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PubMed2026

Mitotic karyotyping and FISH mapping of the gender-specific locus indicate an advanced XY system in Hippophae rhamnoides.

Hippophae rhamnoides ssp. turkestanica, a subdioecious plant inhabiting the cold desert of the Indian Himalaya, has gained immense recognition for its nutritional and medicinal values. In recent years, the plant species has proven to be a suitable system to understand the evolution of dioecy. Despite its biological significance, the cytogenetics of this dioecious plant is unclear due to various conflicting accounts of its X-Y chromosome system, particularly the length of Y-chromosome. In this study, we resolved these ambiguities through comprehensive cytogenetic analyses across diverse western Himalayan populations. Using morphometric analysis and fluorescence in situ hybridization (FISH) with a gender-specific marker (HRMSSR), we confirmed homomorphic XX chromosomes in females and heteromorphic sex-chromosomes in males with a notably smaller Y-chromosome. The investigation also revealed a predominant somatic chromosome number of 2n = 24, although minor deviations (2n = 18, 20, 22) appeared at the seed level. These findings highlight an evolutionarily advanced sex-chromosome system. This first detailed cytogenetic investigation of Himalayan Seabuckthorn provides critical insights into the chromosomal architecture, laying a crucial foundation for future evolutionary, genomic, and conservation studies in the species.

Chromosome Mapping↗
PubMed1984

[New visual area on the inferior wall of the cruciate sulcus of the cat brain].

Properties of 187 neurons were studied in the lower bank of that part of cruciate sulcus where electrical stimulation evoked conjugate unidirectional oculomotor saccades. 172 neurons responded to visual stimulation. Neurons in the superficial cortical layers responded to conventional stimuli: light and dark spots or slits stationary or moving with the speed up to 30 degrees/s. These neurons had no orientational selectivity but sometimes showed directional selectivity. In the intermediate layers maximal responses were obtained when a flittering bird was presented to the cat; no responses were observed to conventional stimulation. Main feature of many neurons in the deep layers was selectivity to the motion in the depth in some parts of the visual field. This selectivity was invariant to the direction of contrast between stimulus and background. Visual responses in all layers were seen only in the state of arousal (during desynchronization in EEG) and were absent in the state of quiet wakefulness. All studied neurons showed no responses to acoustic or somatic stimulation. Neurons in the medial wall of the brain under the cruciate sulcus did not respond to visual stimulation but responded in correlation with definite eye movements. It is suggested that in this part of the brain two retinotopically organized areas are present one of which is connected with visual function and another with eye movements.

Animals↗
PubMed1994

Structure, diversity, and evolution of the T-cell receptor VB gene repertoire in primates.

AB T-cell receptors (TCR) that recognize major histocompatibility complex (MHC)/peptide antigen complexes regulate humoral and cellular arms of the adaptive immune response. Antigen binding sites of MHC and immunoglobulin heavy chain variable regions (Igh-V) are subject to diversity enhancing selection. We sought to establish whether positive Darwinian selection has driven diversity of TCRBV chains in the primate lineage by sequencing rearranged TCR from rhesus monkeys and chimpanzees and comparing them with those of humans. Rates of synonymous (silent) and nonsynonymous (replacement) substitutions indicate selection against amino acid replacements in TCRBV frameworks, and relaxation of these constraints in putative MHC/peptide contact sites. The lack of positive selection for variability in likely ligand contact sites suggests that mechanisms generating somatic diversity in TCR junctional regions have relaxed the pressure for selection of variability in the TCR V region encoded in the germline.

Amino Acid Sequence↗
PubMed2003

Conservation of Dnmt1o cytosine methyltransferase in the marsupial Monodelphis domestica.

Imprinted genes have been identified in both eutherian mammals and in marsupials. In eutherian species, there is a conservation of the imprinting process, both in terms of the genes imprinted and the epigenetic inheritance mechanism. In the mouse, the inheritance of gametic methylation patterns depends on an oocyte-derived isoform of the Dnmt1 (cytosine-5)-methyltransferase protein, Dnmt1o, which functions during preimplantation development to maintain methylation patterns on imprinted alleles. To determine if this component of genomic imprinting is also found in marsupials, Dnmt1 isoforms were examined in somatic cells and germ cells of the South American opossum Monodelphis domestica. There is a Dnmt1o protein in Monodelphis oocytes that is synthesized, as in the mouse, from a different transcript than the somatic Dnmt1 protein. Thus, an essential component of imprinting in eutherian mammals is found in a marsupial species, suggesting that marsupials and eutherian mammals imprint their genes with the same methylation-dependent mechanism.

Amino Acid Sequence↗
PubMed2006

Alternative adaptive immunity in invertebrates.

Vertebrate adaptive immunity is characterized by challenge-specific long-term protection. This specific memory is achieved through the vast diversity of somatically rearranged immunological receptors such as antibodies. Whether or not invertebrates are capable of a comparable phenotypic plasticity and memory has long been a matter of debate. A recent study on Anopheles gambiae mosquitoes now establishes Down syndrome cell adhesion molecule (Dscam) as a key immune surveillance factor with characteristics analogous to antibodies.

Adaptation, Biological↗
PubMed1977

Human beta-glucuronidase: assignment of the structural gene to chromosome 7 using somatic cell hybrids.

beta-Glucuronidase (GUS) has become an important enzyme model for the genetic study of molecular disease, enzyme realization, and therapy, and for the biogenesis and function of the lysosome and lysosomal enzymes. The genetics of human beta-glucuronidase was investigated utilizing 188 primary man-mouse and man-chinese hamster somatic cell hybrids segregating human chromosomes. Cell hybrids were derived from 16 different fusion experiments involving cells from ten different and unrelated individuals and six different rodent cell lines. The genetic relationship of GUS to 28 enzyme markers representing 19 linkage groups was determined, and chromosome studies on selected cell hybrids were performed. The evidence indicates that the beta-glucuronidase gene is assigned to chromosome 7 in man. Comparative linkage data in man and mouse indicate that the structural gene GUS is located in a region on chromosome 7 that has remained conserved during evolution. Involvement of other chromosomes whose genes may be important in the final expression of GUS was not observed. A tetrameric structure of human beta-glucuronidase was demonstrated by the formation of three heteropolymers migrating between the human and mouse molecular forms in chromosome 7 positive cell hybrids. Linkage of GUS to other lysosomal enzyme genes was investigated. beta-Hexosaminidase (HEXB) was assigned to chromosome 5; acid phosphatase2 (ACP2) and esterase A4 (ES-A4) were assigned to chromosome 11; HEXA was not linked to GUS; and alpha-galactosidase (alpha-GAL) was localized on the X chromosome. These assignments are consistent with previous reports. Evidence was not obtained for a cluster of lysosomal enzyme structural genes. In demonstrating that GUS was not assigned to chromosome 9 utilizing an X/9 translocation segregating in cell hybrids, the gene coding for human adenylate kinase1 was confirmed to be located on chromosome 9.

Adenylate Kinase↗
PubMed1989

Specificity of the cardiac response to conspecific vocalization in chimpanzees.

Heart rate measures were used to examine the functional response of young chimpanzees and orangutans to acoustic stimuli, including white noise and chimpanzee vocalizations (threat, stress, and alarm). The initial response of the animals to all stimuli was characterized by a prominent cardiac deceleration and an increase in heart period variability. The deceleratory responses persisted with repeated presentations of the noise, stress, and alarm stimuli. In contrast, the response of chimpanzees to the conspecific threat stimulus reverted over trials to a notable cardiac acceleration. This acceleratory response was not attributable to potential patterns of evoked somatic responses. The features of the cardiac response, together with the results of frequency-domain analyses of heart period variability, suggest that this acceleratory response was consistent with the evocation of an aversive or a defensive reaction characterized by sympathetic activation. This pattern of cardiac response appeared early in ontogeny (within 48 hr postnatally) and was not manifest in orangutans. Taken together, the results suggest the existence of specialized perceptual processing mechanisms for vocal stimuli in the chimpanzee. Further examination of these mechanisms may contribute to our understanding of central perceptual processes and the evolution of vocal communication.

Age Factors↗
PubMed1990

A somatic gene rearrangement contributing to genetic diversity in maize.

We have discovered a somatic genomic rearrangement that occurs at high frequency at a duplicated zein locus in certain cultures of the maize inbred line A188. The rearranged allele arises from the duplication by a two-step process involving a homologous recombination and a second event, which may be a deletion, inversion, or insertion; both steps always occur together. The frequency of rearrangement is lower in homozygous states of the parental allele than in heterozygotes. In both cases, the rearrangement is shown to be mitotic. The rearranged product can be transmitted through meiosis, providing another mechanism for genome evolution in higher eukaryotes.

Base Sequence↗
PubMedDate not supplied

[The late results of respiratory kinesitherapy in tubercular serofibrinous pleurisy].

The authors have investigated 93 cases with sero-fibrinous pleurisy in their antecedents, and that had kinetotherapy during their disease. All the cases were controlled from the viewpoint of the respiratory function, as well as by radiological and electrocardiographic methods. Changes in the ventilatory function were evaluated by increased VEMS in absolute value in contrast with the VEMS value on hospitalization. The general late results of respiratory kinetotherapy were reflected in the fact that 84% of the cases presented either significant increase in the value of VEMS (56%), or had stationary values (28%). The most significant functional increases were noted in the patients who were under the age of 18 years upon release from hospital (median age : 14,8 years), and were mostly due to somatic development, and physical activity. The positive effects of physical activity in the frame of the occupation of the patients were amplified by respiratory kinetotherapy continued at home. Respiratory kinetotherapy demonstrated its efficiency especially in the subjects from lowage groups, and males had better results than females. Advanced age, important pleural sequels, as well as other disturbances, without apparent relation to the pleurisy, had negative effects. In the present conditions of treatment (chemotherapy + corticoid therapy and immediate and long-duration kinetotherapy) sero-fibrinous pleurisy has no significant impact on the socio-professional evolution of the patient.

Adolescent↗
PubMed1994

The evolution of cell lineage in nematodes.

The invariant development of free-living nematodes combined with the extensive knowledge of Caenorhabditis elegans developmental biology provides an experimental system for an analysis of the evolution of developmental mechanisms. We have collected a number of new nematode species from soil samples. Most are easily cultured and their development can be analyzed at the level of individual cells using techniques standard to Caenorhabditis. So far, we have focused on differences in the development of the vulva among species of the families Rhabditidae and Panagrolaimidae. Preceding vulval development, twelve Pn cells migrate into the ventral cord and divide to produce posterior daughters [Pn.p cells] whose fates vary in a position specific manner [from P1.p anterior to P12.p posterior]. In C. elegans hermaphrodites, P(3-8).p are tripotent and form an equivalence group. These cells can express either of two vulval fates (1 degree or 2 degrees) in response to a signal from the anchor cell of the somatic gonad, or a nonvulval fate (3 degrees), resulting in a 3 degrees-3 degrees-2 degrees-1 degree-2 degrees-3 degrees pattern of cell fates. Evolutionary differences in vulval development include the number of cells in the vulval equivalence group, the number of 1 degree cells, the number of progeny generated by each vulval precursor cell, and the position of VPCs before morphogenesis. Examples of three Rhabditidae genera have a posterior vulva in the position of P9-P11 ectoblasts. In Cruznema tripartitum, P(5-7).p form the vulva as in Caenorhabditis, but they migrate posteriorly before dividing. Induction occurs after the gonad grows posteriorly to the position of P(5-7).p cells. In two other species, Mesorhabditis sp. PS 1179 and Teratorhabditis palmarum, we have found changes in induction and competence with respect to their presumably more C. elegans-like ancestor. In Mesorhabditis, P(5-7).p form the vulva after migrating to a posterior position. However, the gonad is not required to specify the pattern of cell fates 3 degrees-2 degrees-1 degree-2 degrees-3 degrees. Moreover, the Pn.p cells are not equivalent in their potentials to form the vulva. A regulatory constraint in this family thus forces the same set of precursors to generate the vulva, rather than more appropriately positioned Pn.p cells.

Animals↗
PubMed2005

Variety of antimicrobial peptides in the Bombina maxima toad and evidence of their rapid diversification.

Antimicrobial peptides secreted by the skin of many amphibians play an important role in innate immunity. From two skin cDNA libraries of two individuals of the Chinese red belly toad (Bombina maxima), we identified 56 different antimicrobial peptide cDNA sequences, each of which encodes a precursor peptide that can give rise to two kinds of antimicrobial peptides, maximin and maximin H. Among these cDNA, we found that the mean number of nucleotide substitution per non-synonymous site in both the maximin and maximin H domains significantly exceed the mean number of nucleotide substitution per synonymous site, whereas the same pattern was not observed in other structural regions, such as the signal and propiece peptide regions, suggesting that these antimicrobial peptide genes have been experiencing rapid diversification driven by Darwinian selection. We cloned and sequenced seven genes amplified from skin or liver genomic DNA. These genes have three exons and share the same gene structure, in which both maximin and maximin H are encoded by the third exon. This suggests that alternative splicing and somatic recombination are less likely to play a role in creating the diversity of maximins and maximin Hs. The gene trees based on different domain regions revealed that domain shuffling or gene conversion among these genes might have happened frequently.

Amino Acid Sequence↗
PubMed1996

Separate sexes and the mitochondrial theory of ageing.

An hypothesis is presented by which gamete specialization resolves a conflict between the function and replication of mitochondria. The function of mitochondria is to synthesize ATP by oxidative phosphorylation, which is coupled to respiratory electron transport. This requires a mitochondrial genetic system. However, "incorrect" electron transfers produce free radicals that cause mutation, and the frequency of these events is increased by mutation. Mitochondrial function is therefore detrimental to the fidelity of mitochondrial replication. Damage to somatic mitochondrial DNA may accumulate within, and indeed determine, the life span of individual organisms. Motility of one gamete is required for fertilization, and requires ATP. It is proposed that male gametes maximize energy production for motility by sacrificing mitochondrial DNA to electron transfer and its mutagenic by-products, while female gametes, which are non-motile, repress mitochondrial oxidative phosphorylation, thus protecting mitochondrial DNA for faithful transmission between generations. Male gametes then make no contribution to the mitochondrial genome of the zygote: mitochondria are maternally inherited. This testable hypothesis may help to explain the evolution of separate sexes and a number of their characteristics. Maternal inheritance of chloroplasts may be explained in a similar way, and contribute to the maintenance of separate sexes in plants.

Aging↗
PubMed2003

Characterization and molecular modeling of a highly stable anti-Hepatitis B surface antigen scFv.

We raised a mouse monoclonal antibody (5S) against the 'a' epitope of the Hepatitis B surface antigen (HBsAg) by selecting for binding of the hybridoma supernatant in conditions that usually destabilize protein-protein interactions. This antibody, which was protective in an in vitro assay, had a high affinity with a relative dissociation constant in the nanomolar range. It also displayed stable binding to antigen in conditions that usually destabilize antigen-antibody interactions, like 30% DMSO, 8 M urea, 4 M NaCl, 1 M guanidium HCl and extremes of pH. The variable regions of the antibody were cloned and expressed as an single chain variable fragment (scFv) (A5). A5 had a relative affinity comparable to the mouse monoclonal and showed antigen binding in presence of 20% DMSO, 8 M urea and 3 M NaCl. It bound the antigen in the pH range of 6-8, though its tolerance for guanidium HCl was reduced. Sequence analysis demonstrated a significant increase in the frequency of somatic replacement mutations in CDRs over framework regions in the light but not in the heavy chain. A comparison of the molecular models of the variable regions of the 5S antibody and its germ-line precursor revealed that critical mutations in the heavy and light chains interface resulted in better inter-chain packing and in the movement of CDR H3 and CDR L1 from their germline positions, which may be important for better antigen binding. In addition to providing a reagent for neutralizing for the virus, such an antibody provides a model for the evolution of stable high affinity interaction during antibody maturation.

Amino Acid Sequence↗
PubMed1998

Localization and genomic organization of sheep antimicrobial peptide genes.

Antimicrobial peptides are an abundant and diverse component of animal innate immunity. Within mammalian species, defensins and cathelicidins are the two principal antimicrobial peptide families. We identified and sequenced ten new sheep genes which encode potential antimicrobial peptides including two beta-defensins and eight cathelicidins. We mapped the two-exon beta-defensin genes to sheep chromosome 26 and the four-exon cathelicidin genes to sheep chromosome 19 using sheep-hamster somatic cell hybrids in conjunction with flow-sorted sheep chromosomes. These assignments confirm homology between sheep, cattle, mouse, and human antimicrobial peptide gene families. Contig construction for the sheep cathelicidin gene family demonstrates that three genes, OaDodeA, OaDodeB, and OaMAP-34, are present head-to-tail in a 14.5 kb region, and that four proline/arginine-rich genes, OaBac5, OaBac7.5, OaBac11, and OaBac6, are arranged head-to-tail in a region covering 30.5 kb. This richly diverse family of sheep cathelicidin peptides is encoded in a gene array which may reflect the mechanism of its evolution.

Amino Acid Sequence↗
PubMed1979

Cytogenetic characteristics of 26 polyethylene glycol-induced human-hamster hybrid cell lines.

A cytological analysis of 26 polyethylene glycol (PEG) induced human/hamster hybrid lines has shown that such lines are similar to inactivated Sendai virus (ISV) induced hybrids in respect to stability, retention of specific chromosomes, and cell selection. The evolution of stable hybrid cell lines carrying variable human chromosome complements depends upon a balance being established between the retained human and hamster genomes. This balance is a result of random loss of human and hamster chromosomes followed by selection of the fittest stem lines. A major mechanism ofchromosome loss may be fragmentation and elimination of acentric fragments. Twelve of the 26 lines had stabilized by the 30th passage, an incidence similar to that found with ISV-induced hybrids studied in this laboratory. Thus, PEG may be considered to be an ideal chemical for inducing somatic cell hybrids for genetic analysis.

Animals↗
PubMed1978

Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox.

The 40,000-fold variation in eukaryote haploid DNA content is unrelated to organismic complexity or to the numbers of protein-coding genes. In eukaryote microorganisms, as well as in animals and plants, DNA content is strongly correlated with cell volume and nuclear volume, and with cell cycle length and minimum generation time. These correlations are simply explained by postulating that DNA has 2 major functions unrelated to its protein-coding capacity: (1) the control of cell volume by the number of replicon origins, and (2) the determination of nuclear volume by the overall bulk of the DNA: cell growth rates are determined by the cell volume and by the area of the nuclear envelope available for nucleocytoplasmic transport of RNA, which in turn depends on the nuclear volume and therefore on the DNA content. During evolution nuclear volume, and therefore DNA content, has to be adjusted to the cell volume to allow reasonable growth rates. The great diversity of cell volumes and growth rates, and therefore of DNA contents, among eukaryotes results from a varying balance in different species between r-selection, which favours small cells and rapid growth rates and therefore low DNA C-values, and K-selection which favours large cells and slow growth rates and therefore high DNA C-values. In multicellular organisms cell size needs to vary in different tissues: size differences between somatic cells result from polyteny, endopolyploidy, or the synthesis of nucleoskeletal RNA. Conflict between the need for large ova and small somatic cells explains why lampbrush chromosomes, nurse cells, chromatin diminution and chromosome elimination evolved. Similar evolutionary considerations clarify the nature of polygenes, the significance of the distribution of haploidy, diploidy and dikaryosis in life cycles and of double fertilization in angiosperms, and of heteroploidy despite DNA constancy in cultured cells, and other puzzles in eukaryote chromosome biology. Eukaryote DNA can be divided into genic DNA (G-DNA), which codes for proteins (or serves as recognition sites for proteins involved in transcription, replication and recombination), and nucleoskeletal DNA (S-DNA) which exists only because of its nucleoskeletal role in determining the nuclear volume (which it shares with G-DNA, and performs not only directly, but also indirectly by coding for nucleoskeletal RNA). Mechanistic and evolutionary implications of this are discussed.

Animals↗
PubMed1994

Phylogeny through brain traits: more characters for the analysis of mammalian evolution.

We have assembled data on nine brain traits, in addition to the fifteen we have previously described, which provide new evidence for assessing mammalian relationships. States of these characters are tabulated as they occur in each of 152 mammalian species, providing data in numerically ordered form, useful for multiple analyses of phylogenetic relationships in programs which take into account variations in several different characters simultaneously. Derived states of each of the nine traits are characteristic of certain restricted groups of mammals; (1) mirroring of the complete SI body representation in isocortex (anthropoid primates); (2) loss of the accessory olfactory bulbs (sirenians, cetaceans, most bats, catarrhine primates); (3) Rindenkerne, clumps of cell bodies in layer 6 of cerebral cortex (sirenians); (4) posteriorly-pointing digits in the SI body representation (bats, both mega- and micro-); (5) equivalent tectopetal connections to the anterior colliculus of one side from both retinas, rather than predominantly from the contralateral retina (primates and megabats); (6) loss of lamination in dorsal cochlear nuclei (anthropoid primates, bats, seals, sirenians, cetaceans); (7) separation of claustrum from cerebral cortex (diprotodont marsupials, carnivores, artiodactyls, perissodactyls, hyracoids, cetaceans and primates), (8) presence of a complete secondary (SII) somatic sensory region of cerebral cortex (therians-all extant mammals other than monotremes), and (9) presence of a distinct external cuneate nucleus among the nuclei of the dorsal columns (all mammalian groups except monotremes and sirenians). Two examples of phylogenetic trees derived from these data are presented. These sample trees maintain the segregation of the monotremes and the marsupials, and the basic dichotomy of placentals seen in our earlier trees based entirely on brain data. They also show: an orderly sequence of bifurcations (rather than the commonly seen multifurcation near the base of the radiation) in the reconstruction of placental relationships; extremes of derivation for the Cetacea, the Chiroptera, and the Sirenia (in concordance with trees based on other data); a ferungulate association of Carnivora, Perissodactyla, Artiodactyla, Hyracoidea and Sirenia; and an assemblage of related Dermoptera, Primates, Scandentia, and Chiroptera which in this model also includes Insectivora and Macroscelidea. Analyses based on brain characters can reinforce conclusions based on other data, while at the same time introducing new ideas about relationships. Neural traits provide a source of data independent of those commonly used in phylogenetic analysis, and are extremely valuable for testing old hypotheses and for introducing new ones.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Aging is a deprivation syndrome driven by a germ-soma conflict.

Evolution through natural selection can be described as driven by a perpetual conflict of individuals competing for limited resources. Recently, I postulated that the shortage of resources godfathered the evolutionary achievements of the differentiation-apoptosis programming [Rev. Neurosci. 12 (2001) 217]. Unicellular deprivation-induced differentiation into germ cell-like spores can be regarded as the archaic reproduction events which were fueled by the remains of the fratricided cells of the apoptotic fruiting body. Evidence has been accumulated suggesting that conserved through the ages as the evolutionary legacy of the germ-soma conflict, the somatic loss of immortality during the ontogenetic segregation of primordial germ cells recapitulates the archaic fate of the fruiting body. In this heritage, somatic death is a germ cell-triggered event and has been established as evolutionary-fixed default state following asymmetric reproduction in a world of finite resources. Aging, on the other hand, is the stress resistance-dependent phenotype of the somatic resilience that counteracts the germ cell-inflicted death pathway. Thus, aging is a survival response and, in contrast to current beliefs, is antagonistically linked to death that is not imposed by group selection but enforced upon the soma by the selfish genes of the "enemy within". Environmental conditions shape the trade-off solutions as compromise between the conflicting germ-soma interests. Mechanistically, the neuroendocrine system, particularly those components that control energy balance, reproduction and stress responses, orchestrate these events. The reproductive phase is a self-limited process that moulds onset and progress of senescence with germ cell-dependent factors, e.g. gonadal hormones. These degenerate the regulatory pacemakers of the pineal-hypothalamic-pituitary network and its peripheral, e.g. thymic, gonadal and adrenal targets thereby eroding the trophic milieu. The ensuing cellular metabolic stress engenders adaptive adjustments of the glucose-fatty acid cycle, responses that are adequate and thus fitness-boosting under fuel shortage (e.g. during caloric restriction) but become detrimental under fuel abundance. In a Janus-faced capacity, the cellular stress response apparatus expresses both tolerogenic and mutagenic features of the social and asocial deprivation responses [Rev. Neurosci. 12 (2001) 217]. Mediated by the derangement of the energy-Ca(2+)-redox homeostatic triangle, a mosaic of dedifferentiation/apoptosis and mutagenic responses actuates the gradual exhaustion of functional reserves and eventually results in a multitude of aging-related diseases. This scenario reconciles programmed and stochastic features of aging and resolves the major inconsistencies of current theories by linking ultimate and proximate causes of aging. Reproduction, differentiation, apoptosis, stress response and metabolism are merged into a coherent regulatory network that stages aging as a naturally selected, germ cell-triggered and reproductive phase-modulated deprivation response.

Aging↗