenous population of Abu Dhabi, the capital of the United Arab Emirates, on the south-eastern coast of the Arabian peninsula. Determinations carried out included blood groups and types ABO, MNS, Rh_o, KkJs^a, Fy^aFy^b, P₁, Le^a, Vel^a, hemoglobin variants, and screening for G-6-PD deficiency. Prevalence of most blood groups and types harmonized with that among neighboring Arabs and some Arabs elsewhere. The MS and NS gene complexes were noticeably high. African admixture was expressed by the presence of Js^a and Hb S and large numbers of Fy. G-6-PD deficiency was rather high.     

Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart

The capacity of the oxidative pentose phosphate pathway (PPP) in the heart is limited, since the activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway, is very low. Two mechanisms are involved in the regulation of this pathway. Under normal conditions, G-6-PD is inhibited by NADPH. This can be overcome in the isolated perfused rat heart by increasing the oxidized glutathione and by elevating the NADP⁺/NADPH ratio. Besides this rapid control mechanism, there is a long-term regulation which involves the synthesis of G-6-PD. The activity of G-6-PD was elevated in the rat heart during the development of cardiac hypertrophy due to constriction of the abdominal aorta and in the non-ischemic part of the rat heart subsequent to myocardial infarction. The catecholamines isoproterenol and norepinephrine stimulated the activity of myocardial G-6-PD in a time- and dose-dependent manner. The isoproterenol-induced stimulation was cAMP-dependent and due to increased new synthesis of enzyme protein. The G-6-PD mRNA was elevated by norepinephrine. As a consequence of the stimulation of the oxidative PPP, the available pool of 5-phosphoribosyl-l-pyrophosphate (PRPP) was expanded. PRPP is an important precursor substrate for purine and pyrimidine nucleotide synthesis. The limiting step in the oxidative PPP, the G-6-PD reaction, can be bypassed with ribose. This leads to an elevation of the cardiac PRPP pool. The decline in ATP that is induced in many pathophysiological conditions was attenuated or even entirely prevented by i.v. infusion of ribose. In two in vivo rat models, the overloaded and catecholamine-stimulated heart and the infarcted heart, the normalization of the cardiac adenine nucleotide pool by ribose was accompanied by an improvement of global heart function. Combination of ribose with adenine or inosine in isoproterenol-treated rats was more effective to restore completely the cardiac ATP level within a short period of time than either intervention alone. (Mol Cell Biochem 160/161: 101–109, 1996)     

Effects of cadmium and zinc ions on purified lamb kidney cortex glucose-6-phosphate dehydrogenase activity

Glucose-6-phosphate dehydrogenase (G-6-PD) is the first enzyme in the pentose phosphate pathway. Cadmium is a toxic heavy metal that inhibits several enzymes. Zinc is an essential metal but overdoses of zinc have toxic effects on enzyme activities. In this study G-6-PD from lamb kidney cortex was competitively inhibited by zinc both with respect to glucose-6-phosphate (G-6-P) and NADP⁺ with Ki values of 1.066 ± 0.106 and 0.111 ± 0.007 mM respectively whereas cadmium was a non-competitive inhibitor with respect to both G-6-P and NADP⁺ Ki values of 2.028 ± 0.175 and 2.044 ± 0.289 mM respectively.     

Biochemical and genetic characterization of the lowell variant. A new phenotype of 6-phosphogluconate dehydrogenase

Summary A new electrophoretic variant of 6-phosphogluconate dehydrogenase (6PGD) has been detected in the Caucasian population in North Carolina, and family studies have shown this variant to be transmissible. This variant has been given the trivial name Lowell and the allele controlling its synthesis in conjunction with 6PGD ^A has been named 6PGD ^L . The banding pattern produced by the Lowell variant after electrophoresis is not affected by either NADP or 2-mercaptoethanol. Inhibition studies with urea and iodoacetate have shown that this variant is inhibited to approximately the same degree as the Richmond and Friendship variants. Thermostability studies have shown that the isozyme bands encoded by 6PGD ^A , 6PGD ^Elcho , 6PGD ^C , and 6PGD ^L have a relative thermal stability in the order 6PGD ^A >6PGD ^Elcho >6PGD ^C >6PGD ^L .     

全自动直接定量法与定量比值法检测红细胞葡糖-6-磷酸脱氢酶活性的比较

目的:与定量比值法比较,探讨全自动直接定量法检测红细胞葡糖-6-磷酸脱氢酶(G-6-PD)活性的可行性。方法:同时采用定量比值法(即硝基四氮唑蓝定量法)和全自动直接定量法,检测219例肝素抗凝静脉血标本的红细胞G-6-PD活性。结果:定量比值法检测G-6-PD缺乏的阳性率为9.13%,全自动直接定量法检测的G-6-PD缺乏阳性率为9.58%,两种方法检测结果无显著性差异(P>0.05)。结论:定量比值法简单易行,适用于卫生条件有限的基层医疗单位;全自动直接定量法快速准确,是一种可批量检测的理想筛选方法。     

Activity of some glycolytic and pentose phosphate pathway enzymes during the development of adventitious roots

Activities of phosphofructokinase (PFK, EC 2.7.1.11), glyceraldehyde 3-phosphate (NAD) dehydrogenase [G-3-PD(NAD), EC 1.2.1.12], glucose 6-phosphate dehydrogenase (G-6-PD, EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (6-PGD, EC 1.1.1.44) were determined in bean cuttings (Phaseolus vulgaris L. cv. Top Crop) over 4 days, encompassing adventitious root primordium initiation and development. Effects of applied auxin and “endogenous root-forming stimulus”(ERS) on enzyme activities, concentrations of reducing sugars, and primordium development were also determined during the first 4 days of propagation. Effects of auxin were determined through use of applied indole-3-acetic acid (IAA) or 2,3,5-triiodobenzoic acid. Effects of ERS were evaluated by means of decapitation of cuttings. Increased basipetal transport and increased metabolism of reducing sugars occurred in leafy cuttings in response to applied IAA and to ERS. Primordium development and activities of the four enzymes increased in leafy cuttings under conditions that simultaneously increased basipetal transport and metabolism of reducing sugars. Three types of enzyme activity response were found: (i) activity increased over time by ERS and by applied IAA [G-3-PD(NAD)], (ii) activity increased over time by ERS but not by applied IAA (PFK, G-6-PD), (iii) activity increased over time but not by ERS or applied IAA (6-PGD). Increases in G-3-PD(NAD), G-6-PD, and PFK activity in leafy cuttings were positively related to primordium development. 6-PGD activity increased in leafy cuttings during primordium development and may have supported it. However, equal increases occurred in decapitated cuttings, in which the long-term development of primordia was supressed. Results for G-3-PD(NAD) that were obtained in an experiment with jack pine (Pinus banksiana Lamb.) seedling cuttings were similar to results for the same enzyme in bean cuttings. G-3-PD(NAD) activity in naphthaleneacetic acid-treated jack pine cuttings increased with time, in comparison with untreated cuttings, before root emergence.     

Glucose-6-phosphate dehydrogenase isoenzymes in root growth zones ofVicia faba

The specific activity of glucose-6-phosphate dehydrogenase (G-6-PD) in growth zones ofVicia faba roots is increasing with cell maturation and differentiation. Changes in the total activity of G-6-PD are not associated with a change in the number of G-6-PD isoenzymes. Five G-6-PD isoenzymes were found in all root growth zones. Some differences were found in the activity of individual isoenzymes.     

Studies of enzymes connected with erythrocyte glutathione metabolism in a rural tropical population

Summary The activities of the erythrocyte enzymes hexokinase (HK), glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione peroxidase (GSH-PO) were determined in a group of 12 Europeans and in a group of 103 male Thai subjects in northern Thailand. In the Thai group there were 16 subjects with G-6-PD deficiency and 28 subjects with abnormally low levels of GR activity. A comparison of the enzyme activities in the different subgroups indicated that HK and 6-PGD are not influenced by G-6-PD deficiency whereas GR and GSH-PO activities are significantly higher in G-6-PD deficient subjects. In the group with low GR activity G-6-PD and GSH-PO showed a tendency to an elevation of activity when compared with the normal control group. Significant positive correlations exist between G-6-PD and 6-PGD in the normal group and between GR and GSH-PO in the G-6-PD deficient group. A negative correlation between GR and GSH-PO was present in the group with low GR activities. A study of the families of subjects with low activity of GR did not yield evidence for the existence of a deficiency polymorphism.

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Zusammenfassung Bei 12 Europäern und einer Gruppe von 103 männlichen thailändischen Versuchspersonen wurden die Aktivitäten der Erythrocytenenzyme Hexokinase (HK), Glucose-6-Phosphat-Dehydrogenase (G-6-PD), 6-Phosphogluconat-Dehydrogenase (6-PGD), Glutathion-Reduktase (GR) und Glutathion-Peroxidase (GSH-PO) bestimmt. In der Thai-Gruppe waren 16 Personen mit G-6-PD-Mangel und 28 Personen mit abnormal niedrigen Aktivitäten der GR. Ein Vergleich der Enzymaktivitäten in verschiedenen Untergruppen zeigte, daß HK und 6-PGD durch G-6-PD-Mangel nicht beeinflußt werden. Im Gegensatz hierzu sind die Aktivitäten der GR und der GSH-PO bei G-6-PD-Mangel signifikant erhöht. In der Gruppe mit erniedrigter GR-Aktivität bestand eine Tendenz zu erhöhten Werten für G-6-PD und GSH-PO. Die Korrelationen zwischen G-6-PD und 6-PGD in der Gruppe mit normaler G-6-PD und die zwischen GR und GSH-PO in der Gruppe mit G-6-PD-Mangel waren signifikant. In der Gruppe mit erniedrigter GR-Aktivität fand sich eine negative Korrelation zwischen GR und GSH-PO. Die Untersuchungen in Familien von Personen mit niedriger GR-Aktivität ergaben keinen sicheren Hinweis auf das Vorliegen eines GR-Mangel-Polymorphismus in der untersuchten Bevölkerung.

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Established and supported by Stiftung Volkswagenwerk, Hannover.     

Glutathione reductase deficiency in association with sickle cell and thalassaemia genes in Saudi populations

Glutathione reductase (GR) deficiency is reported to occur with a variable frequency in some populations of the world. In this study, the populations of two regions of Saudi Arabia which have a high frequency of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, were screened for GR deficiency. Studies were also carried out to investigate the frequency of GR deficiency with other genetic blood disorders. The frequencies of complete GR deficiency were 0.0065 and 0.006, while those of partial deficiency were 0.146 and 0.074 in Al-Hafouf and Khaiber, respectively. GR deficiency was encountered in combination with the sickle gene, the G-6-PD deficiency gene and the thalassaemia gene in both regions. Individuals with GR deficiency showed slightly reduced haematological parameters. In thalassaemic/GR-deficient subjects, mean cell volume and mean cell haemoglobin were low, while in sickle cell anaemia patients with GR deficiency the haematological parameters were higher than in sickle cell anaemia patients without GR deficiency.     

Adenosine deaminase polymorphism in sardinia

Summary Red blood cell adenosine deaminase and G-6-PD polymorphisms have been studied in the populations of 17 Sardinian villages located at various altitudes. A total of 1615 individuals of both sexes, with age between 7 and 14 years were examined.The negative relationship between Gd^Med gene frequency and altitude was confirmed.Adenosine deaminase polymorphism showed a considerable variability among the villages examined: ADA² frequency ranged from 0.025 to 0.106. The ADA² frequency was negatively related (p< 0.05) with Gd^Med gene frequency.

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Zusammenfassung Die Erythrocyten-Adenosin-Desaminase und Glucose-6-Phosphat-Dehydrogenase-Polymorphismen sind in Stichproben aus der Bevölkerung von 17 Dörfern auf Sardinien untersucht worden. Diese sind in verschiedener Höhe über dem Meer im zentralen Teil der Insel gelegen.Die negative Häufigkeitsbeziehung zwischen der Genfrequenz Gd^Med und der Höhenlage der Dörfer konnte bestätigt werden.Der Adenosin-Desaminase-Polymorphismus zeigt eine beträchtliche Variabilität zwischen den verschiedenen Dorfpopulationen. Die ADA²-Frequenz liegt zwischen 0,025 und 0,106. Die ADA²-Frequenz steht in negativer Beziehung (p< 0,05) zur Gd^Med-Frequenz.

     

Genetic polymorphism of glycerol-3-phosphate dehydrogenase (E.C.: 1.1.1.8)

Summary By means of starchgel electrophoresis several distinct proteins with G-3-PD activity can be detected in Primates. The relative activities of these isoenzymes are found to vary markedly from tissue to tissue. It is presumed that the G-3-PD proteins are dimers composed of two nonidentical polypeptide subunits (chain A and B), which are determined by two separate gene loci (G-3-PD _A and G-3-PD _B). In liver, kidney and skeletal muscle the subunit B is in great excess, while in heart and brain both subunits A and B are present in almost equal proportions. It is concluded, that the various isozyme patterns are the consequence of random combinations of different polypeptide chains. The results obtained so far indicate, that in Primates 2 alleles occur at the G-3-PD _A locus and 5 alleles at the G-3-PD _B locus. Formal notations are given, and a study on population genetics is reported.

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Zusammenfassung Bei den Primaten können mit der Stärkegelelektrophorese verschiedene G-3-PD-aktive Proteine nachgewiesen werden. Die transspezifische Variabilität ist beträchtlich. Für eine formalgenetische Interpretation ist das Modell zu unterlegen: zwie Cistrons G-3-PD _A und G-3-PD _B mit Information für G-3-PD-Polypeptidketten. Homozygote Individuen besitzen 3 Isoenzymbanden, da die beiden Polypeptidketten zu Dimermolekülen frei assoziieren. Heterozygote Individuen für das Cistron G-3-PD _A bzw. G-3-PD _B besitzen jeweils 6 Isoenzymbanden. Bei doppelt heterozygoten Individuen (sowohl für das Cistron G-3-PD _A als auch für G-3-PD _B) sind insgesamt 10 Isoenzymbanden zu erwarten. Unterschiede in den Syntheseraten für A- und B-Polypeptidketten bedingen eine stark ausgeprägte organspezifische Variabilität. In Leber, Niere und skeletmuskel überwiegt die Synthese für B-Ketten, im Herzmuskel und Gehirn werden A- und B-Ketten in annähernd gleicher Menge gebildet. Auf Grund der bisher vorliegenden Ergebnisse ist bei den Primaten mit 2 allelischen Varianten für das Cistron G-3-PD _A und mit 5 allelischen Varianten für das Cistron G-3-PD _B zu rechnen.

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(Director: Prof. Dr. Dr. H. Ritter)

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Supported by the Deutsche Forschungsgemeinschaft.     

Power of assaying inbreeding through sampling of phenotypes and mating types

Summary Several enzyme polymorphisms and hemoglobin variants were typed in a sample of n=219 non-related Greek blood-donors. The following gene frequencies were observed: p^a=0.201, p^b=0.701, p^c=0.098; PGD^A=0.985, PGD^c=0.015; AK¹=0.942, AK²=0.058; Hb^A=0.988, Hb^S=0.012. No polymorphic variation was seen in LDH, s-MDH, PHI, or SOD. The population genetical aspects of these results are discussed.

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Zusammenfassung An einer Stichprobe von n=219 erwachsenen griechischen Blutspendern wurden verschiedene Enzympolymorphismen und Hämoglobinvarianten untersucht. Folgende Genfrequenzen konnten beobachtet werden: p^a=0,201, p^b=0,701, p^c=0,098; PGD^A=0,985, PGD^c=0,015; AK¹=0,0942, AK²=0,058; Hb^A=0,988, Hb^S=0,012. Keine polymorphe Variation wurde bei LDH, s-MDH, PHI und SOD gefunden. Die populationsgenetischen Aspekte dieser Befunde werden diskutiert.

     

Histochemical detection of steroid synthesizing cells in the testes of goldfish,Carassius auratus,during the annual reproductive cycle

We investigated the sites of Δ⁵-3β-hydroxysteroid dehydrogenase (3 β-HSD) and glucose-6-phosphate dehydrogenase (G-6-PD) synthesis in the testes of goldfish, Carassius auratus, during the annual reproductive cycle. The histochemistry of fish gonads has been investigated previously in many species other than goldfish. The reproductive cycle of goldfish, is divided into five stages and the steroid synthesizing cells of the testes were studied during these stages, using histochemical techniques. We found that interstitial cells and seminiferous tubules are the main steroid synthesizing sites in testes of goldfish, and that enzyme activity was more intense in the interstitial cells than in the seminiferous tubules. During the pre-spawning months, 3 β-HSD and G-6-PD activities were weak compared to the spawning months.     

Genetic studies on free-ranging macaques of Cay Santiago. II. 6-phosphogluconate dehydrogenase and NADH-methemoglobin reductase (NADH-diaphorase).

For the population of 395 semi-free-ranging rhesus macaques (Macaca mulatta) that inhabited Cayo Santiago in 1976, 6-phosphogluconate dehydrogenase phenotypes of 378 animals were determined. Three phenotypes, controlled by two autosomal codominant alleles,PGD^A andPGD^B, were found by electrophoretic methods. The frequencies of the alleles are 0.898 and 0.102, respectively. The population, composed of five troops and peripheral males, is in Hardy-Weinberg equilibrium at this locus. The allele frequencies at the 6-phosphogluconate dehydrogenase locus in the population in 1976 were compared with frequencies in 1973; a statistically significant difference was found in one troop. The phenotypes of NADH-methemoglobin reductase (NADH-diaphorase) were determined electrophoretically for 372 animals. These phenotypes are probably the products of two autosomal codominant alleles,Dia¹ andDia², with frequencies of 0.786 and 0.214, respectively. The population is in equilibrium at this locus also. Tests of homogeneity at the dehydrogenase and reductase loci indicate that the allele frequencies are significantly different among the five troops in the population. Observed and expected phenotypic ratios in progeny were compared at the dehydrogenase and the reductase loci. The only significant deviation from expectation occurs among offspring of mothers heterozygous at the reductase locus. The observed distributions of alleles at the 6-phosphogluconate dehydrogenase locus and the NADH-methemoglobin reductase locus are probably the results of stochastic processes.