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Lamprey lymphocyte-like cells express homologs of genes involved in immunologically relevant activities of mammalian lymphocytes.

To shed light on the origin of adaptive immunity, a cDNA library was prepared from purified lymphocyte-like cells of a jawless vertebrate, the sea lamprey (Petromyzon marinus). Randomly selected cDNA clones were sequenced, and their homologies to proteins in the databases were determined. Of the sequences homologous to proteins involved in immune responses, five were selected for further characterization. Their encoding genes corresponded to loci that in jawed vertebrates are essential for activities of lymphocytes. These activities include regulation of T and B cell stimulation and proliferation (CD45); stabilization of molecular complexes involved in lymphocyte activation, adhesion, migration, and differentiation (CD9/CD81); adaptor functions in signaling leading to the activation of B lymphocytes (BCAP) and T lymphocytes (CAST); and amino acid transport associated with cell activation (CD98). The presence of these genes in the lamprey genome and their expression in lymphocyte-like cells support the notion that these cells perform many of the functions of gnathostome lymphocytes. It reopens the question of the stage jawless fishes reached in the evolution of their immune system.

Amino Acid Sequence↗

Evidence-based medicine in the dialysis unit: a few lessons from the USRDS and the NCDS and HEMO trials.

This short review argues for the importance of evidence-based medicine in the evolution of improved dialysis care. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has supported two major randomized clinical trials in dialysis, the National Cooperative Dialysis Study (NCDS), completed in 1981, and the Hemodialysis (HEMO) study, completed in 2002, and supports a major body of ongoing observational research through the U.S. Renal Data System (USRDS). The main results from the two randomized clinical trials and their implications for clinical practice and subsequent research are discussed here. The importance of observational research in the formulation of hypotheses and improvement of quality of care is examined. A brief historical perspective is provided on the critical examination of dialysis care in the late 1980s that occurred following completion of the NCDS. Finally, the rationale for continued investment in dialysis research and the plans of NIDDK to launch studies of more intensive dialysis regimens are discussed.

Evidence-Based Medicine↗

National library of medicine regional medical library program.

The National Library of Medicine is charged with the development and management of a National Biomedical Communications Network. The Regional Medical Library Program is a forerunner of such a network; the product and institutions involved will be critical elements in its evolution. The immediate objective of the RMLP, the facilitation of biomedical information transfer, presents a logistical problem requiring substantial commitment from the health sciences community and extensive cooperation among libraries in each region.

Journal Article↗

Control of abscission in agricultural crops and its physiological basis.

Some naphthalene and phenoxy compounds prevent preharvest drop of apples, pears, and citrus fruits. These studies have been complicated by an unrecognized high level of ethylene produced by leaves and fruit on trees sprayed with these growth regulators. An apparent contradiction is the effectiveness of both 2,4-dichlorophenoxyacetic acid and n-dimethylaminosuccinamic acid (a growth retardant which retards biosynthesis of auxin) in preventing abscission of apples. Thus, in the presence of low auxin concentrations in the tissue, this growth retardant prevents fruit abscission even more effectively than 2,4-dichlorophenoxyacetic acid at high auxin concentrations in the tissue. This anomaly is clarified on the basis that n-dimethylaminosuccinamic acid, in the presence of a known low ethylene biosynthesis, delays maturity of the fruit and thus prevents fruit abscission. On the other hand, 2,4-dichlorophenoxyacetic acid prevents abscission by direct growth hormone action, in spite of the side effects of ethylene production which speeds ripening of the fruit. With the promotion of abscission of leaves and fruit of agricultural crops, attention is given to the use of chemicals which induce ethylene production when applied to the plant, but which have no growth promotion effect to retard abscission. We can distinguish 5 kinds of such chemicals. One group includes gibberellic and abscisic acids that induce treated leaves to produce ethylene and abscise (under certain circumstances). However, they do not induce ethylene production by fruit and do not promote fruit abscission. A second group includes ascorbic acid, which, when used at relatively high levels, induces fruit to produce enough ethylene to promote abscission. Ascorbic acid-treated leaves also produce ethylene but not enough to cause much defoliation. A third group includes protein-synthesis inhibitors, such as cycloheximide. When low concentrations (about 30 mumoles/l) are sprayed on the fruit, the rapid effect of the freely moving ethylene (produced by the treated fruit) appears to mask temporarily any potential effect of the slowly moving inhibitor. A fourth group includes 2-chloroethylphosphonic and cupric ethylenediaminetetracetic acids, which induce ethylene production of fruit and leaves; production by leaves is substantially greater than by fruit and substantial defoliation results. A fifth group includes the cotton defoliation chemicals which clearly produce ethylene primarily as a result of chemical injury to the leaf blade. Another group of compounds, represented by beta-hydroxyethylhydrazine, produces ethylene by a chemical reaction with formaldehyde and water, and the presence of leaves or fruit is not required. At this time we are unaware of how chemicals in groups one to four act to promote ethylene evolution in leaves and fruit, but possible biological and chemical paths of ethylene production are discussed.

Journal Article↗

Hsp70 chaperone systems: diversity of cellular functions and mechanism of action.

Hsp70 chaperone systems play an essential role in the life cycle of many proteins not only in an hostile environment but also under normal growth conditions. In the course of evolution the diversification of functions was accompanied by an amplification of components of the Hsp70 system. Here strategies are reviewed how different Hsp70 systems work independently or cooperate with each other in a functional network to perform their housekeeping tasks even under stress conditions. We further discuss how co-chaperones which act as targeting factors regulate the cycle of substrate binding and release upon which the Hsp70 chaperone activity depends.

HSP70 Heat-Shock Proteins↗

Recent advances in noninvasive techniques to monitor hormone-behavior interactions.

This paper reviews recent advances in field endocrinology, a focus as well as a method in primatology and behavioral ecology that permits the examination of social behavior and life history through hormonal investigations in natural settings. Endocrine data complements the traditional behavioral data collected by field scientists by providing quantitative measures for the examination of adaptive tradeoffs, costs of social strategies, and reproductive and social significance of mating events. Further, investigations of the physiological mechanisms of reproductive constraint provide tests of the adaptive significance of reproductive skew in cooperative and competitive breeders. Hormone data also can provide insights into the costs of competition and aggression and the role of temperament in individual reproductive success and the evolution of social systems. New, noninvasive methods for the collection of this information have augmented and expanded field endocrinology through the use of techniques that do not require potentially confounding physical or physiological manipulations. Specifically, urine and fecal samples can be collected from free-ranging animals and contain gonadal and adrenal hormones that parallel profiles of serum hormones. Sampling, preservation, extraction, and assay methods for the analysis of excreted steroids are reviewed along with the species and questions to which these methods have been applied.

Animals↗

Molecular phylogenetics of the allodapine bee genus Braunsapis: A-T bias and heterogeneous substitution parameters.

Extreme AT bias in Hymenopteran mitochondrial genes have created difficulties for molecular phylogenetic analyses, especially for older divergences where multiple substitutions can erode signal. Heterogeneity in the evolutionary rates of different codon positions and different genes also appears to have been a major problem in resolving ancient divergences in allodapine bees. Here we examine the phylogeny of relatively recent divergences in the allodapine bee genus Braunsapis. We examined heterogeneity in nucleotide substitution parameters for one nuclear gene and codon positions in two mitochondrial genes, exploring various phylogenetic analyses for recovering relationships among species from Africa, Madagascar, southern Asia, and Australia. We explored maximum parsimony, maximum likelihood, Log determinant and Bayesian analyses. Broad topological features of best fit trees tended to be similar for equivalent data sets (e.g., total, or with 3rd mt positions excluded), regardless of the analytic method used (e.g., maximum likelihood or Bayesian). Analyses that used the total data set without modelling partitions separately gave unlikely results, indicating that the Malagasy species was most closely related to Australian species. However, analyses that excluded 3rd mitochondrial positions, or modelled partitions separately, suggested that the Malagasy species falls within the African clade. The unlikely topologies apparently result from long branch attraction, and this problem is ameliorated where modelling allows more realistic estimates of base composition and evolutionary rates for 3rd mitochondrial positions. However, we found that even when codon positions are modelled separately, estimated evolutionary rates for 3rd mitochondrial positions are likely to underestimate true rates. Long branch attraction and multiple substitutions are likely to be much more difficult to circumvent in analyses that explore older, generic-level, divergences in allodapine bees where overwriting is expected to be much more extreme. Our results indicate an African origin for Braunsapis, followed by a single, very early, dispersal event into Asia and then by a later dispersal event into Australia. The Malagasy species is derived from within the African clade.

Animals↗

Self/other organization in human psychological development.

Evidence from the evolution of human cultural behavior and learning, embryology and genetics of the brain, and the behavior of human infants indicates that the critical and uniquely human motives for cooperative imagination and joint interest in objects and tasks are determined by expression of genes and epigenetic neural systems elaboration long before birth, along with essential peripheral organs of perception and motor expression that will serve in communication by rhythmic facial, vocal, gestural, and body movement signals. These cerebral motives continue to exercise their influence on neural development and behavior throughout life, transforming the behaviors of the developing individual through a succession of phases to which other individuals and cultural institutions are constrained to adapt. We discuss the theory of innate intersubjectivity and relate it to the hypothesis of an Innate Motive Formation that emerges in brain development as regulator of morphogenesis in neural systems, and that continues to function, postnatally, as generator of motives and emotions by which human contacts and relationships are regulated. We suggest that differentiates of the primary motive formation in the embryo brain later serve to generate intelligent exploration of the objective environment and the emergence of an additional dialogic mechanism that represents the self-subject as a partner for an other-subject, intersubjectively. Intersubjective communication in infancy leads, through systematic age-related transformations of the brain and behavior, to preverbal mimetic negotiation of cooperative awareness and joint task performance. Finally we discuss, in relation to this theory, interpretations of faulty communication and development at different stages of the life cycle that result from maternal postnatal depression, autism, premature birth and schizophrenia.

Behavior↗

Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors.

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation-contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation-contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution.

Algorithms↗

Anaesthesia for awake craniotomy--evolution of a technique that facilitates awake neurological testing.

BACKGROUND: There is an increasing trend towards performing craniotomy awake. The challenge for the anaesthetist is to provide adequate analgesia and sedation, haemodynamic stability, and a safe airway, with an awake, cooperative patient for neurological testing. METHODS: The records of all patients who had awake craniotomy at our institution were reviewed. Patients were divided into three groups according to anaesthetic technique. Patients in Group 1 were sedated throughout the procedure. Patients in Groups 2 and 3 had an asleep-awake-asleep technique. Those in Group 2 were anaesthetized with a propofol infusion and fentanyl, and breathed spontaneously through a laryngeal mask airway (LMA). Patients in Group 3 had total i.v. anaesthesia with propofol and remifentanil, and ventilation was controlled using an LMA. We noted the incidence of complications in each group. RESULTS: There were 99 procedures carried out between 1989 and 2002. Group 3 had the fewest complications. No patients in Group 3 developed hypercapnia (E'(CO(2)) >6 kPa), compared with all of the patients in Group 2. Patients in Group 1 had no E'(CO(2)) monitoring, but 7% developed airway obstruction. No patients in Group 3 required additional analgesia for pain, compared with 70% of patients in Group 2. CONCLUSIONS: We have developed a technique for craniotomy, which facilitates awake neurological testing, is safe, and has good patient satisfaction.

Adolescent↗

AIDS: a role for host genes.

Suspicion that human genes affect the natural history of AIDS has been confirmed by discoveries of three such genes, one of which confers near-total immunity in about 1% of Caucasians. The findings suggest a novel therapeutic target: not HIV but the host's cooperation with it. They also herald an era in which genomes are seen as having been shaped by the evolutionary pressures of infection, and may thus hold evolution-tested therapies.

Acquired Immunodeficiency Syndrome↗

Mechanisms causing rapid and parallel losses of ribose catabolism in evolving populations of Escherichia coli B.

Twelve populations of Escherichia coli B all lost D-ribose catabolic function during 2,000 generations of evolution in glucose minimal medium. We sought to identify the population genetic processes and molecular genetic events that caused these rapid and parallel losses. Seven independent Rbs(-) mutants were isolated, and their competitive fitnesses were measured relative to that of their Rbs(+) progenitor. These Rbs(-) mutants were all about 1 to 2% more fit than the progenitor. A fluctuation test revealed an unusually high rate, about 5 x 10(-5) per cell generation, of mutation from Rbs(+) to Rbs(-), which contributed to rapid fixation. At the molecular level, the loss of ribose catabolic function involved the deletion of part or all of the ribose operon (rbs genes). The physical extent of the deletion varied between mutants, but each deletion was associated with an IS150 element located immediately upstream of the rbs operon. The deletions apparently involved transposition into various locations within the rbs operon; recombination between the new IS150 copy and the one upstream of the rbs operon then led to the deletion of the intervening sequence. To confirm that the beneficial fitness effect was caused by deletion of the rbs operon (and not some undetected mutation elsewhere), we used P1 transduction to restore the functional rbs operon to two Rbs(-) mutants, and we constructed another Rbs(-) strain by gene replacement with a deletion not involving IS150. All three of these new constructs confirmed that Rbs(-) mutants have a competitive advantage relative to their Rbs(+) counterparts in glucose minimal medium. The rapid and parallel evolutionary losses of ribose catabolic function thus involved both (i) an unusually high mutation rate, such that Rbs(-) mutants appeared repeatedly in all populations, and (ii) a selective advantage in glucose minimal medium that drove these mutants to fixation.

Adaptation, Physiological↗