Biomedical subjects

G Burger

Publications and source records attributed to G Burger.

At least 37 records · Page 2Linked to original sources

PubMed1999

The complete mitochondrial DNA sequences of Nephroselmis olivacea and Pedinomonas minor. Two radically different evolutionary patterns within green algae.

Green plants appear to comprise two sister lineages, Chlorophyta (classes Chlorophyceae, Ulvophyceae, Trebouxiophyceae, and Prasinophyceae) and Streptophyta (Charophyceae and Embryophyta, or land plants). To gain insight into the nature of the ancestral green plant mitochondrial genome, we have sequenced the mitochondrial DNAs (mtDNAs) of Nephroselmis olivacea and Pedinomonas minor. These two green algae are presumptive members of the Prasinophyceae. This class is thought to include descendants of the earliest diverging green algae. We find that Nephroselmis and Pedinomonas mtDNAs differ markedly in size, gene content, and gene organization. Of the green algal mtDNAs sequenced so far, that of Nephroselmis (45,223 bp) is the most ancestral (minimally diverged) and occupies the phylogenetically most basal position within the Chlorophyta. Its repertoire of 69 genes closely resembles that in the mtDNA of Prototheca wickerhamii, a later diverging trebouxiophycean green alga. Three of the Nephroselmis genes (nad10, rpl14, and rnpB) have not been identified in previously sequenced mtDNAs of green algae and land plants. In contrast, the 25,137-bp Pedinomonas mtDNA contains only 22 genes and retains few recognizably ancestral features. In several respects, including gene content and rate of sequence divergence, Pedinomonas mtDNA resembles the reduced mtDNAs of chlamydomonad algae, with which it is robustly affiliated in phylogenetic analyses. Our results confirm the existence of two radically different patterns of mitochondrial genome evolution within the green algae.

Animals↗

PubMed1999

Mitochondrial genome evolution and the origin of eukaryotes.

Recent results from ancestral (minimally derived) protists testify to the tremendous diversity of the mitochondrial genome in various eukaryotic lineages, but also reinforce the view that mitochondria, descendants of an endosymbiotic alpha-Proteobacterium, arose only once in evolution. The serial endosymbiosis theory, currently the most popular hypothesis to explain the origin of mitochondria, postulates the capture of an alpha-proteobacterial endosymbiont by a nucleus-containing eukaryotic host resembling extant amitochondriate protists. New sequence data have challenged this scenario, instead raising the possibility that the origin of the mitochondrion was coincident with, and contributed substantially to, the origin of the nuclear genome of the eukaryotic cell. Defining more precisely the alpha-proteobacterial ancestry of the mitochondrial genome, and the contribution of the endosymbiotic event to the nuclear genome, will be essential for a full understanding of the origin and evolution of the eukaryotic cell as a whole.

Animals↗

PubMed1998

Genome structure and gene content in protist mitochondrial DNAs.

Although the collection of completely sequenced mitochondrial genomes is expanding rapidly, only recently has a phylogenetically broad representation of mtDNA sequences from protists (mostly unicellular eukaryotes) become available. This review surveys the 23 complete protist mtDNA sequences that have been determined to date, commenting on such aspects as mitochondrial genome structure, gene content, ribosomal RNA, introns, transfer RNAs and the genetic code and phylogenetic implications. We also illustrate the utility of a comparative genomics approach to gene identification by providing evidence that orfB in plant and protist mtDNAs is the homolog of atp8 , the gene in animal and fungal mtDNA that encodes subunit 8 of the F0portion of mitochondrial ATP synthase. Although several protist mtDNAs, like those of animals and most fungi, are seen to be highly derived, others appear to be have retained a number of features of the ancestral, proto-mitochondrial genome. Some of these ancestral features are also shared with plant mtDNA, although the latter have evidently expanded considerably in size, if not in gene content, in the course of evolution. Comparative analysis of protist mtDNAs is providing a new perspective on mtDNA evolution: how the original mitochondrial genome was organized, what genes it contained, and in what ways it must have changed in different eukaryotic phyla.

Amino Acid Sequence↗

PubMed1998

The Organelle Genome Database Project (GOBASE).

The taxonomically broad organelle genome database (GOBASE) organizes and integrates diverse data related to organelles (mitochondria and chloroplasts). The current version of GOBASE focuses on the mitochondrial subset of data and contains molecular sequences, RNA secondary structures and genetic maps, as well as taxonomic information for all eukaryotic species represented. The database has been designed so that complex biological queries, especially ones posed in a comparative genomics context, are supported. GOBASE has been implemented as a relational database with a web-based user interface (http://megasun.bch.umontreal.ca/gobase/gobas e.html ). Custom software tools have been written in house to assist in the population of the database, data validation, nomenclature standardization and front-end design. The database is fully operational and publicly accessible via the World Wide Web, allowing interactive browsing, sophisticated searching and easy downloading of data.

Amino Acid Sequence↗

PubMed1997

An ancestral mitochondrial DNA resembling a eubacterial genome in miniature.

Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest known relatives are the rickettsial group of alpha-proteobacteria. Because characterized mitochondrial genomes vary markedly in structure, it has been impossible to infer from them the initial form of the proto-mitochondrial genome. This would require the identification of minimally derived mitochondrial DNAs that better reflect the ancestral state. Here we describe such a primitive mitochondrial genome, in the freshwater protozoon Reclinomonas americana. This protist displays ultrastructural characteristics that ally it with the retortamonads, a protozoan group that lacks mitochondria. R. americana mtDNA (69,034 base pairs) contains the largest collection of genes (97) so far identified in any mtDNA, including genes for 5S ribosomal RNA, the RNA component of RNase P, and at least 18 proteins not previously known to be encoded in mitochondria. Most surprising are four genes specifying a multisubunit, eubacterial-type RNA polymerase. Features of gene content together with eubacterial characteristics of genome organization and expression not found before in mitochondrial genomes indicate that R. americana mtDNA more closely resembles the ancestral proto-mitochondrial genome than any other mtDNA investigated to date.

Animals↗

PubMed1996

Genes encoding the same three subunits of respiratory complex II are present in the mitochondrial DNA of two phylogenetically distant eukaryotes.

Although mitochondrial DNA is known to encode a limited number (<20) of the polypeptide components of respiratory complexes I, III, IV, and V, genes for components of complex II [succinate dehydrogenase (ubiquinone); succinate:ubiquinone oxidoreductase, EC 1.3.5.1] are conspicuously lacking in mitochondrial genomes so far characterized. Here we show that the same three subunits of complex II are encoded in the mitochondrial DNA of two phylogenetically distant eukaryotes, Porphyra purpurea (a photosynthetic red alga) and Reclinomonas americana (a heterotrophic zooflagellate). These complex II genes, sdh2, sdh3, and sdh4, are homologs, respectively, of Escherichia coli sdhB, sdhC, and sdhD. In E. coli, sdhB encodes the iron-sulfur subunit of succinate dehydrogenase (SDH), whereas sdhC and sdhD specify, respectively, apocytochrome b558 and a hydrophobic 13-kDa polypeptide, which together anchor SDH to the inner mitochondrial membrane. Amino acid sequence similarities indicate that sdh2, sdh3, and sdh4 were originally encoded in the protomitochondrial genome and have subsequently been transferred to the nuclear genome in most eukaryotes. The data presented here are consistent with the view that mitochondria constitute a monophyletic lineage.

Amino Acid Sequence↗

PubMed1995

The mitochondrial DNA of the amoeboid protozoon, Acanthamoeba castellanii: complete sequence, gene content and genome organization.

In phylogenetic trees based on comparison of nuclear small subunit rRNA sequences, Acanthamoeba castellanii (an amoeboid protozoon) is positioned near the base of the radiation leading to the animals, fungi and plants. However, the specific affiliation of this protist with the major multicellular lineages of eukaryotes is currently uncertain. To further explore the evolutionary position of A. castellanii, we have determined the complete primary sequence of its mitochondrial genome. We find that the circular mtDNA (41,591 bp; 70.6% A+T) encodes two rRNAs (small subunit and large subunit), 16 tRNAs and 33 proteins (17 subunits of the respiratory chain and 16 ribosomal proteins). As well, this genome contains eight open reading frames (ORFs) larger than 60 codons and of undefined function. Two of these ORFs (orf124 and orf142) have homologs in other mtDNAs ("orf25" and "orfB", respectively), three are unique to A. castellanii mtDNA (orf83, orf115 and orf349), and three are intronic ORFs. Among notable features of A. castellanii mtDNA are the following: (1) Genes and ORFs are all encoded on the same strand and are tightly packed, with only 6.8% of the total sequence not having an evident coding function and intergenic spacer sequences ranging from only 1 to 616 bp (average 64 bp). Ten pairs of protein-coding genes overlap by up to 38 bp and two subunits of cytochrome oxidase (COX1 and COX2) are specified by a single continuous ORF. (2) Only three introns, all group I and each containing a free-standing ORF, are present; these are localized in the 3'-half of the large subunit rRNA gene. (3) The genome encodes fewer than the minimal number of tRNA species required to support mitochondrial protein synthesis, suggesting that additional tRNAs are imported from the cytosol into A. castellanii mitochondria. Of the 16 tRNAs specified by A. castellanii mtDNA (one with an 8-nucleotide anticodon loop), 13 have been shown or are predicted to undergo a novel form of RNA editing within the acceptor stem. (4) A modified genetic code is used in which UGA specifies tryptophan. (5) Repeated sequences and obvious small sequence motifs that might represent regulatory elements are absent. In overall size, gene content and organizational pattern, A. castellanii mtDNA most closely resembles the mtDNA of the chlorophycean alga Prototheca wickerhamii (55,326 bp; 74.2% A+T), but is quite different in these respects from the mtDNA of Chlamydomonas reinhardtii (15,758 bp; 54.8% A+T), another chlorophycean alga, as well from characterized animal and fungal mitochondrial genomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthamoeba↗

PubMed1994

Complete sequence of the mitochondrial DNA of the chlorophyte alga Prototheca wickerhamii. Gene content and genome organization.

The complete nucleotide sequence of the circular mitochondrial (mt) DNA of the chlorophyte alga Prototheca wickerhamii has been determined (55,328 base-pairs, A+T content 74.2%). The genes identified encode three subunits of the cytochome oxidase, apocytochrome b, nine subunits of the NADH dehydrogenase complex (nad1 to 7, nad4L and nad9), three ATPase subunits (atp6, atp9, atp1 (also referred to as atpA)), three ribosomal RNAs (5 S (rrn5), small subunit (srn) and large subunit (lrn) RNA), 26 tRNAs, and 13 ribosomal proteins. A total of five group I introns reside in lrn and cox1, two of which include intronic open reading frames (ORFs). Five free-standing ORFs longer than 60 codons are present. Three of these ORFs are counterparts to genes encoding proteins of unknown function in plant mitochondria (orf25 and orfB of angiosperms and orf244 of liverwort), whereas two of them are unique. Mitochondrial genes are encoded on both DNA strands in a way that suggests the existence of two transcription units, each including approximately one half of the mitochondrial genome. The two intergenic regions in which transcription is believed to initiate and terminate are about ten times longer than the other intergenic regions (1118 and 1993 nt versus 100 to 150 nt). A total of 29 recurring sequence motifs (30 to 200 nt long) have been found in intergenic regions. Nine different types of motifs are present, most of them arranged as tandem repeats. These motifs may be implicated in transcription, e.g. as signals for initiation, termination and/or processing. Phylogenetic analysis on the basis of the cox1 gene strongly suggested that P. wickerhamii and plant mitochondrial genomes are monophyletic. The finding of plant-specific mitochondrial genes such as orf25, orf244, orfB and rrn5 in P. wickerhamii mitochondria corroborates this idea.

Amino Acid Sequence↗

PubMed1994

Extrachromosomal plasmids in the plant pathogenic fungus Rhizoctonia solani.

Extrachromosomal DNA elements were found in field isolates of Rhizoctonia solani belonging to anastomosis groups (AG) 1-5. An isolate of AG-5 (Rh41) contains a 3.6-kbp plasmid (pRS188) which has a similar A+T content to mitochondrial DNA. pRS188 is linear and has knob structures at its ends, as revealed by electron microscopy. Exonuclease digestions show that the linear ends of pRS188 are protected, and remain protected even after proteinase K digestion. pRS188 does not hybridise to nuclear or mitochondrial DNAs of its host isolate (Rh41), to total DNAs of other plasmid-less AG-5 isolates, or to total DNA of plasmid-harbouring isolates belonging to different AGs. Cellular-fractionation experiments suggest that pRS188 is associated with mitochondria, but it remains undecided whether this occurs inside or outside of the organelles. The nucleotide sequence of about 60% of the plasmid has been determined, revealing no open reading frame longer than 91 amino acids, and no known gene or genetic element is detected in the sequence contigs of 300-1572 bp length. Similar studies were performed with the plasmid pRS104 present in an isolate of AG-4 (Rh36), the sequence of which exhibits essentially the same features as pRS188 except that its A+T content resembles that of nuclear DNA. Pathogenicity tests reveal that the isolates Rh41 and R36 are as virulent as the plasmid-less isolates of AG-4 and -5, indicating that the plasmids do not play any role in pathogenicity.

Base Composition↗

PubMed1994

Increased levels of soluble serum interleukin-2 receptor in extrinsic allergic alveolitis correlate with interleukin-2 receptor expression on alveolar macrophages.

In a group of 20 patients with extrinsic allergic alveolitis (10 with farmer's lung, 9 with bird-breeder's lung, and 1 with humidifier's lung), we observed increased levels of soluble serum interleukin-2 receptor (ssIL-2R) with an average of 75.2 pmol (control group average, 40.6 pmol). Analysis of bronchoalveolar lavage cells by immunocytochemistry with a CD25 antibody revealed only a slight increase to 4.2% IL-2R+ cells among alveolar lymphocytes but a pronounced rise to 21.2% IL-2R+ cells among alveolar macrophages. Furthermore, cytometry revealed a fourfold higher IL-2R expression on a per cell basis for alveolar macrophages as compared with alveolar lymphocytes. A clear-cut positive correlation (p = 0.006) was found for ssIL-2R and IL-2R+ alveolar macrophages, but only a borderline correlation was found for ssIL-2R and IL-2R+ alveolar lymphocytes (p = 0.04). The finding of a concomitant decrease of IL-2R+ alveolar macrophages and of ssIL-2R on allergen avoidance further supports the notion that alveolar macrophages may be the main source of the increased ssIL-2R in patients with extrinsic allergic alveolitis.

Adult↗

PubMed1994

The significance of anticardiolipin antibodies and anti-heart muscle antibodies for the diagnosis of postpericardiotomy syndrome.

Postpericardiotomy syndrome (PPS) is a frequent complication after cardiac surgery. In a recent study, elevated anticardiolipin antibody (ACLA) titres were observed in patients with PPS. The value of anti-heart muscle antibodies (AHA) for the diagnosis of PPS remains controversial. Therefore, a prospective double-blind study was performed to test the sensitivity and specificity of ACLA and AHA for the diagnosis of PPS. ACLA titres (ELISA) and AHA, elevated by immunofluorescence, the clinical course and routine laboratory parameters were assessed in 57 patients before and after elective cardiac surgery. ACLA increased and AHA first appeared after surgery in patients both with and without PPS. The sensitivities of a > or = 1.5-fold increase in IgM-ACLA titres, of a > or = 2-fold increase in IgG-ACLA titres and of the occurrence of AHA > or = 2+ for the diagnosis of PPS were 60%, 20% and 20%. The respective specificities were 43%, 79% and 85%. Thus, after cardiac surgery, increased ACLA titres and the occurrence of AHA, as assessed by immunofluorescence, may only contribute to the diagnosis of PPS to a limited extent.

Aged↗

PubMed1994

Interlaboratory comparison of DNA image analysis. Management group report of internal quality assurance programme in the CAAC breast cancer project.

The Clinically Applied Analytical Cytometry (CAAC) project was a concerted action project in a working group measuring DNA in breast cancer. An internal quality assurance programme was established on a voluntary basis to determine the level of concordance of DNA measurements between participating laboratories. Three rounds were achieved within the time scale of the project. For each round three slides (2 prepared with Feulgen, one unstained for "in house" preparation) bearing a population of human liver cells were sent to participating laboratories. The institutions were asked to measure 200 diploid, 100 tetraploid and 50 octaploid cells by means of the image cytometry system present in the laboratory. In the third round tumor cells were added. The features integrated optical density (IOD) and AREA were reported. In the three rounds the number of participating laboratories was 11, 14 and 11, respectively. The interlaboratory variation expressed as the CV of IOD for the three rounds ranged from 2-18%. Calculation of the 4c/2c and 8c/2c ratios revealed a high precision for most of the instruments. Comparison of measurements in specimens stained in the participating and central laboratory showed similar CV values. Measuring 200 nuclei in image analysis is too low a number to obtain a reliable estimate of the S-phase fraction. In conclusion, the interlaboratory intercomparison of DNA measurements performed on different instruments is well feasible and could facilitate improvement in quality standards.

Analysis of Variance↗

PubMed1994

Problems concerning the quality of DNA measurements on Feulgen-stained imprints. A study of five fixation techniques.

Feulgen-stained rat liver imprints were investigated, and hepatocytes, lymphocytes and granulocytes were measured. Additionally, chicken erythrocytes placed on the slides were measured as an external DNA standard. The imprints were treated according to five different fixation protocols. The measured integrated optical density (IOD) was normalized according to the leukocytes and afterwards scaled according to the diploid hepatocytes. The mean IOD, coefficient of variation (CV), standard error of the mean (SEM) and IOD ratios of distinct cell groups were calculated. The CV of the IOD for hepatocytes was slightly better for air-dried preparations. It was larger for leukocytes than for hepatocytes and worst for chicken erythrocytes. The SEM of hepatocytes did not show remarkable differences between the fixation groups; in general it was near 1%. In all cases the IOD ratios of 2c, 4c and 8c hepatocytes reasonably well followed the expected ratio of 1:2:4 except for wet, formalin-fixed hepatocytes (3.8). The ratios of leukocytes to 2c hepatocytes were about 1.0 for air-dried preparations but considerably lower (0.85) for wet fixation in formalin. The IOD ratios of chicken erythrocytes to 2C hepatocytes varied from 0.33 to 0.35. The deviation of the ratios of single specimens from the estimated mean of a fixation group are described.

Animals↗

PubMed1994

Malignancy associated changes in squamous epithelium of the head and neck region.

Subtle cellular changes are known to exist in normal host tissue adjacent to tumours. These are called malignancy associated changes (MAC). To get more insight into the degree of expression and local spread of such changes we performed high resolution image cytometry on visually normal intermediate cell nuclei in smears from patients with laryngeal or pharyngeal squamous cancer. The smears were taken from the tumour surface, from a border region of the tumour and from a distant unsuspicious buccal site. In addition buccal smears from healthy control persons were examined. In a pilot study smears from 12 cancer patients and 11 control persons and in a succeeding validation study 63 controls, 18 non-tumour patients and 25 cancer patients were investigated. In both studies the occurrence of MACs was demonstrated quantitatively. In cancer patients normal appearing intermediate cells from the three different sampling sites could be discriminated with 65% in the pilot study and with 53% correct classification in the validation study. In addition the influences of smoking behaviour and sex were investigated in the control group. Only in the latter case there was a significant difference between female and male with a 63% correct cell and 71% correct specimen classification.

Carcinoma, Squamous Cell↗

PubMed1994

High resolution image-cytometric differentiation of hormone sensitive and hormone insensitive prostatic carcinomas.

Until the present it was not possible to predict hormone sensitivity of prostatic carcinoma. Based on studies correlating image cytometric results of hormone receptor negative and hormone receptor positive breast carcinomas, the present study aims at separating responders and non-responders to hormone therapy in metastatic prostatic carcinoma. From May-Grünwald-Giemsa stained slides of fine needle aspirates of 23 patients with metastasizing prostatic carcinoma about 100 nuclei per slide were taken by TV camera for image-cytometric processing. One thousand and twenty-two nuclei came from 10 patients who showed tumour regression for at least 36 months and who all survived for more than 5 years. One thousand three hundred and thirty-two nuclei were from prostatic aspirates of patients who showed a continuous tumour progression despite receiving hormone therapy. All patients of the latter group died within 5 years. A correct classification of the patient groups of responders and non-responders was possible in 19-21 of 23 cases by means of high resolution image analysis including nuclear structural features. It was found that even simple planimetric features, like the nuclear perimeter, or densitometric features, such as the total nuclear extinction, differed markedly between the two groups. The data show that nuclei from hormone sensitive prostatic carcinoma are distinct from those of non-sensitive ones in the present series. The interpretation of results must take into account that the very strict criteria for hormone sensitivity leads to a highly selected patient group. The application of the method to an unselected patient group can be presumed to yield a higher rate of false classifications.

Azure Stains↗

PubMed1994

Biological monitoring of chemical exposure in nickel workers by imaging cytometry (ICM) of nasal smears.

Highly sensitive and inexpensive methods that are not time consuming are desirable for monitoring the workplace environment for the detection of cytotoxic hazards, particularly cancerous risks. It is possible to detect precancerous and cancerous lesions in samples taken by brushing the nose, but the cytological diagnoses can be affected by an inability to obtain representative smears from the sometimes very small focal lesions, and uncertainties in the subjective interpretation of suspicious cells when these are small in number. In an attempt to improve diagnosis we applied imaging cytometry (ICM) and tested the concept of malignancy-associated changes (MAC) in routinely Papanicolaou-stained smears. Cells of non-goblet type that visually appeared normal were selected from nickel workers with and without dysplastic lesions of the nasal mucosa. A set of nuclear features was measured by ICM and used for discriminant analysis. We were able to differentiate between workers with non-dysplastic normal and suspicious mucosa smears and those with dysplastic lesions. Unexpectedly, it was found possible to distinguish between workers in the roasting/smelting and the electrolysis departments, who were exposed to different carcinogenic nickel compounds. A further surprising finding was the possibility to distinguish smokers and non-smokers among the nickel workers.

Adult↗

PubMed1993

Mitochondrial genes in the colourless alga Prototheca wickerhamii resemble plant genes in their exons but fungal genes in their introns.

The mitochondrial DNA from the colourless alga Prototheca wickerhamii contains two mosaic genes as was revealed from complete sequencing of the circular extranuclear genome. The genes for the large subunit of the ribosomal RNA (LSUrRNA) as well as for subunit I of the cytochrome oxidase (coxI) carry two and three intronic sequences respectively. On the basis of their canonical nucleotide sequences they can be classified as group I introns. Phylogenetic comparisons of the coxI protein sequences allow us to conclude that the P.wickerhamii mtDNA is much closer related to higher plant mtDNAs than to those of the chlorophyte alga C.reinhardtii. The comparison of the intron sequences revealed several unusual features: (1) The P.wickerhamii introns are structurally related to mitochondrial introns from various ascomycetous fungi. (2) Phylogenetic analyses indicate a close relationship between fungal and algal intronic sequences. (3) The P. wickerhamii introns are located at positions within the structural genes which can be considered as preferred intron insertion sites in homologous mitochondrial genes from fungi or liverwort. In all cases, the sequences adjacent to the insertion sites are very well conserved over large evolutionary distances. Our finding of highly similar introns in fungi and algae is consistent with the idea that introns have already been present in the bacterial ancestors of present day mitochondria and evolved concomitantly with the organelles.

Amino Acid Sequence↗

PubMed1993

Concomitant modulation of serum-soluble interleukin-2 receptor and alveolar macrophage interleukin-2 receptor in sarcoidosis.

Interleukin-2 receptor (IL-2R) expression on bronchoalveolar lavage (BAL) cells was studied in patients with sarcoidosis using immune cytochemistry and cytometric analysis. A low percentage of alveolar lymphocytes (AL) was found positive for IL-2R, with 7% in patients with impaired lung function and 6% in patients with normal lung function (0.4% in control subjects). Expression of IL-2R on alveolar macrophages (AM) was considerably higher, with 25% in patients with lung function impairment compared with 14% in patients without lung function impairment (1.5% in control subjects). Serum-soluble IL-2R (ssIL-2R) was significantly elevated only in patients with impaired lung function (140.0 pM), but not in patients with normal lung function (52.2 pM; control subjects, 40.0 pM). These elevated levels of ssIL-2R positively correlated with the percentage of IL-2R positive AM (p < 0.001). Immunosuppressive treatment in three patients resulted in a decrease of IL-2R+ AM and in a decrease of ssIL-2R, whereas IL-2R+ AL were unaffected. The positive correlation and the concomitant decrease of IL-2R+ AM and ssIL-2R are consistent with the idea that in sarcoidosis with clinically apparent lung involvement, elevated levels of ssIL-2R may be derived from AM and may thus be a useful indicator of the degree of activation of these cells.

Adult↗