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Diversification in the concept of "birth and death": the controversy about "brain death and organ transplantation" in Japan.

There is a lot of hesitation in Japan in defining brain death as the death of the individual and in proceeding to organ transplantation. Regarding the diagnostic criteria of brain death, those issued by the Japanese Ministry of Health and Welfare in 1985 are sufficient for judgment of brain death. Many people, however, do not accept brain death as death of the individual, and even those who admit brain death as death of the individual hesitate to approve of the actual removal of organs from brain dead patients. Thus, the controversy about brain death in Japan appears to be separated from the objective of organ transplantation.

Brain Death↗

Cell diversification within the myogenic lineage: in vitro generation of two types of myoblasts from a single myogenic progenitor cell.

We show that a single myogenic progenitor cell in vitro generates two types of myoblasts committed to two distinct myogenic cell lineages. Using fast and slow myosin heavy chain isoform content to define myotube type, we found that myogenic cells from fetal quail (day 10 in ovo) formed two types of myotubes in vitro: fast and mixed fast/slow. Clonal analysis showed that these two types of myotubes were formed from two types of myoblasts committed to distinct fast and fast/slow lineages. Serial subcloning demonstrated that the initial myoblast progeny of an individual myogenic progenitor cell were in the fast lineage, whereas later progeny were in the fast/slow lineage. Fast and slow myosin expression within particular myotubes reflects the genetic processes underlying myoblast commitment to diverse myogenic lineages.

Animals↗

Light-chain diversification during pre-B cell differentiation.

The possibility that a committed normal pre-B cell can generate progeny expressing more than one light chain was studied by isoelectric focusing of supernatants from pre-B cells cultured at limiting dilution. Supernatants from mitogen-stimulated mature spleen B-cells analysed on day 6 have shown the presence of a rather homogeneous IgM spectrotype profile. Supernatants from the 8-10-day cultures were usually negative. Isoelectric focusing profiles of supernatants from cultures of bone marrow pre-B cells were different from those of mature spleen cells. Many IgM spectrotypes appeared in the culture supernatants of bone marrow pre-B cells between days 6 and 13, whether the cultures were negative or restricted in their IgM profiles on day 6. These results support the idea that normal pre-B cells, during differentiation, can associate a variety of light chains with an already chosen mu heavy chain.

Animals↗

Junctional diversification in the generation of the precursor of a discrete immune response.

Phosphocholine (PC)-specific antibodies that arise in the mouse in response to Proteus morganii (PM) and use V1-DFL16.1-JH1 are characterized by a number of recurring mutations. Most striking is an invariant A for G substitution in codon 95 of VH which results in an asparagine instead of aspartate at that position. Because of the apparent importance of this substitution in an anti-PC(PM) response, we wanted to determine the molecular basis for this base change. A cDNA library derived from pre-immune splenic B cells was examined for the frequency of VDJ containing the A substitution at 95 and the presence of additional point mutations in these sequences. Six different cDNA were isolated which contained an A substitution at the VD junction (frequency 0.00009); a seventh positive cDNA could not be examined. The V segments of four of these cDNA matched known germline genes and were, therefore, unmutated. Two others closely matched V in families whose members have not all been characterized, hence, it is not known whether the mutations observed are somatic or germline in origin. Sequences of 35 cDNA clones, containing the same V segment but differing in D, J and junctional nucleotides, revealed no mutations. These results indicate that the A substitution generated at codon 95 is most likely a product of V-DJ joining.

Animals↗

Cell polarity and cell diversification during early mouse embryogenesis.

At the eight-cell stage of mouse development, the organization of blastomeres changes from radially symmetrical to polarized. This acquisition of cell polarity, followed by asymmetric divisions, leads to the formation of two phenotypically different cell types, which give rise to the first two cell lineages of the mouse blastocyst embryo, trophectoderm and the inner cell mass. Cell fate, controlled by positional information, is not irreversibly fixed during differentiation, providing the embryo with considerable developmental flexibility.

Animals↗

A theory of the ontogeny of the chicken humoral immune system: the consequences of diversification by gene hyperconversion and its extension to rabbit.

The immune system's repertoire is generated in two stages: Stage I results in a small size high copy number repertoire that is diversified by "mutation" to result in a large size low copy number repertoire referred to as Stage II. The Stage I or high copy number repertoire is derived from information stored directly in the genome by two mechanisms. (a) The copy-cassette mechanism: the Ig-locus has one rearrangeable V gene segment which acts as recipient for controlled gene conversion in cis from a set of donor V gene segments that results in a family of subunits, L and H. This is illustrated by the avian systems. (b) The cassette-exchange mechanism: the Ig-locus has many rearrangeable V gene segments which are fused into transcription units, the products of which are a family of L and H subunits identical in function to those resulting from the copy-cassette mechanism. This is illustrated by the murine or human systems. It is possible for a species to use both mechanisms, copy-cassette at one Ig locus and cassette-exchange at the other Ig locus. This seems to obtain in the rabbit system. Further, it is possible to encode the high copy number repertoire directly in the genome as tandemly repeated rearranged transcription units as one sees in shark (a genomic analogue of the cassette-exchange mechanism). We have discussed here and elsewhere (Cohn and Langman, 1990) the consequences of these mechanisms for haplotype exclusion and functional responsiveness to antigen. The Stage I or high copy number repertoire generated by any of the above mechanisms is now a substrate for "mutation" which generates the low copy number or Stage II repertoire. These three species are compared in table V. The high copy number repertoire is small but the response to any antigen that it recognizes is rapid. The low copy number repertoire is large but responsiveness to any antigen it recognizes is slow. Cooperativity between the two repertoires optimizes the overall responsiveness with respect to rapidity of response and range of responsiveness. The use of a copy-cassette mechanism requires that the phi B cell undergoing gene conversion have a single rearranged L- and H-chain haplotype (L+/oH+/o). The reason is that conversion can correct an aberrantly rearranged transcription unit and generate an unacceptable level of doubles. In order to have one chromosome functionally rearranged and the homologue in the germline configuration, a selection mechanism is required.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Diversification of cell cycle controls in developing embryos.

During embryogenesis, a genetic program coordinates cell proliferation with morphogenesis and cell differentiation. Recent studies using Drosophila have shown how, as development proceeds, this program directs different cell types to acquire unique modes of cell cycle regulation. As maternal cell cycle factors are exhausted and replaced by differentially expressed zygotic factors, an increasing repertoire of gene products become potential regulators of the cycle. Cyclin B, Cdc25, and Cyclin E each act as limiting regulators in Drosophila in specific cell types at particular developmental stages. The genes encoding these and many other candidate regulators have been cloned from mice, but their roles in vivo have yet to be understood.

Animals↗

Homeotic genes and diversification of the insect body plan.

The homeotic genes regulate segmental identity by repressing the formation of or influencing the morphology of segmental structures during development. The specific roles these genes have played in the generation of insect diversity are discussed relative to abdominal limb formation and to the evolution of wings as novel repeated structures. Other recent findings discussed suggest possible 'homeotic' origins for the non-homeotic genes found within the homeotic complexes of higher insects.

Animals↗

Myoblasts, myosins, MyoDs, and the diversification of muscle fibers.

Distinct types of muscle fibers form and become innervated by appropriate motor neurons during development. Though the activity pattern of the innervating motor neuron affects fiber type in the adult, it is now clear that innervation is not required for the initial formation of fast and slow muscle fibers during embryonic and fetal development. In addition, multiple types of intrinsically different myoblasts are found at different stages of development and motor neurons may preferentially innervate specific types of muscle fibers at relatively early stages of myogenesis. Thus, at least some of the information required for the formation of specific motor units must be carried by muscle cells. Cellular and molecular analyses of the multiple types of myoblasts, myosin heavy chain isoforms, and myogenesis regulating proteins of the MyoD family are leading to a new understanding of the events that choreograph the formation of fast and slow motor units.

Animals↗

Diversification and specialization of the bacterial cytoskeleton.

The past decade has witnessed the identification and characterization of bacterial homologs of the three major eukaryotic cytoskeletal families: actin, tubulin and intermediate filaments. These proteins play essential roles in organizing bacterial subcellular environments. Recently, the ParA/MinD superfamily has emerged as a new bacterial cytoskeletal class, and imaging studies hint at the existence of even more, as yet unidentified, cytoskeletal systems. Much as the cytoskeleton is used for different purposes in different eukaryotic cells, the specific identities, functions and regulatory mechanisms of cytoskeletal proteins can vary between different bacterial species. In addition, extensive cross-talk between bacterial cytoskeletal systems may represent an important mode of cytoskeletal regulation. These themes of diversity, species-specificity and crosstalk are emerging as central properties of cytoskeletal biology.

Actins↗

Axial patterning and diversification in the cnidaria predate the Hox system.

Across the animal kingdom, Hox genes are organized in clusters whose genomic organization reflects their central roles in patterning along the anterior/posterior (A/P) axis . While a cluster of Hox genes was present in the bilaterian common ancestor, the origins of this system remain unclear (cf. ). With new data for two representatives of the closest extant phylum to the Bilateria, the sea anemone Nematostella and the hydromedusa Eleutheria, we argue here that the Cnidaria predate the evolution of the Hox system. Although Hox-like genes are present in a range of cnidarians, many of these are paralogs and in neither Nematostella nor Eleutheria is an equivalent of the Hox cluster present. With the exception of independently duplicated genes, the cnidarian genes are unlinked and in several cases are flanked by non-Hox genes. Furthermore, the cnidarian genes are expressed in patterns that are inconsistent with the Hox paradigm. We conclude that the Cnidaria/Bilateria split occurred before a definitive Hox system developed. The spectacular variety in morphological and developmental characteristics shown by extant cnidarians demonstrates that there is no obligate link between the Hox system and morphological diversity in the animal kingdom and that a canonical Hox system is not mandatory for axial patterning.

Animals↗

The evolution and diversification of Dicers in plants.

Most multicellular organisms regulate developmental transitions by microRNAs, which are generated by an enzyme, Dicer. Insects and fungi have two Dicer-like genes, and many animals have only one, yet the plant, Arabidopsis, has four. Examining the poplar and rice genomes revealed that they contain five and six Dicer-like genes, respectively. Analysis of these genes suggests that plants require a basic set of four Dicer types which were present before the divergence of mono- and dicotyledonous plants ( approximately 200 million years ago), but after the divergence of plants from green algae. A fifth type of Dicer seems to have evolved in monocots.

Arabidopsis↗

Diversification of yeast proteins as an approach for the development of sustainable food systems.

Despite growing trend in sustainable protein sources, yeast proteins have mainly been explored as a source of bioactive peptides using a monospecies and general protein approach. The contribution of highly abundant protein fractions in the yeast proteome to peptide formation remains insufficiently investigated, limiting a comprehensive understanding of yeast proteins as optimized peptide sources. The current review presents a systematic analysis of yeast proteins as emerging protein sources and evaluates the suitability of high-abundance proteins as bioactive peptide precursors by in silico techniques. Moreover, brewery by-product and single-cell yeast protein approaches are compared in terms of composition and techno-functionality whereas peptide formation mechanisms (in situ and ex situ) and regulatory aspects for food applications are also addressed. Cytoplasmic metabolic proteins, particularly glycolytic enzymes (GAPDH), are identified as highly abundant fractions of the yeast proteome. Proteins associated with cell and organelle membranes also contribute substantially based on cellular localization. These findings imply that such proteins may act as key precursors of yeast-derived bioactive peptides. In silico hydrolysis with Alcalase suggests a tendency toward the generation of short-chain peptides (3-11/14 aa), which may support biological activity. Moreover, peptide profiles appear to vary across yeast species, highlighting the role of species diversity in peptide generation. While single-cell yeast protein allows more controlled production than brewery by-products, nucleic acid content in both may limit applications. Overall, yeast proteins appear to be metabolically adaptable and species-diverse sources for various biological peptides.

Saccharomyces cerevisiae↗