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The human SB1.8 gene (DXS423E) encodes a putative chromosome segregation protein conserved in lower eukaryotes and prokaryotes.

We report that the human gene SB1.8 (DXS423E) encodes a protein of 1233 amino acids that is highly homologous (30% identity) to the essential yeast protein SMC1 which is required for the segregation of chromosomes at mitosis. Both SB1.8 and SMC1 contain an N-terminal NTP binding site, a central coiled-coil region and a C-terminal helix-loop-helix domain, and have structural features in common with the force generating proteins myosin and kinesin. SB1.8 also exhibits regions of homology and overall structural similarity to the prokaryote (Mycoplasma hyorhinis) protein 115p. Thus SB1.8 and SMC1 are members of a highly conserved and ubiquitous family of proteins that appear to have a fundamental role in cell division. In addition we show that SB1.8 (DXS423E) maps to a cosmid contig that lies centromeric to the OATL2 locus at chromosome Xp11.2.

Amino Acid Sequence↗

Mitochondria: potential roles in embryogenesis and nucleocytoplasmic transfer.

This review examines current understanding of mammalian mitochondria and mitochondrial DNA in the light of new reproductive technologies. Mitochondria are central to ageing, apoptosis, metabolism and many diseases. They are controlled by a dual genome system, with cooperation between endogenous mitochondrial genes and mitochondrial genes translocated to the nucleus over the course of evolution. This translocation has been accompanied by extreme compression of the mitochondrial genome, with little tolerance for mutations or heteroplasmy (multiple genomes). The highly compact mitochondrial genome appears to be maintained by a stringent numerical bottleneck in embryogenesis and oogenesis, followed by clonal expansion from a highly selected subset of precursor molecules. The dual nature of control between nucleus and cytoplasm sets up potential conflicts, which are normally resolved by natural selection. Such potentially opposing interests and mechanisms are probably partly to blame for the poor rates of success in cloning animals by nuclear transfer. The ability to construct cell systems and animal embryos with novel combinations and permutations of nuclear and cytoplasmic genes will provide powerful tools for examining these fundamental biological questions. Clinically, attempts to 'rescue' abnormal human oocytes or embryos by cytoplasmic transfer risk complex and unpredictable outcomes emerging from disharmonious nuclear-cytoplasmic interactions.

Aging↗

Mother guarding: how offspring may influence the extra-pair behaviour of their parents.

In this paper we propose a novel form of social control of mate choice. Through mother guarding, offspring can help in protecting the paternity of their father by preventing their mother from engaging in extra-pair matings. We present a model that predicts the circumstances under which mothers should be selected to seek or avoid extra-pair matings, and existing offspring should be selected to prevent or promote such matings. In its simplest form, our model shows that offspring are selected to mother guard as long as the viability of extra-pair young is less than twice that of within-pair young; when the relative viability is greater, offspring are selected to promote extra-pair mating by their mother. If the existing offspring are not necessarily sired by their mother's social mate, then the potential for conflict is further reduced. We also consider whether offspring have an interest in the extra-pair reproduction of their fathers. We show that when the costs of the father's infidelity to the mother's brood are high, existing offspring are selected to prevent extra-pair mating by their father; when such costs are low, offspring are selected to promote extra-pair mating by their father. In principle, our model applies to all species where offspring show delayed dispersal and where breeding pairs raise multiple broods or litters. This situation exists in, but is not limited to, the majority of cooperatively breeding species. The significance of this model with regard to our current understanding of the evolution of extra-pair behaviour in such species is discussed.

Animals↗

Our Community Hospital: the evolution of a rural primary care hospital.

In the next few years, Our Community Hospital, located in the small town of Scotland Neck, NC, will undergo a conversion through which it may serve as an appropriate model for similar small hospitals in distressed rural communities. With technical and grant assistance from the Office of Rural Health and Resource Development of the North Carolina Department of Human Resources, the hospital has begun to phase out almost all acute care services and will expand and strengthen its focus on primary care, emergency medical services, and services for elderly persons. This paper addresses four issues of greatest concern to hospital administrators, rural health professionals, academics, and rural residents interested in hospital conversions: (1) community involvement during the planning process; (2) the evolution of the program's structure; (3) financing for the project; and (4) the development of cooperation between state and federal governments, foundations, and private groups. This case study describes one possible course in addressing an acute health care problem facing rural America--the viability of rural hospitals.

Aged↗

Tracheal respiration in insects visualized with synchrotron x-ray imaging.

Insects are known to exchange respiratory gases in their system of tracheal tubes by using either diffusion or changes in internal pressure that are produced through body motion or hemolymph circulation. However, the inability to see inside living insects has limited our understanding of their respiration mechanisms. We used a synchrotron beam to obtain x-ray videos of living, breathing insects. Beetles, crickets, and ants exhibited rapid cycles of tracheal compression and expansion in the head and thorax. Body movements and hemolymph circulation cannot account for these cycles; therefore, our observations demonstrate a previously unknown mechanism of respiration in insects analogous to the inflation and deflation of vertebrate lungs.

Animals↗

Early allelic selection in maize as revealed by ancient DNA.

Maize was domesticated from teosinte, a wild grass, by approximately 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete.

Alleles↗

Analysis of gamma delta T cells in the chicken.

T cell development in birds and mammals is remarkably similar. One hallmark of these similarities is the division of T cells into two sublineages characterized by different T cell receptor (TCR) molecules--the gamma delta and alpha beta TCRs. These two sublineages differ in several ways besides the molecular form of the TCR, such as the mechanisms involved in TCR repertoire selection and their pattern of tissue localization. The extensive similarity between the avian and mammalian gamma delta T cells suggest that the separation of these two lineages is relatively ancient evolutionarily. The advantages of the avian system as a developmental model have allowed information to be obtained on the gamma delta T cells which may be of general relevance.

Animals↗

Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.

The engulfment of dying cells is a specialized form of phagocytosis that is extremely conserved across evolution. In the worm, it is genetically controlled by two parallel pathways, which are only partially reconstituted in mammals. We focused on the recapitulation of the CED-1 defined pathway in mammalian systems. We first explored and validated MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals and hence progressed toward the analysis of molecular interactions along the corresponding pathway. We ascertained that, in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a functional or a mutant ABCA1 exerted a transdominant positive or negative modulation on the MEGF10-dependent engulfment. The combined use of biochemical and biophysical approaches indicated that this functional cooperation relies on the alternate association of these receptors with a common partner, endogenously expressed in our cell system. We provide the first working model structuring in mammals the CED-1 dependent pathway.

ATP Binding Cassette Transporter 1↗

Human adaptability research into the beginning of the third millennium.

Human adaptability, as a field of inquiry within human biology, became defined during the research activities of the International Biological Program (IBP) (1964-1974). During this period, research was focused on ecological, physiological, and genetic studies of human populations within the theoretical frameworks of adaptation and evolution. Other defining characteristics of the IBP human adaptability research were standardization of methods, multidisciplinary projects, international cooperation, and a concern with human health issues. Some observers suggest that this research contributed to the ongoing transformation of physical anthropology and related fields from a largely descriptive to an analytical science. During the 25 years between the end of the IBP and the present, a number of research trends have continued: Several new multidisciplinary projects were initiated and completed; a subfield of demography within human biology has matured; nutrition, infant and child growth, and health studies have proliferated; and molecular genetics and DNA analysis have superseded the earlier population genetics. International programs today are geared toward more practical and applied studies with less emphasis on basic science. Continuation of human adaptability research into the 21st century is likely to make contributions in 3 broad areas: population, environment, and health. Productive research is likely to contribute to these 3 areas in the following categories: reproduction, psychosocial stress, life span approaches to health, effects of losses in biodiversity on health, a human biology of poverty, emerging infectious diseases, epidemiology of modernization, evolutionary medicine, and aging. The success of much of this research in its contribution to knowledge will come from the integrated perspectives of a biobehavioral framework of inquiry.

Adaptation, Physiological↗

Complex organization in multicellularity as a necessity in evolution.

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

Biological Evolution↗

Evolutionary conservation of antigen recognition: the chicken T-cell receptor beta chain.

T cells play important regulatory roles in the immune responses of vertebrates. Antigen-specific T-cell activation involves T-cell receptor (TCR) recognition of a peptide antigen presented by a major histocompatibility complex molecule, and much has been learned about this antigen-recognition process through structural and genetic studies of mammalian TCRs. Although previous studies have demonstrated that avian T cells express cell-surface molecules analogous to the mammalian TCR heterodimers, TCR genes have not been identified in nonmammalian species. We now report the cloning of a cDNA that encodes the beta chain of the chicken TCR. Southern blot analysis using this TCR beta cDNA probe demonstrated that the chicken TCR beta locus was clonally rear-ranged in chicken T-cell lines. TCR beta mRNA was expressed in cells isolated from the thymus but not in cells from the bursa of Fabricius where B cells are generated. Sequence analysis of six additional TCR beta cDNAs suggested the existence of at least two variable (V) region families, three joining (J) elements, and single diversity (D) and constant (C) elements. As in mammals, considerable nucleotide diversity was observed at the junctions of the variable, diversity, and joining elements in chicken TCR beta cDNAs. Genomic V beta and J beta elements were also cloned and sequenced. Both elements are flanked by classical heptamer/nonamer recombination signal sequences. Although the chicken and mammalian TCR beta chains displayed only 31% overall amino acid sequence identity, a number of conserved structural features were observed. These data indicate that (i) the chicken TCR beta repertoire is generated by combinatorial and junctional diversity and (ii) despite divergent evolution at the level of nucleotide sequence, important structural features of the TCR beta polypeptide are conserved between avian and mammalian species.

Amino Acid Sequence↗

Evolutionary cheating in Escherichia coli stationary phase cultures.

Starved cultures of Escherichia coli are highly dynamic, undergoing frequent population shifts. The shifts result from the spread of mutants able to grow under conditions that impose growth arrest on the ancestral population. To analyze competitive interactions underlying this dynamic we measured the survival of a typical mutant and the wild type during such population shifts. Here we show that the survival advantage of the mutant at any given time during a takeover is inversely dependent on its frequency in the population, its growth adversely affects the survival of the wild type, and its ability to survive in stationary phase at fixation is lower than that of its ancestor. These mutants do not enter, or exit early, the nondividing stationary-phase state, cooperatively maintained by the wild type. Thus they end up overrepresented as compared to their initial frequency at the onset of the stationary phase, and subsequently they increase disproportionately their contribution in terms of progeny to the succeeding generation in the next growth cycle, which is a case of evolutionary cheating. If analyzed through the game theory framework, these results might be explained by the prisoner's dilemma type of conflict, which predicts that selfish defection is favored over cooperation.

Cell Division↗

Novel role for prostaglandin E2 in fish hepatocytes: regulation of glucose metabolism.

Prostaglandin E(2) (PGE(2)) potently activated glycogenolysis and gluconeogenesis in isolated rockfish (Sebastes caurinus) hepatocytes. The average degree of activation for glycogenolysis was 6.4+/-0.67-fold (mean+/-S.E.M.; n=37), and could be as much as 19-fold. Analysis of dose-concentration relationships between glycogenolytic actions and PGE(2) concentrations yielded an EC(50) around 120 nM in hepatocyte suspensions and 2 nM for hepatocytes immobilized on perifusion columns. For the activation of gluconeogenesis (1.74+/-0.14-fold; n=10), the EC(50) for suspensions was 60 nM. Intracellular targets for PGE(2) actions are adenylyl cyclase, protein kinase A and glycogen phosphorylase. Concentrations of cAMP increased with increasing concentrations of PGE(2), and peaked within 2 min of hormone application. In the presence of the phosphodiesterase inhibitor, isobutyl-3-methylxanthine, peak height was increased and peak duration extended. The protein kinase A inhibitor, Rp-cAMPS, counteracted the activation of glycogenolysis by PGE(2), implying that the adenylyl cyclase/protein kinase A pathway is the most important, if not exclusive, route of message transduction. PGE(2) activated plasma membrane adenylyl cyclase and hepatocyte glycogen phosphorylase in a dose-dependent manner. The effects were specific for PGE(2); smaller degrees of activation of glycogenolysis were noted for PGE(1), 11-deoxy PGE(1), 19-R-hydroxy-PGE(2), and prostaglandins of the A, B and Falpha-series. The selective EP(2)-receptor agonist, butaprost, was as effective as PGE(2), suggesting that rockfish liver contains prostaglandin receptors pharmacologically related to the EP(2) receptors of non-hepatic tissues of mammals. Rockfish hepatocytes quickly degraded added PGE(2) (t((1/2))=17-26 min). A similar ability to degrade PGE(2) has been noted in catfish (Ameiurus nebulosus) hepatocytes, but no glycogenolytic or gluconeogenic actions of the hormone are noted for this species. We conclude that PGE(2) is an important metabolic hormone in fish liver, with cAMP-mediated actions on glycogen and glucose metabolism, and probably other pathways regulated by cAMP and protein kinase A. The constant presence of EP(2)-like receptors is a unique feature of the fish liver, with interesting implications for function and evolution of prostaglandin receptors in vertebrates.

1-Methyl-3-isobutylxanthine↗